Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice.

Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions.pre-print5,92 M

Calibration of Gamma Ray Impacts in Monolithic-Based Detectors Using Voronoi Diagrams

[EN] Molecular imaging systems, such as positron emission tomography (PET), use detectors providing energy and a 3-D interaction position of a gamma ray within a scintillation block. Monolithic crystals are becoming an alternative to crystal arrays in PET. However, calibration processes are required to correct for nonuniformities, mainly produced by the truncation of the scintillation light distribution at the edges. We propose a calibration method based on the Voronoi diagrams. We have used $50 \times 50 \times 15$ mm(3) LYSO blocks coupled to a $12\times 12$ SiPMs array. We have first studied two different interpolation algorithms: 1) weighted average method (WAM) and 2) natural neighbor (NN). We have compared them with an existing calibration based on 1-D monomials. Here, the crystal was laterally black painted and a retroreflector (RR) layer added to the entrance face. The NN exhibited the best results in terms of XY impact position, depth of Interaction, and energy, allowing us to calibrate the whole scintillation volume. Later, the NN interpolation has been tested against different crystal surface treatments, allowing always to correct edge effects. Best energy resolutions were observed when using the reflective layers (12%-14%). However, better linearity was observed with the treatments using black paint. In particular, we obtained the best overall performance when lateral black paint is combined with the RR.This work was supported in part by the European Research Council through the European Union's Horizon 2020 Research and Innovation Program under Grant 695536, and in part by the Spanish Ministerio de Economia, Industria y Competitividad under Grant TEC2016-79884-C2-1-R.Freire, M.; Gonzalez-Montoro, A.; Sánchez Martínez, F.; Benlloch Baviera, JM.; González Martínez, AJ. (2020). Calibration of Gamma Ray Impacts in Monolithic-Based Detectors Using Voronoi Diagrams. IEEE Transactions on Radiation and Plasma Medical Sciences. 4(3):350-360. https://doi.org/10.1109/TRPMS.2019.2947716S3503604

Characterization of a High-Aspect Ratio Detector With Lateral Sides Readout for Compton PET

This work was supported by the European Research Council through the European Union's Horizon 2020 Research and Innovation Program under Grant 695536.Barrio, J.; Cucarella, N.; González Martínez, AJ.; Freire, M.; Ilisie, V.; Benlloch Baviera, JM. (2020). Characterization of a High-Aspect Ratio Detector With Lateral Sides Readout for Compton PET. IEEE Transactions on Radiation and Plasma Medical Sciences. 4(5):546-554. https://doi.org/10.1109/TRPMS.2020.3006862S5465544

Use of colorants in pottery fragments coverings from the Río Salado (Buenos Aires province, Argentina)

En la microrregión del río Salado bonaerense numerosos fragmentos de alfarería muestran el uso de coberturas minerales colorantes, mayoritariamente rojas y, en baja proporción, blanquecinas. Con estas sustancias los cazadores-recolectores-pescadores efectuaron coberturas o decoraciones pintadas en las superficies de diversos contenedores. En este trabajo nos proponemos identificar y analizar los datos composicionales de la fracción inorgánica de las coberturas de estos dos colores que fueron aplicadas en las cerámicas de los diferentes sitios bajo estudio. Las técnicas analíticas utilizadas fueron fluorescencia de rayos X dispersiva en longitud de onda (FRXWD), fluorescencia de rayos X con geometría de reflexión Total (FRXT), difracción de rayos X (DRX) y espectrometría Raman. Los resultados, que consideramos preliminares, señalan que los recipientes con coberturas rojas, mayoritarios en las colecciones, muestran el uso de la hematita. La cobertura blanquecina de los recipientes fue resultado de mezclas que contienen calcio y titanio. El yeso o el hueso, que aparecen también en algunas de las muestras, indicarían que pudieron ser utilizados como minerales colorantes o como ligantes en la preparación de las coberturas de los recipientes.Numerous pottery fragments from the río Salado microregion (Buenos Aires province) show the use of mineral colorants coverings, mainly red and occasionally white. With these colorants the hunter gatherer fishers groups made coverings or painted decorations on the surfaces of several pots. The aim of this paper is to identify and analyze the compositional data from the inorganic fraction of coverings of these two colors which were applied to pots from different archaeological sites. The analytical techniques used were dispersive X ray fluorescence in length of wave (FRXWD), X-ray fluorescence with geometry of Total reflection (FRXT), X ray diffraction (XRD) and Raman spectrometry. Preliminary results show that pots with red topping, the most frequent in the assemblages, are composed by hematite. White coverings are the result of mixtures that contain calcium and titanium. Gypsum and bone, which are present in some of the samples, could have been used as mineral colorants or as binders for the toppings preparation.Facultad de Ciencias Naturales y Muse

Rationale, design and preliminary results of the GALIPEMIAS study (prevalence and lipid control of familial dyslipidemia in Galicia, northwest Spain)

