Efficacy and Tolerability of 6-Month Treatment with Tamsulosin Plus the Hexanic Extract of Serenoa repens versus Tamsulosin Plus 5-Alpha-Reductase Inhibitors for Moderate-to-Severe LUTS-BPH Patients: Results of a Paired Matched Clinical Study

The objective of this subset analysis was to evaluate and compare the efficacy and tolerability of two combination treatments for men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Data were from a real-world, open-label, prospective, and multicenter study performed in outpatient urology clinics. Men with moderate-to-severe LUTS/BPH received 6-month treatment with tamsulosin (TAM) in combination with either the hexanic extract of S. repens (HESr) or a 5-alpha-reductase inhibitor (5ARI). Changes in urinary symptoms and quality of life were measured using the IPSS and BII questionnaires, respectively. Treatment tolerability was assessed by recording adverse effects (AEs). Patients in the two study groups were matched using iterative and propensity score matching approaches. After iterative matching, data were available from 136 patients (n = 68 treated with TAM + 5ARI, n = 68 with TAM + HESr). After 6 months of treatment, mean (SD) IPSS total score improved by 7.7 (6.3) and 6.7 (5.0) points in the TAM + 5ARI and TAM + HESr groups, respectively (p = 0.272); mean BII total scores improved by 3.1 (2.9) and 2.9 (2.4) points (p = 0.751), respectively. AEs were reported by 26.5% and 10.3% of patients in the same groups, mostly affecting sexual function (p < 0.027). When used in a real-world setting to treat patients with moderate-severe LUTS/BPH, 6-month treatment with TAM + HESr was as effective as TAM + 5ARI, but with better tolerability. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Interacción entre clima y ocupación humana en la configuración del paisaje vegetal del Parque Nacional de Aigüestortes i Estany de Sant Maurici a lo largo de los últimos 15.000 años

The vegetation of the National Park of Aigüestortes i Estany de St Maurici is the result of an interaction between climate, plant community dynamics and the human occupation of the territory. The OCUPAproject aimed to reconstruct this interaction across the last millennia combining methods from palaeoecology and archaeology. The study focused primarily on the Sant Nicolau valley and built on the multidisciplinary analysis of the sedimentary archive of two lakes (Llebreta and Redó) and a number of archaeological sites located in shelters and outdoors. There is archaeological evidence of human presencesince 9000 yr cal BP, and a continuous record since 7500 yr cal BP. At early stages, humans transformed the surroundings of the shelters occupied and lithic tools indicate contacts with locations far away (i.e.,the Ebro plains). Since more than 3000 years ago, there has been human impact on the vegetation withoutinterruption until present. Initially, the impacts were mostly related to livestock: use of fire to open grazing lands, soil erosion and, during the medieval period, forestry and eutrophication of lakes. The agriculture impact in the lower part of the valley (e.g., Llebreta) occurred about 2100 yr ago, although some cereal grains and tools for harvesting have been found for the Neolithic. In the medieval period, the impact was higher than during the last centuries. In general, the changes in the human land use approximately follow the major changes in climate, but the specific causal link is likely related to the social and cultural dynamics of a broader territory since the Neolithic

Autophagy and Apoptosis Have a Role in the Survival or Death of Stallion Spermatozoa during Conservation in Refrigeration

