A Review of the Adverse Effects of Peripheral Alpha-1 Antagonists in Hypertension Therapy

BACKGROUND: Doxazosin and its role as an antihypertensive agent have come under recent scrutiny as a result of the early termination of that treatment arm in ALLHAT. It is unclear why the cardiovascular (CV) event rate in this randomized, controlled trial (RCT), especially heart failure, is higher in those treated with a doxazosin-based regimen than with a chlorthalidone based-regimen. There has been little work in the past to summarize information on peripheral alpha-1 antagonists that may be helpful in evaluating the results of this randomized controlled trial. METHODS: Using Medline and the Cochrane databases, we performed a comprehensive review of the literature on the use of peripheral alpha-1 antagonists as antihypertensive agents, focusing on available information that could explain the excess cardiovascular events observed in the Antihypertensive and Lipid-Lowering Treatment to prevent Heart Attack Trial (ALLHAT). RESULTS: Minimal data were available concerning the effects of peripheral alpha-1 antagonists on CV endpoints. A multitude of short-term studies-ranging from small observational studies to short-term moderate-sized RCTs – focused on safety, efficacy, and tolerability, and some studies investigated the physiologic effects of these agents. These previously reported studies reveal associations with weight gain, fluid retention, and neurohormonal changes among various populations of those treated with peripheral alpha-1 antagonists. CONCLUSION: These findings suggest several possible mechanisms by which doxazosin may be inferior to low-dose diuretics as antihypertensive therapy for the prevention of heart failure

The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Reliability of the automatic procedures for locating earthquakes in southwestern Alps and northern Apennines (Italy)

International audienceReliable automatic procedure for locating earthquake in quasi-real time is strongly needed for seismic warning system, earthquake preparedness, and producing shaking maps. The reliability of an automatic location algorithm is influenced by several factors such as errors in picking seismic phases, network geometry, and velocity model uncertainties. The main purpose of this work is to investigate the performances of different automatic procedures to choose the most suitable one to be applied for the quasi-real-time earthquake locations in northwestern Italy. The reliability of two automatic-picking algorithms (one based on the Characteristic Function (CF) analysis, CF picker, and the other one based on the Akaike's information criterion (AIC), AIC picker) and two location methods (“Hypoellipse” and “NonLinLoc” codes) is analysed by comparing the automatically determined hypocentral coordinates with reference ones. Reference locations are computed by the “Hypoellipse” code considering manually revised data and tested using quarry blasts. The comparison is made on a dataset composed by 575 seismic events for the period 2000–2007 as recorded by the Regional Seismic network of Northwestern Italy. For P phases, similar results, in terms of both amount of detected picks and magnitude of travel time differences with respect to manual picks, are obtained applying the AIC and the CF picker; on the contrary, for S phases, the AIC picker seems to provide a significant greater number of readings than the CF picker. Furthermore, the “NonLinLoc” software (applied to a 3D velocity model) is proved to be more reliable than the “Hypoellipse” code (applied to layered 1D velocity models), leading to more reliable automatic locations also when outliers (wrong picks) are present

How do Local Earthquake Tomography and inverted dataset affect earthquake locations? The case study of High Agri Valley (Southern Italy)

Local earthquake tomography allows to both image the subsurface elastic properties of an area and to locate earthquakes. In this work, we discuss the choice of best parameterization in a tomographic model and the influence of retrieved velocity models on the accuracy of earthquake location in the High Agri Valley, southern Italy. The tomographic inversions were carried out with two datasets (dataset A and dataset B). Dataset B was obtained by integrating in the dataset A the data recorded by a very dense seismic network deployed around a specific cluster of seismicity. Velocity models obtained from the inversion of the two datasets are characterized by the same parameterization. However, the anomalies retrieved by the inversion of the second dataset look more reliable, based on results of checkerboard test. The retrieved 3D velocity model contributed to improve the accuracy of earthquake locations with respect to the 1D model. Data recorded by a very dense network in dataset B further contributed to reduce the errors and to improve the clustering of hypocentral positions of the best azimuthally covered cluster of seismicity. The importance of a 3D velocity model and of a proper network geometry for earthquake location is therefore demonstrated

2017 European guidelines for the management of genital herpes

Abstract: Genital herpes is one of the commonest sexually transmitted infections worldwide. Using the best available evidence, this guideline recommends strategies for diagnosis, management, and follow-up of the condition as well as for minimising transmission. Early recognition and initiation of therapy is key and may reduce the duration of illness or avoid hospitalisation with complications, including urinary retention, meningism, or severe systemic illness. The guideline covers a range of common clinical scenarios, such as recurrent genital herpes, infection during pregnancy, and co-infection with human immunodeficiency virus