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The Spanish Society of Medical Oncology (SEOM) last published clinical guidelines on venous thromboembolism (VTE) and cancer in 2019, with a partial update in 2020. In this new update to the guidelines, SEOM seeks to incorporate recent evidence, based on a critical review of the literature, to provide practical current recommendations for the prophylactic and therapeutic management of VTE in patients with cancer. Special clinical situations whose management and/or choice of currently recommended therapeutic options (low-molecular-weight heparins [LMWHs] or direct-acting oral anticoagulants [DOACs]) is controversial are included., (© 2024. The Author(s).)

Objectives: To analyze the clinical profile, adequacy of treatment with rivaroxaban and outcomes in octogenarians with atrial fibrillation (AF), taking rivaroxaban in clinical practice., Methods: Observational and non-interventional study that included AF adults recruited from 79 Spanish centers, anticoagulated with rivaroxaban ≥ 6 months before being included. Data were analyzed according to age (≥ 80 vs . < 80 years) at baseline., Results: Out of 1433 patients, 453 (31.6%) were octogenarians at baseline. Compared to younger patients, octogenarians had more comorbidities, higher CHA 2 DS 2 -VASc (4.5 ± 1.3 vs . 3.0 ± 1.4; P < 0.001) and HAS-BLED scores (2.0 ± 1.0 vs. 1.4 ± 1.0; P < 0.001). Overall, the dose of rivaroxaban was adequately prescribed in 83.4% of patients, but more frequently in the younger population (71.1% vs. 89.1%; P = 0.039). After a mean follow-up of 2.2 ± 0.6 years, annual rates of stroke + systemic embolism + transient ischemic attack, MACE, cardiovascular death and major bleeding were 1.03%, 1.24%, 1.03% and 1.75%, respectively, in octogenarian patients. Except for progressive heart failure death and major bleeding, rates of outcomes in octogenarians were similar compared to younger patients. In octogenarians, the concomitant use of antiplatelet agents and non-severe dementia were independently associated with the development of ischemic stroke, whereas previous coronary revascularization and heart failure with MACE, and higher HAS-BLED score with major bleeding., Conclusions: In clinical practice, around one third of patients taking rivaroxaban are octogenarians. These patients have many comorbidities and a high thromboembolic risk. Despite that, rates of adverse events remain low. Rivaroxaban is adequately prescribed in the majority of octogenarians., Competing Interests: Francisco Marín has received consultancy/lecturing fees from Bayer, Boehringer Ingelheim, Pfizer, Bristol Myers Squibb, Daiichi Sankyo and AFNET. Manuel Anguita Sánchez has received funding for consulting and conference services from Bayer, Daiichi-Sankyo and Pfizer. Iñaki Lekuona has received honoraria for presentations from Bayer, Boehringer-Ingelheim, Daiichi Sankyo and Pfizer-BMS. Marcelo Sanmartin Fernández has received speaker and advisory fees from the following companies in the past 3 years: Bayer, Boehringer Ingelheim, BMS and Pfizer. Vivencio Barrios has received consultancy/lecture fees from Bayer, BMS/Pfizer, Boehringer Ingelheim and Daiichi Sankyo. Juan Cosín-Sales has received consultancy/lecture fees from Bayer, BMS/Pfizer, Boehringer Ingelheim and Daiichi Sankyo. Alejandro I. Pérez Cabeza has received personal fees for educational activities or participation on boards from Daiichi Sankyo, Bayer, Boehringer Ingelheim and Bristol Myers Squibb. Vanesa Roldán Schilling has received honoraria for presentations from Bayer, Boehringer-Ingelheim, Daiichi Sankyo and Pfizer-BMS. Carles Rafols Priu is an employee Bayer Hispania SL. Carlos Pérez Muñoz, Esteban Orenes-Piñero and María Asunción Esteve Pastor declared no personal conflict of interest or financial fees related with the manuscript., (© 2024 JGC All rights reserved; www.jgc301.com.)

