Evidence of cyclic climatic changes recorded in clay mineral assemblages from a continental Paleocene-Eocene sequence, northwestern Argentina

The continental Paleocene-Eocene sequence investigated in this study belongs to the Salta Group, deposited in an intracontinental rift, the Salta Basin (NW Argentina), that evolved from the lower Cretaceous to the middle Paleogene, and is subdivided into the Pirgua, the Balbuena and the Santa Barbara Subgroups. The Maíz Gordo Formation (200 m thick) is the middle unit of the Santa Bárbara Subgroup, deposited during late post-rift sedimentation. We studied the mineralogy of fine-grained horizons of this formation by X-ray diffraction and Scanning Electron Microscopy (SEM) in order to examine the connection between vertical changes in clay mineralogy in alluvial sediments and paleosols, and global paleoclimatic changes registered during the Paleogene. Paleosols vary from calcic vertisols in the lowermost levels, to inseptisols and gleysols in intermediate positions, to gleyed oxisols in the upper section, indicating increased chemical weathering through time. Clay mineral relative abundances vary with a general increase in kaolinite content from bottom to top. However, at one site there are significant variations in kaolinite/muscovite (Kln/Ms) that define five cycles of kaolinite abundance and Kln/Ms. that indicate cyclic patterns of paleoprecipitation and paleotemperature. These are interpreted as several short-lived hyperthermals during the Paleocene-early Eocene in the Southern Hemisphere, which correlate with well-established episodes of warmth documented from the Northern Hemisphere

Duodenal metastasis of alveolar soft part sarcoma

Aveolar soft part sarcoma is a rare tumor responsible for about 1% of all soft tissue sarcomas, affecting mostly adolescents and young adults. ASPS has curious patterns of metastatic spread, with seldom lymph node involvement. Lung, bone and brain are the most common metastatic places. Small bowel metastasis are infrequent, having found reported only one case of duodenal metastasis with polypous appearance. We describe a case of duodenal metastasis presenting as abdominal mass five years after initial diagnosis of alveolar soft part sarcoma

Cicloestratigrafía del Grupo Enciso, Cuenca oriental de Cameros (N de España)

El Grupo Enciso (Cretácico Inferior) se localiza en la parte oriental de la Cuenca de Cameros. Está formado por arenis- cas, limolitas, margas y calizas organizadas en ciclos de diferente rango que han sido interpretados como de origen orbital (Angulo y Muñoz, 2013; Hernán, 2018; Muñoz et al., en prensa). En los alrededores de Navalsaz (La Rioja) se ha levantado un perfil estratigráfico de 1.371 m donde se han medido valores de susceptibilidad magnética cada 50 cm y se han tomado muestras cada metro para la medida en laboratorio del contenido en carbonato y de parámetros de color (CIE L*a*b*). Se han construido series de tiempo continuas cuantitativas de la susceptibilidad magnética, el contenido total de carbonato, la luminosidad (L*), y las coordenadas rojo/verde (a*) y amarillo/azul (b*). El análisis espectral de estas series de tiempo ha puesto de manifiesto la existencia de ciclos referibles a las frecuencias de Milankovitch de excentricidad, oblicuidad y precesión. The Enciso Group (Lower Cretaceous) is located in the eastern part of Cameros Basin. It is made up of sandstones, limolites, marls and limestones organized in different rank cycles which have been interpreted as orbitally-controlled cycles (Angulo and Muñoz, 2013; Hernán, 2018; Muñoz et al., in press). Magnetic susceptibility was measured every 50 cm in a 1,371 m-thick stratigraphic column made nearby of Navalsaz (La Rioja), and samples, spaced every meter, taken for carbonate content and colour parameter measurements (CIE L* a* b*) in the laboratory. Continuous quantitative time series were built based on magnetic susceptibility values, total carbonate content, luminosity (L*), as well as red/green (a*) and yellow/blue (b*) coordinates. The spectral analysis of such series reveals the existence of cycles that can be referred to eccentricity, obliquity and precession Milankovitch frequencies

Dysfunctional LAT2 Amino Acid Transporter Is Associated With Cataract in Mouse and Humans.