Apoptosis has been recognized as a cause of sperm death during cryopreservation and a cause of infertility in humans, however there is no data on its role in sperm death during conservation in refrigeration; autophagy has not been described to date in mature sperm. We investigated the role of apoptosis and autophagy during cooled storage of stallion spermatozoa. Samples from seven stallions were split; half of the ejaculate was processed by single layer centrifugation, while the other half was extended unprocessed, and stored at 5°C for five days. During the time of storage, sperm motility (CASA, daily) and membrane integrity (flow cytometry, daily) were evaluated. Apoptosis was evaluated on days 1, 3 and 5 (active caspase 3, increase in membrane permeability, phosphatidylserine translocation and mitochondrial membrane potential) using flow cytometry. Furthermore, LC3B processing was investigated by western blotting at the beginning and at the end of the period of storage. The decrease in sperm quality over the period of storage was to a large extent due to apoptosis; single layer centrifugation selected non-apoptotic spermatozoa, but there were no differences in sperm motility between selected and unselected sperm. A high percentage of spermatozoa showed active caspase 3 upon ejaculation, and during the period of storage there was an increase of apoptotic spermatozoa but no changes in the percentage of live sperm, revealed by the SYBR-14/PI assay, were observed. LC3B was differentially processed in sperm after single layer centrifugation compared with native sperm. In processed sperm more LC3B-II was present than in non-processed samples; furthermore, in non-processed sperm there was an increase in LC3B-II after five days of cooled storage. These results indicate that apoptosis plays a major role in the sperm death during storage in refrigeration and that autophagy plays a role in the survival of spermatozoa representing a new pro-survival mechanism in spermatozoa not previously described

Classification, prevalence, and outcomes of anticancer therapy-induced cardiotoxicity: the CARDIOTOX registry

AIM: Cardiotoxicity (CTox) is a major side effect of cancer therapies, but uniform diagnostic criteria to guide clinical and research practices are lacking. METHODS AND RESULTS: We prospectively studied 865 patients, aged 54.7 ± 13.9; 16.3% men, scheduled for anticancer therapy related with moderate/high CTox risk. Four groups of progressive myocardial damage/dysfunction were considered according to current guidelines: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥50%; moderate, LVD with LVEF 40-49%; and severe, LVD with LVEF ≤40% or symptomatic heart failure. Cardiotoxicity was defined as new or worsening of myocardial damage/ventricular function from baseline during follow-up. Patients were followed for a median of 24 months. Cardiotoxicity was identified in 37.5% patients during follow-up [95% confidence interval (CI) 34.22-40.8%], 31.6% with mild, 2.8% moderate, and 3.1% with severe myocardial damage/dysfunction. The mortality rate in the severe CTox group was 22.9 deaths per 100 patients-year vs. 2.3 deaths per 100 patients-year in the rest of groups, hazard ratio of 10.2 (95% CI 5.5-19.2) (P < 0.001). CONCLUSIONS: The majority of patients present objective data of myocardial injury/dysfunction during or after cancer therapy. Nevertheless, severe CTox, with a strong prognostic relationship, was comparatively rare. This should be reflected in protocols for clinical and research practices

Modulation of plant HMG-CoA reductase by protein phosphatase 2A: Positive and negative control at a key node of metabolism

The enzyme HMG-CoA reductase (HMGR) has a key regulatory role in the mevalonate pathway for isoprenoid biosynthesis, critical not only for normal plant development, but also for the adaptation to demanding environmental conditions. Consistent with this notion, plant HMGR is modulated by many diverse endogenous signals and external stimuli. Protein phosphatase 2A (PP2A) is involved in auxin, abscisic acid, ethylene and brassinosteroid signaling and now emerges as a positive and negative multilevel regulator of plant HMGR, both during normal growth and in response to a variety of stress conditions. The interaction with HMGR is mediated by B" regulatory subunits of PP2A, which are also calcium binding proteins. The new discoveries uncover the potential of PP2A to integrate developmental and calcium-mediated environmental signals in the control of plant HMGR

Na+ controls hypoxic signalling by the mitochondrial respiratory chain

All metazoans depend on O2 delivery and consumption by the mitochondrial oxidative phosphorylation (OXPHOS) system to produce energy. A decrease in O2 availability (hypoxia) leads to profound metabolic rewiring. In addition, OXPHOS uses O2 to produce reactive oxygen species (ROS) that can drive cell adaptations through redox signalling, but also trigger cell damage1–4, and both phenomena occur in hypoxia4–8. However, the precise mechanism by which acute hypoxia triggers mitochondrial ROS production is still unknown. Ca2+ is one of the best known examples of an ion acting as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential and collaborating in ion transport10. Here we show that Na+ acts as a second messenger regulating OXPHOS function and ROS production by modulating fluidity of the inner mitochondrial membrane (IMM). We found that a conformational shift in mitochondrial complex I during acute hypoxia11 drives the acidification of the matrix and solubilization of calcium phosphate precipitates. The concomitant increase in matrix free-Ca2+ activates the mitochondrial Na+/Ca2+ exchanger (NCLX), which imports Na+ into the matrix. Na+ interacts with phospholipids reducing IMM fluidity and mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III, generating a redox signal. Inhibition of mitochondrial Na+ import through NCLX is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ import into the mitochondrial matrix controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences in cellular metabolism

