In one comparison from a 2-by-2 factorial trial, over 12,000 participants with a mean baseline blood pressure of 138/82 mm Hg were assigned to candesartan plus hydrochlorothiazide or to placebo. At ...5.6 years, there was no between-group difference in the rates of cardiovascular events.
High blood pressure is the leading risk factor for cardiovascular disease globally
1
and affects more than 1 billion adults worldwide.
2
Observational studies involving persons without cardiovascular disease show a graded increase in risk at systolic blood-pressure levels above 115 mm Hg.
3
It has been suggested that lowering blood pressure at any level above this value will reduce the risk of cardiovascular events.
4
Antihypertensive therapy has been clearly shown to reduce the risk of cardiovascular disease among people with vascular or renal disease, diabetes, or hypertension with end-organ damage or, in the absence of these conditions, among persons with a systolic . . .
In a 2-by-2 factorial trial, 12,705 persons at intermediate risk were assigned to candesartan plus hydrochlorothiazide or placebo and to rosuvastatin or placebo. At 5.6 years, combination therapy ...resulted in a significantly lower risk of cardiovascular events than dual placebo.
Cardiovascular diseases are major causes of death and illness worldwide.
1
Both systolic blood pressure and low-density lipoprotein (LDL) cholesterol show graded associations with cardiovascular disease and together account for two thirds of the population-attributable risk of cardiovascular disease.
2
–
4
Therefore, combined lowering of LDL cholesterol and blood pressure can potentially have a bigger effect in reducing cardiovascular events than either intervention alone. Because the majority of cardiovascular events occur in persons at average risk with no previous cardiovascular disease, a strategy of broad population-based treatment of LDL cholesterol and blood pressure could be more effective than targeting only high-risk persons. . . .
Soil nematode communities and food web indices can inform about the complexity, nutrient flows and decomposition pathways of soil food webs, reflecting soil quality. Relative abundance of nematode ...feeding and life‐history groups are used for calculating food web indices, i.e., maturity index (MI), enrichment index (EI), structure index (SI) and channel index (CI). Molecular methods to study nematode communities potentially offer advantages compared to traditional methods in terms of resolution, throughput, cost and time. In spite of such advantages, molecular data have not often been adopted so far to assess the effects of soil management on nematode communities and to calculate these food web indices. Here, we used high‐throughput amplicon sequencing to investigate the effects of tillage (conventional vs. reduced) and organic matter addition (low vs. high) on nematode communities and food web indices in 10 European long‐term field experiments and we assessed the relationship between nematode communities and soil parameters. We found that nematode communities were more strongly affected by tillage than by organic matter addition. Compared to conventional tillage, reduced tillage increased nematode diversity (23% higher Shannon diversity index), nematode community stability (12% higher MI), structure (24% higher SI), and the fungal decomposition channel (59% higher CI), and also the number of herbivorous nematodes (70% higher). Total and labile organic carbon, available K and microbial parameters explained nematode community structure. Our findings show that nematode communities are sensitive indicators of soil quality and that molecular profiling of nematode communities has the potential to reveal the effects of soil management on soil quality.
Genetic Evaluation of Short Stature Dauber, Andrew; Rosenfeld, Ron G; Hirschhorn, Joel N
The journal of clinical endocrinology and metabolism,
09/2014, Letnik:
99, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Context:
Genetics plays a major role in determining an individual's height. Although there are many monogenic disorders that lead to perturbations in growth and result in short stature, there is ...still no consensus as to the role that genetic diagnostics should play in the evaluation of a child with short stature.
Evidence Acquisition:
A search of PubMed was performed, focusing on the genetic diagnosis of short stature as well as on specific diagnostic subgroups included in this article. Consensus guidelines were reviewed.
Evidence Synthesis:
There are a multitude of rare genetic causes of severe short stature. There is no high-quality evidence to define the optimal approach to the genetic evaluation of short stature. We review genetic etiologies of a number of diagnostic subgroups and propose an algorithm for genetic testing based on these subgroups.