[Abstract] Aims. There is little information on the familial nature of dyslipidemias in the Spanish population. This knowledge could have potential diagnostic and treatment implications. The objective of the GALIPEMIAS study was to determine the prevalence of familial dyslipidemia in Galicia, as well as determine the degree of lipid control in the participants. Prevalence of atherosclerotic cardiovascular disease (ASCVD) was also estimated. This paper presents the design, methodology and selected preliminary results. Methodology. A cross‐sectional study was performed in the population aged ≥18 years using cluster sampling and then random sampling. A sample of 1000 subjects was calculated and divided into three sequential phases with a specific methodology for each one. Phase I: selection of subjects from the general population and collection of informed consent documents; Phase II: collection of data from the digital clinical history to select subjects with dyslipidemia according to study criteria; Phase III: personal interview, blood analysis, family tree, and definitive diagnosis of dyslipidemia. Prevalence of different diseases and active medication was analysed. Corrected prevalence (to the reference population) of different risk factors and ASCVD was estimated. Results. Phase I participation was 89.5%. We extracted complete information from 93% of the participants (Phase II). According to the study′s own criteria, 56.5% (n = 527) of the participants had some form of dyslipidemia and almost 33.7% of them had familial dyslipidemia with autosomal dominant inherit pattern. The corrected prevalence of ASCVD was 5.1% (95% CI 3.1‐7.2). Conclusions. Dyslipidemia was the most prevalent cardiovascular risk factor in our population with an autosomal dominant inheritance pattern in one out of every three dyslipidemia cases. Approximately, 5.1% of the sample population aged ≥18 has suffered an episode of ACVD

GDF15 and ACE2 stratify COVID-19 patients according to severity while ACE2 mutations increase infection susceptibility

Coronavirus disease 19 (COVID-19) is a persistent global pandemic with a very heterogeneous disease presentation ranging from a mild disease to dismal prognosis. Early detection of sensitivity and severity of COVID-19 is essential for the development of new treatments. In the present study, we measured the levels of circulating growth differentiation factor 15 (GDF15) and angiotensin-converting enzyme 2 (ACE2) in plasma of severity-stratified COVID-19 patients and uninfected control patients and characterized the in vitro effects and cohort frequency of ACE2 SNPs. Our results show that while circulating GDF15 and ACE2 stratify COVID-19 patients according to disease severity, ACE2 missense SNPs constitute a risk factor linked to infection susceptibility

Effectiveness of a cognitive behavioral intervention in patients with medically unexplained symptoms: cluster randomized trial

BACKGROUND: Medically unexplained symptoms are an important mental health problem in primary care and generate a high cost in health services.Cognitive behavioral therapy and psychodynamic therapy have proven effective in these patients. However, there are few studies on the effectiveness of psychosocial interventions by primary health care. The project aims to determine whether a cognitive-behavioral group intervention in patients with medically unexplained symptoms, is more effective than routine clinical practice to improve the quality of life measured by the SF-12 questionary at 12 month. METHODS/DESIGN: This study involves a community based cluster randomized trial in primary healthcare centres in Madrid (Spain). The number of patients required is 242 (121 in each arm), all between 18 and 65 of age with medically unexplained symptoms that had seeked medical attention in primary care at least 10 times during the previous year. The main outcome variable is the quality of life measured by the SF-12 questionnaire on Mental Healthcare. Secondary outcome variables include number of consultations, number of drug (prescriptions) and number of days of sick leave together with other prognosis and descriptive variables. Main effectiveness will be analyzed by comparing the percentage of patients that improve at least 4 points on the SF-12 questionnaire between intervention and control groups at 12 months. All statistical tests will be performed with intention to treat. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. DISCUSSION: This study aims to provide more insight to address medically unexplained symptoms, highly prevalent in primary care, from a quantitative methodology. It involves intervention group conducted by previously trained nursing staff to diminish the progression to the chronicity of the symptoms, improve quality of life, and reduce frequency of medical consultations. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, number NCT01484223 [http://ClinicalTrials.gov].S

Differences in clinical features and mortality in very old unvaccinated patients (≥ 80 years) hospitalized with COVID-19 during the first and successive waves from the multicenter SEMI-COVID-19 Registry (Spain)

Background: Old age is one of the most important risk factors for severe COVID-19. Few studies have analyzed changes in the clinical characteristics and prognosis of COVID-19 among older adults before the availability of vaccines. This work analyzes differences in clinical features and mortality in unvaccinated very old adults during the first and successive COVID-19 waves in Spain. Methods This nationwide, multicenter, retrospective cohort study analyzes unvaccinated patients >= 80 years hospitalized for COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry). Patients were classified according to whether they were admitted in the first wave (March 1-June 30, 2020) or successive waves (July 1-December 31, 2020). The endpoint was all-cause in-hospital mortality, expressed as the case fatality rate (CFR). Results Of the 21,461 patients hospitalized with COVID-19, 5,953 (27.7%) were >= 80 years (mean age [IQR]: 85.6 [82.3-89.2] years). Of them, 4,545 (76.3%) were admitted during the first wave and 1,408 (23.7%) during successive waves. Patients hospitalized in successive waves were older, had a greater Charlson Comorbidity Index and dependency, less cough and fever, and met fewer severity criteria at admission (qSOFA index, PO2/FiO2 ratio, inflammatory parameters). Significant differences were observed in treatments used in the first (greater use of antimalarials, lopinavir, and macrolides) and successive waves (greater use of corticosteroids, tocilizumab and remdesivir). In-hospital complications, especially acute respiratory distress syndrome and pneumonia, were less frequent in patients hospitalized in successive waves, except for heart failure. The CFR was significantly higher in the first wave (44.1% vs. 33.3%; -10.8%; p = 95 years (54.4% vs. 38.5%; -15.9%; p < 0.001). After adjustments to the model, the probability of death was 33% lower in successive waves (OR: 0.67; 95% CI: 0.57-0.79). Conclusions Mortality declined significantly between the first and successive waves in very old unvaccinated patients hospitalized with COVID-19 in Spain. This decline could be explained by a greater availability of hospital resources and more effective treatments as the pandemic progressed, although other factors such as changes in SARS-CoV-2 virulence cannot be ruled out

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 +/- 20.6% vs 93.6 +/- 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 +/- 5.2 mm vs 19.9 +/- 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO