Aging is associated with an earlier arrival of reflected waves without a distal shift in reflection sites

Background-Despite pronounced increases in central pulse wave velocity (PWV) with aging, reflected wave transit time (RWTT), traditionally defined as the timing of the inflection point (T-INF) in the central pressure waveform, does not appreciably decrease, leading to the controversial proposition of a "distal-shift" of reflection sites. T-INF, however, is exceptionally prone to measurement error and is also affected by ejection pattern and not only by wave reflection. We assessed whether RWTT, assessed by advanced pressure-flow analysis, demonstrates the expected decline with aging. Methods and Results-We studied a sample of unselected adults without cardiovascular disease (n=48; median age 48 years) and a clinical population of older adults with suspected/established cardiovascular disease (n=164; 61 years). We measured central pressure and flow with carotid tonometry and phase-contrast MRI, respectively. We assessed RWTT using wave-separation analysis (RWTTWSA) and partially distributed tube-load (TL) modeling (RWTTTL). Consistent with previous reports, T-INF did not appreciably decrease with age despite pronounced increases in PWV in both populations. However, aging was associated with pronounced decreases in RWTTWSA (general population -15.0 ms/decade, P<0.001; clinical population -9.07 ms/decade, P=0.003) and RWTTTL (general -15.8 ms/decade, P<0.001; clinical -11.8 ms/decade, P<0.001). There was no evidence of an increased effective reflecting distance by either method. TINF was shown to reliably represent RWTT only under highly unrealistic assumptions about input impedance. Conclusions-RWTT declines with age in parallel with increased PWV, with earlier effects of wave reflections and without a distal shift in reflecting sites. These findings have important implications for our understanding of the role of wave reflections with aging

The Large Aperture GRB Observatory

The Large Aperture GRB Observatory (LAGO) is aiming at the detection of the high energy (around 100 GeV) component of Gamma Ray Bursts, using the single particle technique in arrays of Water Cherenkov Detectors (WCD) in high mountain sites (Chacaltaya, Bolivia, 5300 m a.s.l., Pico Espejo, Venezuela, 4750 m a.s.l., Sierra Negra, Mexico, 4650 m a.s.l). WCD at high altitude offer a unique possibility of detecting low gamma fluxes in the 10 GeV - 1 TeV range. The status of the Observatory and data collected from 2007 to date will be presented.Comment: 4 pages, proceeding of 31st ICRC 200

Water Cherenkov Detectors response to a Gamma Ray Burst in the Large Aperture GRB Observatory

In order to characterise the behaviour of Water Cherenkov Detectors (WCD) under a sudden increase of 1 GeV - 1 TeV background photons from a Gamma Ray Burst (GRB), simulations were conducted and compared to data acquired by the WCD of the Large Aperture GRB Observatory (LAGO). The LAGO operates arrays of WCD at high altitude to detect GRBs using the single particle technique. The LAGO sensitivity to GRBs is derived from the reported simulations of the gamma initiated particle showers in the atmosphere and the WCD response to secondaries.Comment: 5 pages, proceeding of the 31st ICRC 200

American College of Cardiology/American Heart Association (ACC/AHA) Class I Guidelines for the Treatment of Cholesterol to Reduce Atherosclerotic Cardiovascular Risk: Implications for US Hispanics/Latinos Based on Findings From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

BACKGROUND: The prevalence estimates of statin eligibility among Hispanic/Latinos living in the United States under the new 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol treatment guidelines are not known. METHODS AND RESULTS: We estimated prevalence of statin eligibility under 2013 ACC/AHA and 3rd National Cholesterol Education Program Adult Treatment Panel (NCEP/ATP III) guidelines among Hispanic Community Health Study/Study of Latinos (n=16 415; mean age 41 years, 40% males) by using sampling weights calibrated to the 2010 US census. We examined the characteristics of Hispanic/Latinos treated and not treated with statins under both guidelines. We also redetermined the statin-therapy eligibility by using black risk estimates for Dominicans, Cubans, Puerto Ricans, and Central Americans. Compared with NCEP/ATP III guidelines, statin eligibility increased from 15.9% (95% CI 15.0-16.7%) to 26.9% (95% CI 25.7-28.0%) under the 2013 ACC/AHA guidelines. This was mainly driven by the ≥7.5% atherosclerotic cardiovascular disease risk criteria (prevalence 13.9% [95% CI 13.0-14.7%]). Of the participants eligible for statin eligibility under NCEP/ATP III and ACC/AHA guidelines, only 28.2% (95% CI 26.3-30.0%) and 20.6% (95% CI 19.4-21.9%) were taking statins, respectively. Statin-eligible participants who were not taking statins had a higher prevalence of cardiovascular risk factors compared with statin-eligible participants who were taking statins. There was no significant increase in statin eligibility when atherosclerotic cardiovascular disease risk was calculated by using black estimates instead of recommended white estimates (increase by 1.4%, P=0.12) for Hispanic/Latinos. CONCLUSIONS: The eligibility of statin therapy increased consistently across all Hispanic/Latinos subgroups under the 2013 ACC/AHA guidelines and therefore will potentially increase the number of undertreated Hispanic/Latinos in the United States

A Catalog of the Highest-energy Cosmic Rays Recorded during Phase I of Operation of the Pierre Auger Observatory

A catalog containing details of the highest-energy cosmic rays recorded through the detection of extensive air showers at the Pierre Auger Observatory is presented with the aim of opening the data to detailed examination. Descriptions of the 100 showers created by the highest-energy particles recorded between 2004 January 1 and 2020 December 31 are given for cosmic rays that have energies in the range 78-166 EeV. Details are also given on a further nine very energetic events that have been used in the calibration procedure adopted to determine the energy of each primary. A sky plot of the arrival directions of the most energetic particles is shown. No interpretations of the data are offered