Conclusion:
Advances in genomic technologies are revolutionizing the diagnostic approach to short stature. Endocrinologists must become facile with the use of genetic testing in order to identify the various monogenic disorders that present with short stature.
Soil organisms are a crucial part of the terrestrial biosphere. Despite their importance for ecosystem functioning, few quantitative, spatially explicit models of the active belowground community ...currently exist. In particular, nematodes are the most abundant animals on Earth, filling all trophic levels in the soil food web. Here we use 6,759 georeferenced samples to generate a mechanistic understanding of the patterns of the global abundance of nematodes in the soil and the composition of their functional groups. The resulting maps show that 4.4 ± 0.64 × 10
nematodes (with a total biomass of approximately 0.3 gigatonnes) inhabit surface soils across the world, with higher abundances in sub-Arctic regions (38% of total) than in temperate (24%) or tropical (21%) regions. Regional variations in these global trends also provide insights into local patterns of soil fertility and functioning. These high-resolution models provide the first steps towards representing soil ecological processes in global biogeochemical models and will enable the prediction of elemental cycling under current and future climate scenarios.
Cleft lip and palate Mossey, Peter A, Prof; Little, Julian, Prof; Munger, Ron G, Prof ...
The Lancet (British edition),
11/2009, Letnik:
374, Številka:
9703
Journal Article
Recenzirano
Summary Clefts of the lip and palate are generally divided into two groups, isolated cleft palate and cleft lip with or without cleft palate, representing a heterogeneous group of disorders affecting ...the lips and oral cavity. These defects arise in about 1·7 per 1000 liveborn babies, with ethnic and geographic variation. Effects on speech, hearing, appearance, and psychology can lead to longlasting adverse outcomes for health and social integration. Typically, children with these disorders need multidisciplinary care from birth to adulthood and have higher morbidity and mortality throughout life than do unaffected individuals. This Seminar describes embryological developmental processes, epidemiology, known environmental and genetic risk factors, and their interaction. Although access to care has increased in recent years, especially in developing countries, quality of care still varies substantially. Prevention is the ultimate objective for clefts of the lip and palate, and a prerequisite of this aim is to elucidate causes of the disorders. Technological advances and international collaborations have yielded some successes.
The growth hormone (GH)-insulin-like growth factor (IGF) cascade is central to the regulation of growth and metabolism. This article focuses on the history of the components of the IGF system, with ...an emphasis on the peptide hormones, IGF-I and -II, their cell surface receptors, and the IGF binding proteins (IGFBPs) and IGFBP proteases that regulate the availability of the peptide hormones for interaction with their receptors in relevant target tissues. We describe landmark events in the evolution of the somatomedin hypothesis, including evidence that has become available from experiments at the molecular and cellular levels, whole animal and tissue-specific gene knockouts, studies of cancer epidemiology, identification of prismatic human cases, and short- and long-term clinical trials of IGF-I therapy in humans. In addition, this new evidence has expanded our clinical definition of GH insensitivity (GHI) beyond growth hormone receptor mutations (classic Laron syndrome) to include conditions that cause primary IGF deficiency by impacting post-receptor signal transduction, IGF production, IGF availability to interact with the IGF-I receptor (IGF-1R), and defects in the IGF-1R, itself. We also discuss the clinical aspects of IGFs, from their description as insulin-like activity, to the use of IGF-I in the diagnosis and treatment of GH deficiency, and to the use of recombinant human IGF-I for therapy of children with GHI.
Children with skeletal dysplasias have not been consistently managed by pediatric endocrinologists despite the recognized expertise of these practitioners in managing genetic growth disorders. ...Growth-altering treatments have broadened the role of the pediatric endocrinologist to manage and sometimes become primary coordinators for genetic disorders such as Turner syndrome and Prader-Willi syndrome. We illustrate how recent advances in understanding the pathophysiology of skeletal disorders and the development of targeted treatments provide an opportunity for pediatric endocrinologists to further expand their role in managing certain skeletal dysplasias, including achondroplasia.
The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the ...invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.
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