Cataract, the loss of ocular lens transparency, accounts for ∼50% of worldwide blindness and has been associated with water and solute transport dysfunction across lens cellular barriers. We show that neutral amino acid antiporter LAT2 (Slc7a8) and uniporter TAT1 (Slc16a10) are expressed on mouse ciliary epithelium and LAT2 also in lens epithelium. Correspondingly, deletion of LAT2 induced a dramatic decrease in lens essential amino acid levels that was modulated by TAT1 defect. Interestingly, the absence of LAT2 led to increased incidence of cataract in mice, in particular in older females, and a synergistic effect was observed with simultaneous lack of TAT1. Screening SLC7A8 in patients diagnosed with congenital or age-related cataract yielded one homozygous single nucleotide deletion segregating in a family with congenital cataract. Expressed in HeLa cells, this LAT2 mutation did not support amino acid uptake. Heterozygous LAT2 variants were also found in patients with cataract some of which showed a reduced transport function when expressed in HeLa cells. Whether heterozygous LAT2 variants may contribute to the pathology of cataract needs to be further investigated. Overall, our results suggest that defects of amino acid transporter LAT2 are implicated in cataract formation, a situation that may be aggravated by TAT1 defects

Efficacy of a strategy for implementing a guideline for the control of cardiovascular risk in a primary healthcare setting: the SIRVA2 study a controlled, blinded community intervention trial randomised by clusters

This work describes the methodology used to assess a strategy for implementing clinical practice guidelines (CPG) for cardiovascular risk control in a health area of Madrid

Modifiable risk factors associated with prediabetes in men and women: A cross-sectional analysis of the cohort study in primary health care on the evolution of patients with prediabetes

Background: Prediabetes is a high-risk state for diabetes development, but little is known about the factors associated with this state. The aim of the study was to identify modifiable risk factors associated with the presence of prediabetes in men and women. Methods: Cohort Study in Primary Health Care on the Evolution of Patients with Prediabetes (PREDAPS-Study) is a prospective study on a cohort of 1184 subjects with prediabetes and another cohort of 838 subjects without glucose metabolism disorders. It is being conducted by 125 general practitioners in Spain. Data for this analysis were collected during the baseline stage in 2012. The modifiable risk factors included were: smoking habit, alcohol consumption, low physical activity, inadequate diet, hypertension, dyslipidemia, and obesity. To assess independent association between each factor and prediabetes, odds ratios (ORs) were estimated using logistic regression models. Results: Abdominal obesity, low plasma levels of high-density lipoprotein cholesterol (HDL-cholesterol), and hypertension were independently associated with the presence of prediabetes in both men and women. After adjusting for all factors, the respective ORs (95% Confidence Intervals) were 1.98 (1.41-2.79), 1.88 (1.23-2.88) and 1.86 (1.39-2.51) for men, and 1.89 (1.36-2.62), 1.58 (1.12-2.23) and 1.44 (1.07-1.92) for women. Also, general obesity was a risk factor in both sexes but did not reach statistical significance among men, after adjusting for all factors. Risky alcohol consumption was a risk factor for prediabetes in men, OR 1.49 (1.00-2.24). Conclusions: Obesity, low HDL-cholesterol levels, and hypertension were modifiable risk factors independently related to the presence of prediabetes in both sexes. The magnitudes of the associations were stronger for men than women. Abdominal obesity in both men and women displayed the strongest association with prediabetes. The findings suggest that there are some differences between men and women, which should be taken into account when implementing specific recommendations to prevent or delay the onset of diabetes in adult population

Ribociclib induces broad chemotherapy resistance and EGFR dependency in ESR1 wildtype and mutant breast cancer

While endocrine therapy is highly effective for the treatment of oestrogen receptor-α (ERα)-positive breast cancer, a significant number of patients will eventually experience disease progression and develop treatment-resistant, metastatic cancer. The majority of resistant tumours remain dependent on ERα-action, with activating ESR1 gene mutations occurring in 15–40% of advanced cancers. Therefore, there is an urgent need to discover novel effective therapies that can eradicate cancer cells with aberrant ERα and to understand the cellular response underlying their action. Here, we evaluate the response of MCF7-derived, CRISPR-Cas9-generated cell lines expressing mutant ERα (Y537S) to a large number of drugs. We report sensitivity to numerous clinically approved inhibitors, including CDK4/6 inhibitor ribociclib, which is a standard-of-care therapy in the treatment of metastatic ERα-positive breast cancer and currently under evaluation in the neoadjuvant setting. Ribociclib treatment induces senescence in both wildtype and mutant ERα breast cancer models and leads to a broad-range drug tolerance. Strikingly, viability of cells undergoing ribociclib-induced cellular senescence is maintained via engagement of EGFR signalling, which may be therapeutically exploited in both wildtype and mutant ERα-positive breast cancer. Our study highlights a wide-spread reduction in sensitivity to anti-cancer drugs accompanied with an acquired vulnerability to EGFR inhibitors following CDK4/6 inhibitor treatmen