Effect of LHRH analogs on lower urinary tract symptoms associated with advanced prostate cancer in real clinical practice : ANALUTS study

To estimate the prevalence of lower urinary tract symptoms (LUTS) in patients with prostate cancer scheduled to receive LHRH analogs, and to assess the effectiveness of LHRH analogs on LUTS in patients presenting moderate/severe symptoms. Prospective, noninterventional, multicenter study conducted at 28 centers in Spain and Portugal. LUTS were evaluated using the International Prostate Symptom Score (IPSS) at baseline, 24 and 48 weeks after initiation of treatment. Subanalyses were performed according to age and concomitant treatment (radiotherapy, alpha-blockers, and antiandrogens). A total of 354 patients were treated with LHRH analogs for 48 weeks. The percentage of patients with moderate/severe LUTS (IPSS > 7) decreased from 60.2% (n = 213/354) at baseline to 52.8% (n = 187/354) at Week 48. Among patients with moderate/severe LUTS at baseline: 73.7% (n = 157/213) still had moderate/severe LUTS at Week 48; percentage reductions of patients with LUTS at Week 48 were statistically significant (p < 0.05) overall and by age or concomitant treatment, except for alpha-blockers (84.2% patients receiving them still had moderate/severe LUTS at Week 48). All IPSS items, including quality of life for urinary symptoms, improved throughout the study. The only predictor of response to treatment with LHRH analogs that improved IPSS by 3 points after 48 weeks was baseline testosterone levels. Lower baseline testosterone levels were associated with greater improvement in IPSS after treatment with LHRH analogs (odds ratio 0.998, 95% confidence interval 0.996-1.000, p = 0.0277). LHRH analogs have a positive effect in patients with locally advanced or metastatic prostate cancer presenting moderate/severe LUTS regardless of age or concomitant treatment received (radiotherapy, antiandrogens, or alpha-blockers)

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

The AMPK Family Member Snf1 Protects <em>Saccharomyces cerevisiae</em> Cells upon Glutathione Oxidation

<div><p>The AMPK/Snf1 kinase has a central role in carbon metabolism homeostasis in <i>Saccharomyces cerevisiae</i>. In this study, we show that Snf1 activity, which requires phosphorylation of the Thr210 residue, is needed for protection against selenite toxicity. Such protection involves the Elm1 kinase, which acts upstream of Snf1 to activate it. Basal Snf1 activity is sufficient for the defense against selenite, although Snf1 Thr210 phosphorylation levels become increased at advanced treatment times, probably by inhibition of the Snf1 dephosphorylation function of the Reg1 phosphatase. Contrary to glucose deprivation, Snf1 remains cytosolic during selenite treatment, and the protective function of the kinase does not require its known nuclear effectors. Upon selenite treatment, a null <i>snf1</i> mutant displays higher levels of oxidized versus reduced glutathione compared to wild type cells, and its hypersensitivity to the agent is rescued by overexpression of the glutathione reductase gene <i>GLR1.</i> In the presence of agents such as diethyl maleate or diamide, which cause alterations in glutathione redox homeostasis by increasing the levels of oxidized glutathione, yeast cells also require Snf1 in an Elm1-dependent manner for growth. These observations demonstrate a role of Snf1 to protect yeast cells in situations where glutathione-dependent redox homeostasis is altered to a more oxidant intracellular environment and associates AMPK to responses against oxidative stress.</p> </div

Effect of selenite on growth in low or normal phosphate conditions.

<p>Relative growth of wild type (W303-1A), <i>Δsnf1</i> (Wsnf1), <i>Δpho84</i> (MML1304) and <i>Δsnf1Δpho84</i> (MML1401) cells in low or normal phosphate medium without or with 3 mM selenite. Growth in shaken microtiter plates was automatically recorded and the growth values reached by each strain after 24 hours were made relative to the growth of wild type cells, which was given the unit value for each growth condition considered. The mean of three independent experiments (± s.d.) is represented. Note that different scales of the <i>y-</i>axis are employed in both panels.</p

Protection against selenite toxicity does not require activity of the known nuclear effectors of Snf1.

<p>(<b>A</b>) Localization of Snf1 upon different treatments. The Snf1-GFP protein expressed in pOV84-transformed wild type cells was visualized by fluorescence microscopy in cells growing in SC medium without treatment (Glucose) or after 2 hours treatment with 4 mM sodium selenite or 1 mM DEM. In parallel, cell samples were shifted to YPGly and observed one hour later (Glycerol). Prior to observations, samples were stained with Hoesch for nuclei localization. The corresponding phase contrast fields (PC) are shown. (<b>B</b>) Growth assays of serial dilutions of the following strains on YPD medium with sodium selenite: wild type (W303-1A), <i>Δsnf1</i> (Wsnf1), <i>Δcat8</i> (MML1417), <i>Δmig1</i> (MML1408), <i>Δsip4</i> (MML1396) and <i>Δadr1</i> (MML1419). (<b>C</b>) Localization of HA-Mig1 upon different treatments. Cells transformed with pHA-Mig1 were grown in SC medium and treated with selenite for the indicated times or shifted to medium with 2% galactose instead of glucose. Cells were observed by immunofluorescence experiments with anti-HA antibodies, with parallel nuclear staining with DAPI. (<b>D</b>) Northern blot expression analysis of the indicated genes in wild type (W303-1A) cells growing in YPD medium without (Glucose) or with selenite for the indicated times (hours), or in YPGal medium (Galactose) for 1 hour. <i>SNR19</i> was employed as loading control. The same blotted membrane was successively hybridized with the three probes after extensive washings.</p

Strains employed in this study.