The brain constitutes a good example of a chaotic, nonlinear biological system where large neuronal networks operate chaotically with random connectivity. This critical state is significantly affected by the anesthetic loss of consciousness induced by drugs whose pharmacological behavior has been classically based on linear kinetics and dynamics. Recent developments in pharmacology and brain monitoring during anesthesia suggest a different view that we tried to explore in this article. The concepts of effect-site for hypnotic drugs modeling a maximum effect, electroencephalographic dynamics during induction, maintenance, and recovery from anesthesia are discussed, integrated into this alternative view, and how it may be applied in daily clinical practice., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The aim of this study was to explore the efficacy, safety, and pain level of granulocyte colony-stimulating factor (G-CSF) administration via a subcutaneous catheter compared with direct injection in children with cancer. Method: This was a pilot randomized controlled trial of standard G-CSF administration versus subcutaneous catheter administration. Children 2-15 years of age who were beginning G-CSF after their first chemotherapy cycle and anticipated to receive G-CSF following the next three cycles of chemotherapy were eligible. Efficacy, safety, and pain were as outcomes of the study. Results: Twenty-nine children with cancer (median age 12 years) were enrolled in the study (16 children in the subcutaneous catheter group and 13 children in the direct injection group). During Cycle 2, the median number of days to reach absolute neutrophil count (ANC) ≥ 500/mm 3 was greater among those in the subcutaneous catheter group (12 vs. 10; p   =  .02). In Cycle 3, however, the subcutaneous catheter group received fewer doses of G-CSF (8 vs. 12; p   =  .004). No complications related to subcutaneous catheter use were observed. No differences in the visual analog scale pain score were observed between groups in Cycles 1 to 3; however, in Cycle 4, children in the subcutaneous catheter group had lower median pain scores than those in the direct subcutaneous injection group ( Mdn   =  0, [IQR]  =  0-2 vs. Mdn   =  1, IQR  =  0-6; p  < 0.01). Conclusion: Results demonstrated administering G-CSF via a subcutaneous catheter enables ANC to recover with no pain or complications associated with its use. Thus, oncology teams may consider this administration method to be used in children with cancer., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Hyperlipidemia is the main underlying cause of atherosclerotic cardiovascular disease. Reducing low-density lipoprotein (LDL) cholesterol to recommended targets after an acute coronary syndrome (ACS) is of utmost importance as it is associated with a reduction of mortality and further cardiovascular events. Unfortunately, there are considerable gaps between guideline recommendations and clinical practice. In addition, the approach to treatment of this population is very heterogeneous, even in specialized cardiovascular units. Some easy-to-implement strategies may help to optimize the management of these patients., Areas Covered: The OPTA Project was developed to identify these gaps and to provide recommendations to improve and harmonize the management of patients with ACS, with a specific focus on lipids., Expert Opinion: Five areas of interest were defined: 1) evaluation of cardiovascular risk at admission, 2) development of a strategy to effectively and rapidly reduce LDL cholesterol levels, 3) determining LDL cholesterol goals (<55 mg/dL or stricter) and follow-up, 4) data collection during hospitalization, and 5) standardized discharge report. Specific recommendations are given to reduce inequalities, following the targets 'the lower, the better' and 'the earlier, the better.'

Aim: It is not well known how comorbidities may change the prognosis of atrial fibrillation (AF) patients. This study was aimed to analyze the impact of cardiovascular disease on this population. Materials & methods: EMIR was a multicenter, prospective study, including 1433 AF patients taking rivaroxaban for ≥6 months. Data were analyzed according to the presence of vascular disease. Results: Coronary artery disease was detected in 16.4%, peripheral artery disease/aortic plaque in 6.7%, vascular disease in 28.3%. Patients with coronary artery disease had higher rates (per 100 patient-years) of major adverse cardiovascular events (2.98 vs 0.71; p < 0.001) and cardiovascular death (1.79 vs 0.41; p = 0.004). Those with vascular disease had higher rates of thromboembolic events (1.47 vs 0.44; p = 0.007), major adverse cardiovascular events (2.03 vs 0.70; p = 0.004), and cardiovascular death (1.24 vs 0.39; p = 0.025). Patients with peripheral artery disease/aortic plaque had similar rates. Conclusion: AF patients with vascular disease have a higher risk of non-embolic outcomes.

