Parathyroid hormone-related protein as a renal regulating factor: From Vessels to Glomeruli and Tubular Epithelium

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) produce similar biological effects through the PTH/PTHrP receptor. Less is known about the physiological role of PTHrP, which was first identified as the agent of the humoral hypercalcemia of malignancy. Despite the widespread production of PTHrP in healthy individuals, the concentration of the protein is below the detectable limit of current assays, suggesting that PTHrP normally functions locally in an autocrine or paracrine manner. Thus, some differences in their biological activities have been described and they may be related to the presence of different receptors. In this regard, a second receptor that binds selectively to PTH has also been found. Recent studies have demonstrated the expression of both PTH/PTHrP receptor and protein in the renal glomeruli. Moreover, there are convincing data that support a direct role of PTH and PTHrP in modulating renal blood flow and glomerular filtration rate. This multifunctional protein, PSHrP, also has a proliferative effect on both glomerular mesangial cells and tubular epithelial cells. Increases in the expression of PTHrP have been observed in several experimental models of nephropathies, suggesting that PTHrP upregulation is a common event associated with the mechanism of renal injury and repair

Normal reference values of strength in pelvic floor muscle of women: a descriptive and inferential study

Background: To describe the clinical, functional and quality of life characteristics in women with Stress Urinary Incontinence (SUI). In addition, to analyse the relationship between the variables reported by the patients and those informed by the clinicians, and the relationship between instrumented variables and the manual pelvic floor strength assessment.Methods: Two hundred and eighteen women participated in this observational, analytical study. An interview about Urinary Incontinence and the quality of life questionnaires (EuroQoL-5D and SF-12) were developed as outcomes reported by the patients. Manual muscle testing and perineometry as outcomes informed by the clinician were assessed. Descriptive and correlation analysis were carried out.Results: The average age of the subjects was (39.93 ± 12.27 years), (24.49 ± 3.54 BMI). The strength evaluated by manual testing of the right levator ani muscles was 7.79 ± 2.88, the strength of left levator ani muscles was 7.51 ± 2.91 and the strength assessed with the perineometer was 7.64 ± 2.55. A positive correlation was found between manual muscle testing and perineometry of the pelvic floor muscles (p < .001). No correlation was found between outcomes of quality of life reported by the patients and outcomes of functional capacity informed by the physiotherapist.Conclusion: A stratification of the strength of pelvic floor muscles in a normal distribution of a large sample of women with SUI was done, which provided the clinic with a baseline. There is a relationship between the strength of the pelvic muscles assessed manually and that obtained by a perineometer in women with SUI. There was no relationship between these values of strength and quality of life perceived

Cost-effectiveness analysis of antimuscarinics in the treatment of patients with overactive bladder in Spain: A decision-tree model

<p>Abstract</p> <p>Background</p> <p>Fesoterodine, a new once daily antimuscarinic, has proven to be an effective, safe, and well-tolerated treatment in patients with overactive bladder (OAB). To date, no analysis has evaluated the economic costs and benefits associated with fesoterodine, compared to antimuscarinics in Spain. The purpose of this analysis was to assess the economic value of OAB treatment with fesoterodine relative to extended release tolterodine and solifenacin, from the societal perspective.</p> <p>Methods</p> <p>The economic model was based on data from two 12-week, randomized, double-blind, and multicenter trials comparing fesoterodine and tolterodine extended released (ER). Treatment response rates for solifenacin were extracted from the published literature. Discontinuation and efficacy were based on the results of a 12-week multinational randomized clinical trial extrapolated to 52 weeks. Changes in health related quality of life were assessed with the King's Health Questionnaire, which was transformed into preference-based utility values. Medical costs included (expressed in € 2010) were antimuscarinics, physician visits, laboratory tests, incontinence pads and the costs of OAB-related comorbidities, fractures, skin infections, urinary tract infections, depression, and nursing home admissions associated with incontinence. Time lost from work was also considered. Univariate sensitivity analyses were also performed.</p> <p>Results</p> <p>At week 12, continents accounted for 50.6%, 40.6% and 47.2% of patients in the fesoterodine, tolterodine, and solifenacin groups, respectively. By week 52, the projected proportions of patients remaining on therapy were 33.1%, 26.5% and 30.8%, respectively. The projected quality- adjusted life years (QALY) gain (compared to baseline) over the 52-week simulation period were 0.01014, 0.00846 and 0.00957, respectively. The overall treatment cost was estimated at €1,937, €2,089 and €1,960 for fesoterodine, tolterodine and solifenacin, respectively. Therefore, treatment with fesoterodine resulted in similar overall costs and greater QALY gain than treatment with either tolterodine or solifenacin. Sensitivity analysis showed that these results were robust to all changes performed.</p> <p>Conclusions</p> <p>The results of this economic analysis suggest that fesoterodine is a cost-effective alternative to tolterodine and solifenacin for the treatment of patients with OAB in Spain. Fesoterodine provides additional health benefits while maintain a similar level of costs being a cost-effective treatment strategy from a societal perspective.</p

Characterization of the interface between highly conductive Ga:ZnO films and the silicon substrate