Sheep herd management during the Early Neolithic in the inland of the Iberian Peninsula. Isotopic analyses of El Mirador cave (Sierra de Atapuerca, Spain)

The beginning of husbandry in the Iberian Peninsula has been documented from the second half of the 6th millennium BCE and was based on the breeding of domestic caprines, mainly sheep. The first evidence of these practices comes from the Mediterranean region, but they quickly expanded inland. Previous studies have reported on the importance of the El Mirador sheepfold cave (Sierra de Atapuerca, Burgos, Spain) for understanding the process of the adoption of a farming economy in this inland region. In this study, we focus on husbandry and sheep management occurring in the 6th and 5th millennium cal BCE occupations of El Mirador cave by means of sequential oxygen (δ18O) and carbon (δ13C) isotope analyses in sheep molar tooth enamel. The results show a rapid adaptation and adoption of domestic sheep in the inland of the Iberian Peninsula. In El Mirador cave, well-organised sheep breeding was developed based on the concentration of births at the end of winter and early spring, for a period of ~2.64 months, which made husbandry more compatible with other economic activities. In 5th millennium levels, autumn births were also documented and may be indicative of the intervention of the shepherd in the reproductive cycle of the sheep and of a progressive adaptation of these animals to the interior of the Peninsula. All these strategies may have been supported by the recurrent occupations of the sheepfold, flocks grazing in the areas surrounding the cave and the possible use of leaf fodder in winter

Quality of life in patients with food allergy

Food allergy has increased in developed countries and can have a dramatic effect on quality of life, so as to provoke fatal reactions. We aimed to outline the socioeconomic impact that food allergy exerts in this kind of patients by performing a complete review of the literature and also describing the factors that may influence, to a greater extent, the quality of life of patients with food allergy and analyzing the different questionnaires available. Hitherto, strict avoidance of the culprit food(s) and use of emergency medications are the pillars to manage this condition. Promising approaches such as specific oral or epicutaneous immunotherapy and the use of monoclonal antibodies are progressively being investigated worldwide. However, even that an increasing number of centers fulfill those approaches, they are not fully implemented enough in clinical practice. The mean annual cost of health care has been estimated in international dollars (I$) 2016 for food-allergic adults and I$1089 for controls, a difference of I$927 (95$324–I$1530). A similar result was found for adults in each country, and for children, and interestingly, it was not sensitive to baseline demographic differences. Cost was significantly related to severity of illness in cases in nine countries. The constant threat of exposure, need for vigilance and expectation of outcome can have a tremendous impact on quality of life. Several studies have analyzed the impact of food allergy on health-related quality of life (HRQL) in adults and children in different countries. There have been described different factors that could modify HRQL in food allergic patients, the most important of them are perceived disease severity, age of the patient, peanut or soy allergy, country of origin and having allergy to two or more foods. Over the last few years, several different specific Quality of Life questionnaires for food allergic patients have been developed and translated to different languages and cultures. It is important to perform lingual and cultural translations of existent questionnaires in order to ensure its suitability in a specific region or country with its own socioeconomic reality and culture. Tools aimed at assessing the impact of food allergy on HRQL should be always part of the diagnostic work up, in order to provide a complete basal assessment, to highlight target of intervention as well as to evaluate the effectiveness of interventions designed to cure food allergy. HRQL may be the only meaningful outcome measure available for food allergy measuring this continuous burden