We model the nocturnal patterns of the main vector of Leishmania braziliensis (Vianna) in the Paranaense region of South America, Nyssomyia whitmani (Antunes & Coutinho). Occurrence and abundance variation were analyzed by hourly periods, and in relation to sunrise and sunset to avoid differences in luminosity at fixed times throughout the year. The possible role of climatic and environmental variables on nocturnal activity curves was explored. A rotating light trap was operated biweekly in the peridomestic henhouse of a farm in Puerto Iguazú, from May 2016 to May 2018. Ny. whitmani, is the predominant Phlebotominae species (6,720 specimens captured), and is present throughout the night and seasons. Generalized additive models of nocturnal abundance of Ny. whitmani show a bell shape with an acrophase in the early evening. Models of abundance distribution as a function of total abundance showed significant nonlinear variations, only for the tertile of highest vector abundance, in the curves by hourly periods, and related to dawn, while female abundance relative to total abundance showed an asymptotic increasing curve, suggesting density-dependent events with abundance thresholds. Finally, temperature was the variable that best explained the pattern of abundance distribution of Ny. whitmani during the night, although triggers for scotophase activity due to internal clocks or luminosity could not be ruled out. The relationship of activity and abundance with climatic variables would also explain the nights of extraordinary abundance, and therefore of greater probability of vector-human and vector-reservoir contacts., (© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To analyze the effectiveness and safety of rivaroxaban in patients with atrial fibrillation (AF). Methods: The clinical profile and outcomes of the EMIR study were indirectly compared with those of ROCKET-AF, eight other Spanish observational studies and XANTUS. Results: In EMIR, mean age was 74.2 years and CHA 2 DS 2 -VASc was 3.5. In the rivaroxaban arm of the ROCKET-AF trial, mean age was 73 years and CHADS 2 was 3.5, whereas in the Spanish studies mean age ranged from 74.9 years to 78.4 years and CHA 2 DS 2 -VASc from 3.5 to 4.3. In EMIR, rates of stroke/systemic embolism, major adverse cardiovascular events, cardiovascular death and major bleeding were 0.57, 1.07, 0.63 and 1.04 events/100 patient-years, respectively. In ROCKET-AF, these numbers were 1.7, 3.91, 1.53 and 3.6 events/100 patient-years, respectively. In the Spanish studies, rates of stroke and major bleeding were 0-1.8 and 0.22-4.2 events/100 patient-years, respectively. In XANTUS, rates of stroke, major adverse cardiovascular events and major bleeding were 0.7, 1.8 and 2.1 events/100 patient-years, respectively. Conclusion: Despite the fact that rivaroxaban is prescribed for elderly patients with a high thromboembolic risk, rates of outcomes remain low.