Gallium-doped zinc oxide films are an interesting alternative for transparent conductive materials. To improve their performance, the interface between the grown layer and the substrate must be fully understood. Accordingly, ZnO and Ga:ZnO films have been deposited onto p-type doped Si (111) substrates by magnetron sputtering for 1, 2, 3 and 20 min and their interfaces characterized by transmission electron microscopy, photoelectron spectroscopy, spectroscopic ellipsometry and impedance spectroscopy. The combination of transmission electron microscopy techniques suggested a more complex interface chemistry in the Ga:ZnO/Si case, a point confirmed by x-ray photoelectron spectroscopy measurements on very thin films. While the ZnO/Si interface consists mostly of silicon oxides, zinc silicates and some Zn0, the Ga:ZnO/Si interface, besides these constituents, has a noticeable amount of Ga:ZnO and small quantities of Ga0. The band alignment deduced from the photoelectron spectroscopy measurements, together with the layers and Si band gap values, evidences a higher work function for the doped film and a smaller conduction band barrier for the Ga:ZnO/Si interface. Concerning the optical and electrical characteristics, spectroscopic ellipsometry revealed no significant differences between the two interfaces, while impedance spectroscopy measurements demonstrated that the Ga:ZnO/Si interface is less resistive than the ZnO/Si one.Authors gratefully acknowledge financial support from the Spanish Ministerio de Economía & Competitividad (MINECO) and E.U. FEDER funds through the projects FUNCOAT-CSD2008-00023-CONSOLIDER INGENIO, TEC2014-53906-R, TEC2014-54260-C3-3-P, RYC-2010-06711 and MAT2014-57547-R, and from the Junta de Andalucía (FQM-192)

Impact of an enhanced screening program on the detection of non-AIDS neoplasias in patients with human immunodeficiency virus infection

Background: The incidence of non-AIDS defining cancer (NADC) is higher in people living with HIV (PLWH) than in the general population, and it is already one of the leading causes of death in the HIV-infected population. It is estimated that the situation will be aggravated by the progressive aging of PLWH. Early diagnosis through intensive cancer screening may improve the ability for therapeutic interventions and could be critical in reducing mortality, but it might also increase expenditure and harms associated with adverse events. The aim of this study is to evaluate an enhanced screening program for early diagnosis of cancer in PLWH compared to standard practice. The specific objectives are (1) to compare the frequency of cancer diagnosed at an early stage, (2) to analyze safety of the enhanced program: adverse events and unnecessary interventions, (3) to analyze the cost-utility of the program, and (4) to estimate the overall and site-specific incidence of NADC in PLWH. Methods: We will conduct a multicenter, non-blinded, randomized, controlled trial, comparing two parallel arms: conventional vs enhanced screening. Data will be recorded in an electronic data collection notebook. Conventional intervention group will follow the standard of care screening in the participating centers, according to the European AIDS Clinical Society recommendations, and the enhanced intervention group will follow an expanded screening aimed to early detection of lung, liver, anal, cervical, breast, prostate, colorectal, and skin cancer. The trial will be conducted within the framework of the Spanish AIDS Research Network Cohort (CoRIS). Discussion: The trial will evaluate the efficacy, safety, and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard of care practice. The information provided will be relevant since there are currently no studies on expanded cancer screening strategies in patients with HIV, and available data estimating cost effectiveness or cost-utility of such as programs are scarce. An enhanced program for NADC screening in patients with HIV could lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions, but it is critical to demonstrate that the benefits clearly outweigh the harms, before the strategy could be implemented

Role of surface chemistry on electric double layer capacitance of carbon materials

A large number of porous carbon materials with different properties in terms of porosity, surface chemistry and electrical conductivity, were prepared and systematically studied as electric double layer capacitors in aqueous medium with H2SO4 as electrolyte. The precursors used are an anthracite, general purpose carbon fibres and high performance carbon fibres, which were activated by KOH, NaOH, CO2 and steam at different conditions. Among all of them, an activated anthracite with a BET surface area close to 1500 m2/g, presents the best performance, reaching a value of 320 F/g, using a three-electrode system. The results obtained for all the samples, agree with the well-known relationship between capacitance and porosity, and show that the CO-type oxygen groups have a positive contribution to the capacitance. A very good correlation between the specific capacitance and this type of oxygen groups has been found.The authors thank MEC for financial support (Project PPQ2003-03884)

Nanostructural changes upon substitutional Al doping in ZnO sputtered films

Al:ZnO layers, with low and high Al content, 0.2% and 2.1% cat. respectively, have been prepared using the RF magnetron sputtering technique. Noticeable differences in the optical and electrical properties have been detected in these films. With doping, the resistivity decreases and the band-gap increases. The alterations in the films crystalline structure are explained in terms of the nanostructural changes induced by Al substitutional doping, such as a higher concentration of edge dislocation defects and a higher rotation of crystalline nanodomains in the plane of the films (normal to the preferential orientation c-axis) for the high content Al:ZnO layer. A complete description of such effects has been accomplished using several characterization techniques, such as X-ray diffraction, Raman spectroscopy and transmission electron microscopy. The combination of these techniques provides an exhaustive understanding of the films nanostructure