Human fertilization: epididymal hCRISP1 mediates sperm zona pellucida binding through its interaction with ZP3

Human epididymal CRISP1 (hCRISP1) associates with sperm during maturation and participates in gamete fusion through egg complementary sites. Its homology with both rodent epididymal CRISP1 and CRISP4 reported to participate in the previous stage of sperm binding to the zona pellucida (ZP), led us to further investigate the functional role of hCRISP1 by studying its involvement in human sperm-ZP interaction. Human hemizona (HZ) were inseminated with human capacitated sperm in the presence of either anti-hCRISP1 polyclonal antibody to inhibit sperm hCRISP1, or bacterially-expressed hCRISP1 (rec-hCRISP1) to block putative hCRISP1 binding sites in the ZP. Results revealed that both anti-hCRISP1 and rec-hCRISP1 produced a significant inhibition in the number of sperm bound per HZ compared with the corresponding controls. The finding that neither anti-hCRISP1 nor rec-hCRISP1 affected capacitation-associated events (i.e. sperm motility, protein tyrosine phosphorylation or acrosome reaction) supports a specific inhibition at the sperm?egg interaction level. Moreover, immunofluorescence experiments using human ZP-intact eggs revealed the presence of complementary sites for hCRISP1 in the ZP. To identify the ligand of hCRISP1 in the ZP, human recombinant proteins ZP2, ZP3 and ZP4 expressed in insect cells were co-incubated with hCRISP1 and protein?protein interaction was analyzed by ELISA. Results revealed that rec-hCRISP1 mainly interacted with ZP3 in a dose-dependent and saturable manner, supporting the specificity of this interaction. Altogether, these results indicate that hCRISP1 is a multifunctional protein involved notonly in sperm?egg fusion but also in the previous stage of sperm?ZP binding through its specific interaction with human ZP3.Fil: Maldera, Julieta Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Heidelberg University. Center for Molecular Biology; AlemaniaFil: Weigel Muñoz, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Chirinos, M.. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran; MéxicoFil: Busso, Dolores. Pontificia Universidad Católica de Chile; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Raffo, F. G. E.. Centro Médico Fertilab; ArgentinaFil: Battistone, Maria Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Blaquier, J. A.. Centro Médico Fertilab; ArgentinaFil: Larrea, F.. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran; MéxicoFil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentin

Risk score for first-screening of prevalent undiagnosed chronic kidney disease in Peru: the CRONICAS-CKD risk score.

BACKGROUND: Chronic Kidney Disease (CKD) represents a great burden for the patient and the health system, particularly if diagnosed at late stages. Consequently, tools to identify patients at high risk of having CKD are needed, particularly in limited-resources settings where laboratory facilities are scarce. This study aimed to develop a risk score for prevalent undiagnosed CKD using data from four settings in Peru: a complete risk score including all associated risk factors and another excluding laboratory-based variables. METHODS: Cross-sectional study. We used two population-based studies: one for developing and internal validation (CRONICAS), and another (PREVENCION) for external validation. Risk factors included clinical- and laboratory-based variables, among others: sex, age, hypertension and obesity; and lipid profile, anemia and glucose metabolism. The outcome was undiagnosed CKD: eGFR < 60 ml/min/1.73m2. We tested the performance of the risk scores using the area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive/negative predictive values and positive/negative likelihood ratios. RESULTS: Participants in both studies averaged 57.7 years old, and over 50% were females. Age, hypertension and anemia were strongly associated with undiagnosed CKD. In the external validation, at a cut-off point of 2, the complete and laboratory-free risk scores performed similarly well with a ROC area of 76.2% and 76.0%, respectively (P = 0.784). The best assessment parameter of these risk scores was their negative predictive value: 99.1% and 99.0% for the complete and laboratory-free, respectively. CONCLUSIONS: The developed risk scores showed a moderate performance as a screening test. People with a score of ≥ 2 points should undergo further testing to rule out CKD. Using the laboratory-free risk score is a practical approach in developing countries where laboratories are not readily available and undiagnosed CKD has significant morbidity and mortality

TRPM8, a Versatile Channel in Human Sperm

BACKGROUND:The transient receptor potential channel (TRP) family includes more than 30 proteins; they participate in various Ca(2+) dependent processes. TRPs are functionally diverse involving thermal, chemical and mechanical transducers which modulate the concentration of intracellular Ca(2+) ([Ca(2+)]i). Ca(2+) triggers and/or regulates principal sperm functions during fertilization such as motility, capacitation and the acrosome reaction. Nevertheless, the presence of the TRPM subfamily in sperm has not been explored. PRINCIPAL FINDINGS:Here we document with RT-PCR, western blot and immunocitochemistry analysis the presence of TRPM8 in human sperm. We also examined the participation of this channel in sperm function using specific agonists (menthol and temperature) and antagonists (BCTC and capsazepine). Computer-aided sperm analysis revealed that menthol did not significantly alter human sperm motility. In contrast, menthol induced the acrosome reaction in human sperm. This induction was inhibited about 70% by capsazepine (20 microM) and 80% by BCTC (1.6 microM). Activation of TRPM8 either by temperature or menthol induced [Ca(2+)]i increases in human sperm measured by fluorescence in populations or individual sperm cells, effect that was also inhibited by capsazepine (20 microM) and BCTC (1.6 microM). However, the progesterone and ZP3-induced acrosome reaction was not inhibited by capsazepine or BCTC, suggesting that TRPM8 activation triggers this process by a different signaling pathway. CONCLUSIONS:This is the first report dealing with the presence of a thermo sensitive channel (TRPM8) in human sperm. This channel could be involved in cell signaling events such as thermotaxis or chemotaxis