Background: Pancreatic carcinoma is one of the tumors associated with a higher risk for thromboembolic events, with incidence rates ranging from 5% to 41% in previous retrospective series., Patients and Methods: We conducted a retrospective study in eleven Spanish hospitals that included 666 patients diagnosed with pancreatic carcinoma (any stage) between 2008 and 2011 and treated with chemotherapy. The main objective was to evaluate the incidence of venous thromboembolic events (VTE) in this population, as well as potential risk factors for thrombosis. The impact of VTE on mortality was also assessed., Results: With a median follow-up of 9.3 months, the incidence of VTE was 22.1%; 52% were diagnosed incidentally. Our study was unable to confirm the ability of the Khorana score to discriminate between patients in the intermediate or high risk category for thrombosis. The presence of VTE proved to be an independent prognostic factor associated with increased risk of death (HR 2.39, 95% CI 1.96-2.92). Symptomatic events correlated with higher mortality than asymptomatic events (HR 1.72; 95% CI, 1.21-2.45; p = 0.002), but incidental VTE, including visceral vein thrombosis (VVT), negatively affected survival compared to patients without VTE. Subjects who developed VTE within the first 3 months of diagnosis of pancreatic carcinoma had lower survival rates than those with VTE after 3 months (HR 1.92, 95% CI 1.30-2.84; p&lt;0.001)., Conclusions: Pancreatic carcinoma is associated with a high incidence of VTE, which, when present, correlates with worse survival, even when thrombosis is incidental. Early onset VTE has a particularly negative impact., (Copyright © 2022. Published by Elsevier B.V.)

Negative emotional states (NES; i.e., depression, anxiety and stress) are likely contributors to the development of food addiction (FA). The association between NES and FA symptoms may be mediated by altered eating behaviors or by eating-to-cope motives. This study examined, in a sample of Argentinean young adults, the association between NES and FA symptoms via eating-to-cope motives and three patterns of eating behaviors. We also examined whether the model was invariant across college status. The transition from high school to college is usually associated with increased exposure to stress, which promotes the probability of engaging in altered eating behaviors. A sample of 499 Argentinean young adults (mean age = 24.9 ± 3.51 years) completed a survey that assessed FA symptoms, eating behaviors (i.e., uncontrolled, emotional, and restrained eating), eating-to-cope motives and NES. A path analysis tested the indirect association between NES and FA symptoms via uncontrolled, emotional or restrained eating, or by eating-to-cope. Stress and depression symptoms were indirectly associated with FA symptoms via uncontrolled eating and eating-to-cope motives. The model was invariant across college status. The findings suggest that NES are associated with FA symptoms by increasing uncontrolled eating and eating-to-cope motives. Young adults exhibiting greater depressive or stress symptoms, higher eating-to-cope, or higher uncontrolled eating may be at risk for FA. Future research should examine the significance of this pattern by tailoring interventions to these characteristics., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The evolution of Thalattosuchia documents the unique shift among Crocodylomorpha from aquatic continental/coastal habitats to a fully pelagic lifestyle. This transition was coupled with deep modification of their skeletons, such as hydrofoil forelimbs, hypocercal tail, and loss of osteoderms. The natural snout casts of the rhacheosaurin Cricosaurus araucanensis showed that it also included changes in the internal anatomy of the snout like the enlargement of nasal glands (probably for salt excretion) and the rearrangement of the paranasal sinus system, including the internalization of the antorbital sinus. Here we described the snout natural cast of the geosaurin Dakosaurus andiniensis from the Late Jurassic of Patagonia. The information provided by it indicates that, despite having different external morphologies and ecology, D. andiniensis and C. araucanensis share the same facial anatomy. The new cast preserves a suborbital diverticulum of the antorbital sinus protruding into the orbit through the postnasal fenestra. Its location indicates that it was interleaved with jaw adductor muscles suggesting an active airflow in the paranasal sinus. We provide a putative functional interpretation of this peculiar arrangement where bellow pumps actions of musculature may help drain salt glands. The rearrangement of the paranasal sinuses predates the transition to a completely pelagic-lifestyle. We proposed a stepwise evolutionary scenario of Thalattosuchia, implying changes in the preorbital region (and orbit orientation) where the internalized antorbital sinus via its subsidiary diverticulum was co-opted for helping nasal glands drainage. Further scrutiny of facial anatomy of a larger sample of thalattosuchians will help to test this hypothesis., (© 2021 American Association for Anatomy.)

