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The Chilean Patagonian fjords are globally renowned as one of the few remaining pristine environments on Earth; however, their ecosystems are under significant threat from climatic and anthropogenic pressures. Of particular concern is the lack of research into the impact of plastic pollution on the waters and biodiversity of these fjords. In this study, the marine environment of a secluded and sparsely populated fjord system in southern Patagonia was sampled to assess microplastics in seawater, beaches, bottom sediment, and zooplankton. Microplastics were found to be widespread across the water surface of the fjord, but with low abundances of 0.01 ± 0.01 particles m -3 (mean ± SD). The presence of microplastics in sedimentary environments (e.g., beaches and bottom sediments, 15.6 ± 15.3 and 9.8 ± 24 particles kg of dry sediment -1 , respectively) provided additional evidence of plastic debris accumulation within the fjord system. Furthermore, microplastics were already bioavailable to key zooplankton species of the Patagonian food web (0.01 ± 0.02 particles individual -1 ), suggesting bioaccumulation. A comprehensive examination of potential microplastic inputs originating from coastal runoff, coupled with distribution of water masses, suggested minimal local contribution of microplastics to the fjord, strongly indicating that plastic litter is likely entering the area through oceanic currents. The composition and type of microplastics, primarily consisting of polyester fibers (approx. 60 %), provided further support for the proposed distant origin and transportation into the fjord by oceanographic drivers. These results raise significant concern as reveal that despite a lack of nearby population, industrial or agricultural activity, remote Patagonian fjords are still impacted by plastic pollution originating from distant sources. Prioritizing monitoring efforts is crucial for effectively assessing the future trends and ecological impact of plastic pollution in these once so-called pristine ecosystems., Competing Interests: Declaration of competing interest Lara Marcus reports financial support was provided by National Fund For Scientific Technological and Technological Innovation Development. Mauricio A. Urbina reports financial support was provided by National Agency for Research and Development., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To assess the internal consistency, convergent and divergent validity, and concurrent validity of the Tilburg Frailty Indicator (TFI) within community-dwelling older people in Spain, Greece, Croatia, the Netherlands, and the United Kingdom., Design: Cross-sectional study., Setting: Primary care and community settings., Participants: In total, 2250 community-dwelling older people (60.3% women; mean age = 79.7 years; standard deviation = 5.7)., Methods: We assessed the reliability and validity of the full TFI as well as its physical, psychological, and social domains. Baseline data of the Urban Health Centers Europe project were used. The internal consistency was assessed with the Cronbach alpha. The convergent and divergent validity were assessed using Pearson correlation coefficients between the domains and alternative measures: the 12-item short-form, Groningen activity restriction scale, 5-item mental well-being scale of the 36-Item Short Form Survey, and the De Jong Gierveld loneliness scale. The concurrent validity was assessed by the area under the receiver operating characteristic curve with physically frail (Survey of Health, Ageing and Retirement in Europe-Frailty Instrument), loss of independence (Groningen activity restriction scale), limited function (Global Activity Limitation Index), poor mental health (5-item mental well-being scale of the 36-Item Short Form Survey), and feeling lonely (De Jong Gierveld loneliness scale) as criteria., Results: The internal consistency of the full TFI was satisfactory with the Cronbach alpha ≥0.70 in the total population and in each country. The internal consistency of the psychological and social domains was not satisfactory. The convergent and divergent validity of the physical, psychological, and social domains was supported by all the alternative measures in the total population and in each country. The concurrent validity of the full TFI and the physical, psychological, and social domains was supported with most area under the receiver operating characteristic curve ≥0.70 in the total population and in each country., Conclusions and Implications: The TFI is a reliable and valid instrument to assess frailty in community-dwelling older people in Spain, Greece, Croatia, the Netherlands, and the United Kingdom., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Thanks to modern treatment with all-trans retinoic acid and chemotherapy, acute promyelocytic leukemia (APL) is now the most curable type of leukemia. However, this progress has not yielded equivalent benefit in developing countries. The International Consortium on Acute Promyelocytic Leukemia (IC-APL) was established to create a network of institutions in developing countries that would exchange experience and data and receive support from well-established US and European cooperative groups. The IC-APL formulated expeditious diagnostic, treatment, and supportive guidelines that were adapted to local circumstances. APL was chosen as a model disease because of the potential impact on improved diagnosis and treatment. The project included 4 national coordinators and reference laboratories, common clinical record forms, 5 subcommittees, and laboratory and data management training programs. In addition, participating institutions held regular virtual and face-to-face meetings. Complete hematological remission was achieved in 153/180 (85%) patients and 27 (15%) died during induction. After a median follow-up of 28 months, the 2-year cumulative incidence of relapse, overall survival (OS), and disease-free survival (DFS) were 4.5%, 80%, and 91%, respectively. The establishment of the IC-APL network resulted in a decrease of almost 50% in early mortality and an improvement in OS of almost 30% compared with historical controls, resulting in OS and DFS similar to those reported in developed countries.

Background: Dietary phytosterols are a recommended therapeutic option for decreasing plasma cholesterol. The increased activity of ATP-binding cassette (ABC) transporters ABCA1, ABCG5 and ABCG8, or, alternatively, a decrease in Niemann-Pick C1 Like 1 (NPC1L1) could mediate the reduction in intestinal cholesterol absorption caused by phytosterols. Other biological properties such as a direct immune modulatory activity have recently been ascribed to these plant compounds., Methods: To gain insight into the molecular effects of phytosterols, global genome-wide gene profiling and real-time RT-PCR studies were conducted in small intestines and livers of phytosterol-treated apolipoprotein E-deficient (apoE(-/-)) mice. Re-testing of the main results was performed in C57BL/6J and LDL receptor-deficient (LDLR(-/-)) mice., Results: Intestinal cholesterol absorption was decreased in all mouse models but plasma cholesterol was only decreased in apoE(-/-) and LDLR(-/-) mice. ABCA1, ABCG5, ABCG8 and NPC1L1 mRNA levels were slightly reduced in the intestine of phytosterol-treated apoE(-/-) and LDLR(-/-) mice, but increased in C57BL/6J-treated mice. Phytosterols changed genes involved in immune regulation in apoE(-/-) mice. However, these changes were less extensive in LDLR(-/-) mice and were not found in C57BL/6J mice., Conclusions: Inhibition of intestinal cholesterol absorption by phytosterols is not mediated via transcriptional changes in ABCA1, ABCG5, ABCG8 or NPC1L1. Changes suggestive of immunomodulation are associated with the hypocholesterolemic effect of phytosterols and with apoE deficiency.