<p>Strains employed in this study.</p

Protection against selenite preferentially requires the Elm1 kinase.

<p>(<b>A</b>) Growth assays of serial dilutions of the following strains on YPD medium with sodium selenite: wild type (W303-1A), <i>Δsnf1</i> (Wsnf1), <i>Δsak1</i> (MML1370), <i>Δelm1</i> (YPDahl21), <i>Δtos3</i> (YPDahl19), <i>Δsak1Δelm1</i> (MML1387), <i>Δsak1Δtos3</i> (MML1389), <i>Δelm1Δtos3</i> (MML1390) and <i>Δsak1Δelm1Δtos3</i> (MML1392). (<b>B</b>) As in (A) with the strains: wild type, <i>Δsnf1</i>, <i>Δelm1</i> and <i>Δsnf1Δelm1</i> (MML1724).</p

Snf1 is required for protection against glutathione-oxidizing agents.

<p>(<b>A</b>) Growth assays of serial dilutions of the following strains on YPD medium with DEM, diamide or <i>t</i>-BOOH: wild type (W303-1A), <i>Δsnf1</i> (Wsnf1) and <i>Δsip1Δsip2Δgal83</i> (MML1459). (<b>B</b>) Growth assays of serial dilutions of the following strains, plated on SC medium with DEM: wild type (W303-1A) and <i>Δsnf1</i> (Wsnf1) cells transformed with vector pWS93, and <i>Δsnf1</i> cells transformed with pWS-Snf1, pWS-Snf1-T210A and pWS-Snf1-K84R. (<b>C</b>) Growth assays of serial dilutions of the following strains on YPD medium with DEM: wild type (W303-1A), <i>Δsak1Δelm1</i> (MML1387), <i>Δsak1Δtos3</i> (MML1389), <i>Δelm1Δtos3</i> (MML1390) and <i>Δsak1Δelm1Δtos3</i> (MML1392). (<b>D</b>) Western blot analysis of Thr210-phosphorylated Snf1 (Snf1-P) and of total Snf1. The same membrane was successively hybridized with the corresponding antibodies. Samples were from wild type (W303-1A) exponential cultures in YPD treated with DEM or diamide. Control samples were from YPD-grown wild type cells shifted for 1 hour to YPGly (-Glu). (<b>E</b>) Growth assays of wild type (W303-1A) and <i>Δsnf1</i> (Wsnf1) cells transformed with multicopy vector YEplac195 or its derivative P1116 overexpressing <i>GLR1</i>, in SC medium with DEM.</p

Phosphorylation levels of Snf1 at Thr210 do not correlate with protection against selenite treatment.

<p>(<b>A</b>) Western blot analysis of phosphorylated Snf1 at Thr210 with anti-phospho-Thr172-AMPK (upper panel). Blots were rehybridized with anti-Snf1 antibodies for total Snf1 (lower panel). Samples were obtained from wild type (W303-1A) exponential cultures in YPD treated with sodium selenite for the indicated times. Control samples were run from YPD-grown wild type cells that were shifted for 1 hour to YPGly (-Glu). (<b>B</b>) Growth assays of serial dilutions of wild type (W303-1A) cells in YPGal medium with the indicated concentrations of selenite. (<b>C</b>) As in (A) with samples from wild type and <i>Δreg1</i> (MML1442) cells. (<b>D</b>) Growth assays of serial culture dilutions of wild type (W303-1A), <i>Δsnf1</i> (Wsnf1) and <i>Δreg1</i> (MML1442) strains on YPD medium with selenite.</p

The Holocene stratified screes from Sierra de Albarracín (Iberian Ranges, Spain) and their paleoenvironmental significance

The most important stratified screes of the Iberian Range are found in Sierra de Albarracín. These slope deposits have been traditionally considered, without absolute datings, as having been formed during various Pleistocene cold phases. The aim of this paper is to establish the sedimentological, morphological, chronological, and paleoenvironmental characteristics of these deposits through the study of four profiles recorded in the Calomarde canyon (El Rollo, El Molino, and Royuela) and Toril. The most representative profile is that of El Rollo as it is formed by basal tufa and stratified scree layers separated by paleosoils. Radiocarbon datings obtained from paleosoil samples show that the sequence ranges between the early and middle Holocene. The profiles from El Molino and Royuela, as well as the upper levels of Toril, complete the sequence showing deposits from upper Holocene (Bronze Age and ‘Little Ice Age’). These data show the oscillations during the Holocene between colder phases, represented by the stratified screes, and warmer–wetter phases with soil development and local tufa deposits. This geomorphological and pedological response to the Holocene climatic variability shows its clearest records in the canyons. However, there are almost no Pleistocene accumulations – with the exception of that of Toril (minimum age of <43.5 ka BP). The possibility of relating this succession of Holocene environmental changes to known regional and global climatic stages converts these accumulations into the most important Holocene paleoenvironmental record from the Iberian Ranges and the most complete sequence of Holocene stratified screes from the Mediterranean area.Fil: Peña Monné, José Luis. Universidad de Zaragoza. Facultad de Filosofía y Letras; EspañaFil: Pérez Alberti, Augusto. Universidad de Santiago de Compostela; EspañaFil: Sampietro Vattuone, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Laboratorio de Geoarqueología; ArgentinaFil: Otero, Xose L.. Universidad de Santiago de Compostela; EspañaFil: Sánchez Fabre, Miguel. Universidad de Zaragoza. Facultad de Filosofía y Letras; EspañaFil: Longares Aladrén, Luis A.. Universidad de Zaragoza. Facultad de Filosofía y Letras; Españ