Metal-halide perovskite nanocrystals have demonstrated excellent optoelectronic properties for light-emitting applications. Isovalent doping with various metals (M 2+ ) can be used to tailor and enhance their light emission. Although crucial to maximize performance, an understanding of the universal working mechanism for such doping is still missing. Here, we directly compare the optical properties of nanocrystals containing the most commonly employed dopants, fabricated under identical synthesis conditions. We show for the first time unambiguously, and supported by first-principles calculations and molecular orbital theory, that element-unspecific symmetry-breaking rather than element-specific electronic effects dominate these properties under device-relevant conditions. The impact of most dopants on the perovskite electronic structure is predominantly based on local lattice periodicity breaking and resulting charge carrier localization, leading to enhanced radiative recombination, while dopant-specific hybridization effects play a secondary role. Our results suggest specific guidelines for selecting a dopant to maximize the performance of perovskite emitters in the desired optoelectronic devices.

Aims: Severe tricuspid regurgitation (TR) has adverse effects on outcomes, with limited therapeutic options. We report the outcomes of patients undergoing percutaneous annuloplasty as a treatment of  ≥severe functional TR in a single centre., Methods and Results: Prospective, single-arm, single-centre study that enrolled 24 consecutive patients with at least severe functional TR undergoing percutaneous annuloplasty with Cardioband system between 2019 and 2021. Clinical and echocardiographic data were prospectively collected, with a mean follow-up of 279 ± 246 days. At baseline, 66.6% were in New York Heart Association (NYHA) Classes III and IV and 100% had significant oedema. Technical success was 91.6%. At the end of follow-up, there was one death. Echocardiography showed a significant reduction in septolateral annular diameter of 10.4 mm (P < 0.001) that remained stable at the end of follow-up. The severity of the TR was also reduced. About 81.8% of patients were in NYHA Classes I and II. The number of patients with significant oedema decreased to 46% (P = 0.01). Six-minute walk distance improved by 68.8 m (P = 0.12)., Conclusion: Percutaneous annuloplasty with Cardioband system is an effective and safe treatment for patients with symptomatic, ≥severe functional TR. Annular reduction and TR severity reduction remained significant and sustained for 1 year. Patients experienced improvements in quality of life and exercise capacity., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The Snow Hill Island Formation (SHIF; late Campanian - early Maastrichtian) crops out in the northeast of the Antarctic Peninsula and constitutes the basal part of the late Campanian-early Maastrichtian sedimentary succession of the James Ross Basin (NG Sequence). Its major exposures occur at the James Ross and Vega islands. Several fossil-bearing localities have been identified in the SHIF providing a valuable fauna of invertebrates and vertebrates, and flora. Our study focuses on the vertebrate fauna recovered at Gamma and Cape Lamb members of the SHIF. The marine vertebrate assemblages include chondrichthyans, actinopterygians, and marine reptiles (elasmosaurid plesiosaurs and mosasaurs). A diverse terrestrial vertebrate assemblage has been reported being characterized by dinosaurs (sauropod, elasmarian ornithopods, nodosaurid ankylosaur, and a paravian theropod), pterosaurs and birds. Most SHIF dinosaurs share close affinities with penecontemporaneous taxa from southern South America, indicating that at least some continental vertebrates could disperse between southern South America and Antarctica during the Late Cretaceous. The Snow Hill Island Formation provides the most diverse Late Cretaceous marine and continental faunas from Antarctica. The present study summarizes previous and new vertebrate findings with the best actualized stratigraphical framework, providing a more complete fauna association and analyzing further perspectives.

