17 research outputs found
Ancient Bacterial Genomes Reveal a High Diversity of Treponema pallidum Strains in Early Modern Europe
Syphilis is a globally re-emerging disease, which has marked European history with a devastating epidemic at the end of the 15th century. Together with non-venereal treponemal diseases, like bejel and yaws, which are found today in subtropical and tropical regions, it currently poses a substantial health threat worldwide. The origins and spread of treponemal diseases remain unresolved, including syphilis' potential introduction into Europe from the Americas. Here, we present the first genetic data from archaeological human remains reflecting a high diversity of Treponema pallidumin early modern Europe. Our study demonstrates that a variety of strains related to both venereal syphilis and yaws-causing T. pallidum subspecies were already present in Northern Europe in the early modern period. We also discovered a previously unknown T. pallidum lineage recovered as a sister group to yaws- and bejel-causing lineages. These findings imply a more complex pattern of geographical distribution and etiology of early treponemal epidemics than previously understood.Peer reviewe
Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment
Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death
Autonomous cortisol secretion in patients with primary aldosteronism: prevalence and implications on cardiometabolic profile and on surgical outcomes
Purpose: The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes.
Methods: This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 ÎŒg/dL (confirmed ACS if >5 ÎŒg/dL and possible ACS if 1.8â5 ÎŒg/dL) in the absence of spe cific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels.
Results: The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACSâPA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACSâPA and PA-only patients was simil ar, except for older age and larger tumor size of the adrenal lesion in the ACSâPA group. When comparing the ACSâPA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64â22.32)) and cardiovascular events (OR 5.0 (2.29â11.07)) was higher in ACSâPA patients than in ACS patients. The coexistence of ACS in patien ts with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACSâPA and PA-only groups.
Conclusion: Co-secretion of cortisol and aldosterone affects almost one-thi rd of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACSâPA and PA-only are similar
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality
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Dietary αâLinolenic Acid, Marine Ïâ3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvenciĂłn con DIeta MEDiterrĂĄnea (PREDIMED) Study
Background: Epidemiological evidence suggests a cardioprotective role of αâlinolenic acid (ALA), a plantâderived Ïâ3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine Ïâ3 fatty acids (longâchain nâ3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to allâcause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for longâchain nâ3 polyunsaturated fatty acids (â„500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvenciĂłn con DIeta MEDiterrĂĄnea (PREDIMED) trial. Multivariableâadjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9ây followâup, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56â0.92) for allâcause mortality and 0.95 (95% CI 0.58â1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for longâchain nâ3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67â1.05) for allâcause mortality, 0.61 (95% CI 0.39â0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29â0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22â1.01) for sudden cardiac death. The highest reduction in allâcause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45â0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to allâcause mortality, whereas protection from cardiac mortality is limited to fishâderived longâchain nâ3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639
Testing virtual reality-based cue-exposure software: Which cue-elicited responses best discriminate between patients with eating disorders and healthy controls?
Purpose: Virtual reality (VR) technologies have been proposed as a new tool able to improve on in vivo exposure in patients with eating disorders. This study assessed the validity of a VR-based software for cue exposure therapy (CET) in people with bulimia nervosa (BN) and binge eating disorder (BED). Methods: Fifty eight outpatients (33 BN and 25 BED) and 135 healthy participants were exposed to 10 craved virtual foods and a neutral cue in four experimental virtual environments (kitchen, dining room, bedroom, and cafeteria). After exposure to each VR scenario, food craving and anxiety were assessed. The frequency/severity of episodes of uncontrollable overeating was also assessed and body mass index was measured prior to the exposure. Results: In both groups, craving and anxiety responses when exposed to the food-related virtual environments were significantly higher than in the neutral-cue virtual environment. However, craving and anxiety levels were higher in the clinical group. Furthermore, cue-elicited anxiety was better at discriminating between clinical and healthy groups than cue-elicited craving. Conclusions: This study provides evidence of the ability of food-related VR environments to provoke food craving and anxiety responses in BN and BED patients and highlights the need to consider both responses during treatment. The results support the use of VR-CET in the treatment of eating disorder patients characterized by binge-eating and people with high bulimic symptoms
Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment
Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death.status: publishe
Datos oceanogrĂĄficos baÌsicos de las campanÌas âFRONTS- 1992â (octubre-noviembre 1992) y âVariabilidad de mesoescala en el MediterrĂĄneo occidental" (junio 1993)
Datos oceanogrĂĄficos baÌsicos de las campanÌas âFRONTS- 1992â (octubre-noviembre 1992) y âVariabilidad de mesoescala en el MediterrĂĄneo occidental" (junio 1993): 3-117 (1995).-- MasĂł, Mercedes ... et. al.-- 115 pagesLa campaña FRONTS 92 se desarrollĂł entre los dĂas 15 de Octubre y 4 de Noviemhre de 1992, a bordo del B/O "GarcĂa del Cid". Tuvo como objetivos el estudio de las relaciones entre la variabilidad temporal de factores fĂsicos y fenĂłmenos biolĂłgicos. Esta campaña formaba parte del proyecto de investigaciĂłn "Acoplamiento entre entre la variabilidad temporal de factores fĂsicos y fenĂłmenos biolĂłgicos en el MediterrĂĄneo Noroccidental", subvencionado por CYCIT.
La campaña oceanogrĂĄfica ''Variabilidad de Mesoescala en el MediterrĂĄneo Occidental (VARIMED)" tuvo lugar entre los dĂas 1 y 29 de Junio a bordo del BIO "Hesperides". Tuvo como objetivos el estudio del papel de las estructuras de mesoescala en la circulaciĂłn general de la capa superficial y en los procesos que determinan tanto la productividad biolĂłgica como el transporte de organismos y material sedimentarioEsta campaña formaba parte del proyecto de investigaciĂłn "Acoplamiento entre la variabilidad temporal de factores fĂsicos y fenĂłmenos biolĂłgicos en el MediterrĂĄneo Noroccidental", subvencionado por CYCITPeer Reviewe