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Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

This corrects the article DOI: 10.1038/ncomms15908.

This corrects the article DOI: 10.1038/ncomms15908.

Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 5' end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development.

Additive manufacturing is widely used to fabricate metamaterials. The mechanical properties of these are tailored by modifying topological parameters to meet desired performance. Here, an auxetic metamaterial composed of arc-shape elements is presented. The directional dependency of the apparent stiffness was characterized through finite element analysis and tensile and compressive tests on additively manufactured samples with fused filament fabrication in thermoplastic polyurethane. Poisson's ratio was measured with computational vision. The effective Young's modulus resulted with a nonlinear relation to the wall thickness. The orientation sensibility exposed the relevance of rotational symmetry in a lattice architected metamaterial. [ABSTRACT FROM AUTHOR]

Introduction: Ocular trauma is a significant cause of visual loss with long-term sequelae, including reduced quality of life and loss of productivity for young patients. Surgical treatment depends on the injury; enucleation and evisceration are viable options in nonrecoverable eyes. Our study aims to describe the epidemiological and clinical profiles of patients undergoing evisceration/enucleation due to ocular trauma in a tertiary care center in Medellin, Colombia, over 10 years. Methods: We conducted a cross-sectional descriptive study of eyes that were eviscerated or enucleated due to trauma at the SHospital Universitario San Vicente Fundación in Medellin, Colombia, between 2011 and 2021. We studied sociodemographic characteristics, factors related to ocular trauma, and the surgical procedure performed. Results: We studied 161 eyes of 160 patients, of which 2 were enucleated and 158 eviscerated due to ocular trauma. The male-to-female ratio was 7.9:1, and the mean age was 36.6 years (standard deviation = 18.3). 52.2% were due to aggression or violence; the most frequent mechanism was a gunshot wound (28.1%). 98.1% were classified as open ocular trauma, of which 84.5% were ruptured globes. Of the eyes with reported visual acuity, 93.3% did not perceive light. Of the 161 eyes, 58.4% suffered an orbital fracture, and 29.2% suffered cranioencephalic trauma. Primary evisceration was performed in 98.8%, with half of the patients operated in 2 days or less and 75% in 4 days or less. An orbital implant was used in 90.7%. Seventy-five percent of patients were followed up at 36 days. Conclusions: The majority of ocular trauma resulting in loss of the eyeball occurred in young men who had suffered aggression or violence and presented with ocular rupture, with primary evisceration and orbital implant being performed in most cases, in contrast to what is reported in international series where secondary evisceration is preferred, possibly due to the initial severity of the traumatized eyes. [ABSTRACT FROM AUTHOR]

Purpose: To establish the demographic, clinical characteristics, and factors related to the development of eyelid tumors in two ophthalmology services in a Colombian population. Methodology: Retrospective, cross-sectional study of secondary cut, evaluating clinical histories of ophthalmological consultation in two ophthalmological centers in the period of years 2015-2021 with confirmed diagnosis by biopsy of malignant neoplasm of the eyelid, clinical, and demographic variables was identified. Statistical analyses were performed using the SPSS version 20 program. Results: In a 7-year period, a total of 1802 ophthalmology medical records were reviewed, with a prevalence of 6.7 × 1000 population evaluated, an average age of 64.5 years. It was found a greater affectation in the female gender (61.2%). The main consultation symptom was the appearance of an eyelid lesion (83.6%), and the most common histological subtype was basal cell carcinoma (BCC) (66.4%), mainly affecting the right lower eyelid (40.8%). And extending to areas adjacent to the eyelid only in 28.9% of cases, receiving especially surgical management (87.4%). Conclusions: The data found is consistent with other epidemiological studies carried out worldwide on clinical and demographic data of patients affected by malignant eyelid tumors. It mainly affects older populations, being the basal cell histological subtype the most common within our population. Future studies can be carried out on this basis to broaden the knowledge and applicability. [ABSTRACT FROM AUTHOR]

Objectives: to assess the prevalence of maternal gestational anemia and its association with the birth weight. Methods: retrospective longitudinal observational study in a cohort of 370 pregnant women. Anthropometric, biochemical, ginecobstetric and sociodemographic data of both mothers and newborns were evaluated. The results of maternal erythrocyte indices were analyzed and contrasted with newborns anthropometrical data. Results: the mean age of the pregnant women was 27±6 years, with a mean gestational age of 32±6 weeks at the assessment moment, 56.2% were overweight. The prevalence of anemia was 28.6%. 47.2% women with anemia and 36% women without anemia had low birth weight/very low birth weight newborns (p=0.009). Of the children born to mothers with iron deficiency anemia, 20% had low birth weight and 15% very low birth weight. 54.3% newborns with global undernutrition or at risk of developing it were born to women with underweight(p=0.046), in addition, the higher the maternal weight, the lower the number of term newborns with risk of short height (p<0.001). Conclusions: there is relationship between the anemia, the maternal nutritional status and the birth weight. [ABSTRACT FROM AUTHOR]