Background: Early-life adversity impacts on the offspring's brain development and is associated with a higher risk of developing age-associated diseases. In particular, perinatal protein malnutrition appears to be one of the most critical nutritional deficiencies affecting the individual's health and survival, but little is known about its effects on the persistence of behavioral alterations throughout life. Thus, the aim of the present study was to investigate how perinatal protein malnutrition impacts on age-related changes in the neuromuscular, cognitive and behavioral functions throughout life in a mouse model., Methods: One group of CF-1 dams received a normal-protein diet (NP: 20% casein) during gestation and lactation, whereas another group received a low-protein diet (LP: 10% casein). The offspring of both groups were analyzed by means of several behavioral tests at four different ages (young: 6-10 weeks old, mature: 22-26 weeks old, middle age: 39-43 weeks old, and old: 55-59 weeks old)., Results: Regarding neuromuscular functions, LP mice showed an early deterioration in muscular strength and a reduction in the body weight throughout life. Regarding behavior, while NP mice showed an age-related reduction of exploratory behavior, LP mice showed a constantly low level of this behavior, as well as high anxiety-like behavior, which remained at high levels throughout life. Regarding cognitive functions, LP mice showed deteriorated working memory at middle age. Finally, LP mice died 3.4 times earlier than NP mice. Analysis of the sex-related vulnerability showed that females and males were equally affected by perinatal protein malnutrition throughout life., Conclusion: Our results demonstrate that perinatal protein malnutrition induces enduring and age-related impairment behaviors, which culminate in higher death risk, affecting males and females equally.

Background: Healthcare personnel are often at high risk of contamination when participating in airway management and other aerosol-generating procedures., Aim: To explore the differences in self-contamination after removal of gown and coverall personal protective equipment (PPE) using an ultraviolet-fluorescent solution., Methods: This prospective, randomized, controlled crossover trial was set in a third-level university health centre in Buenos Aires, Argentina between August and October 2020. The study included 60 anaesthesia personnel volunteers, and no participants were excluded from the study. A two-period/two-intervention design was chosen; each intervention comprised audio-guided placement of PPE, full-body spraying of fluorescent solution, audio-guided removal of PPE, and self-contamination assessment through ultraviolet light scanning. The primary outcome was the mean within-participant difference (any traces) between PPE suits. Statistical significance was tested using t-tests for paired data. The allocation ratio was 25/35 (gown followed by coverall/coverall followed by gown)., Findings: Self-contamination after removal of coveralls was greater than that after removal of gowns, with a mean within-participant difference of 11.45 traces (95% confidence interval 8.26-14.635; P<0.001). Significant differences were found for the number of self-contaminated body zones, small fluorescent traces and large fluorescent traces. Removal of a gown was associated with a markedly lower risk of self-contamination., Conclusions: Quick one-step removal of a gown and gloves may reduce self-contamination in the arm/hand area. Fluorescent solutions can help to identify self-contamination and compare outcomes between available PPE suits. Repeated training sessions and enhanced knowledge on self-contamination following removal of PPE are paramount., Clinical Trial Registration Number: NCT04763304 (on ClinicalTrials.gov)., (Copyright © 2021 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Aim: To analyze the frequency and variables related to inappropriate rivaroxaban dosage in clinical practice and its impact on outcomes after 2 years. Materials & methods: Postauthorization, observational, multicenter study, in which atrial fibrillation patients, treated with rivaroxaban ≥6 months were included. Results:  A total of 1421 patients (74.2 ± 9.7 years, CHA 2 DS 2 -VASc 3.5 ± 1.6) were included. Overall, 22.9% received rivaroxaban 15 mg. The proper dose of rivaroxaban was taken by 83.3% (9.7% underdosed, 7.0% overdosed). Older age and renal insufficiency were associated with inadequate rivaroxaban dosage. There was a trend toward higher all-cause mortality among underdosed patients (adjusted hazard ratio 1.39; 95% CI 0.75-2.58), and more bleedings in overdosed patients (2.29 vs 0.80 events/100 patient-years; p = 0.14). Conclusion: In clinical practice, rivaroxaban is properly dosed in most patients.

In recent decades, eggshells of eggs from large-bodied reptiles have been studied by many researchers, to describe the eggshell, to compare them to extinct lineages that once inhabited our planet and also to understand how the egg provides the embryo specific conditions during incubation. In previous studies we described and characterized normal and pathologic Caiman latirostris eggshells; we also evaluated how the eggshell changes during incubation. In a study relating temperature variation and eggshell structures of successful eggs, we observed empty structures not previously described that we termed "intracascaral space". The aim of this study is to describe this structure of C. latirostris eggshells. We hypothesize about the possible functions which it would perform during incubation and for development of the embryos.

Background: Healthcare systems are under prominent stress due to the COVID-19 pandemic. A fast and simple triage is mandatory to screen patients who will benefit from early hospitalization, from those that can be managed as outpatients. There is a lack of all-comers scores, and no score has been proposed for western-world population., Aims: To develop a fast-track risk score valid for every COVID-19 patient at diagnosis., Methods: Single-center, retrospective study based on all the inhabitants of a healthcare area. Logistic regression was used to identify simple and wide-available risk factors for adverse events (death, intensive care admission, invasive mechanical ventilation, bleeding > BARC3, acute renal injury, respiratory insufficiency, myocardial infarction, acute heart failure, pulmonary emboli, or stroke)., Results: Of the total healthcare area population, 447.979 inhabitants, 965 patients (0.22%), were diagnosed with COVID-19. A total of 124 patients (12.85%) experienced adverse events. The novel SODA score (based on sex, peripheral O 2 saturation, presence of diabetes, and age) demonstrated good accuracy for adverse events prediction (area under ROC curve 0.858, CI: 0.82-0.98). A cut-off value of ≤2 points identifies patients with low risk (positive predictive value [PPV] for absence of events: 98.9%) and a cut-off of ≥5 points, high-risk patients (PPV 58.8% for adverse events)., Conclusions: This quick and easy score allows fast-track triage at the moment of diagnosis for COVID-19 using four simple variables: age, sex, SpO 2 , and diabetes. SODA score could improve preventive measures taken at diagnosis in high-risk patients and also relieve resources by identifying very low-risk patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Leishmaniases are a global health problem and in Argentina are considered emerging diseases. The new transmission scenarios of tegumentary leishmaniasis are especially important given that large areas of forest are being transformed into rural and urban systems. The aim of this study was to analyze the impact of the construction of a large public building and a neighborhood on the assemblage of Phlebotominae in a rural area with forest remnants and to correlate the changes observed in the species assemblage with characteristics of the environment. Entomological surveys with light traps were conducted on the construction campus in the northeastern region of Argentina at six sites representing different environmental situations. Structural environmental characteristics and meteorological conditions were recorded and analyzed. At least 16 species of Phlebotominae sand flies were collected, the most prevalent being Nyssomyia whitmani (Antunes & Coutinho), followed by the genus Brumptomyia (França & Parrot) and Migonemyia migonei (França). Our study provides evidence of how the structure of the assemblages and prevalent species respond to anthropogenic disturbances. As the construction progressed, both Ny. whitmani and the genus Brumptomyia were favored. The genus Brumptomyia was favored at sites surrounded by high proportions of forest, within patches of remnant vegetation, and relatively far from anthropogenic disturbances, while Ny. whitmani, the main vector of tegumentary leishmaniasis in the region, increases their abundant at short and intermediate distances from vegetation margins and areas close to anthropogenic disturbances, therefore increasing the risk of human exposure to vectors., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In South America, cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) are emerging diseases, expanding in the border area of Argentina, Brazil and Paraguay. Outbreaks of CL were reported since the 1990s, with Nyssomyia whitmani as the main vector in this region. Regarding VL, urban reports started in 2010 with Lutzomyia longipalpis as the main vector. The aim of this study was to evaluate environmental determinants related to the main vectors of leishmaniasis, to contribute to the prevention and control response to the emergence of VL and CL in the Argentina-Brazil-Paraguay border region., Methods: The cross-sectional survey includes two cities and two close rural areas in the Argentinean Northeast Region, between November 2014 and January 2015, with a total of 95 sampling sites. REDILA-BL traps were set for three consecutive nights, and a total of 68 meso- and microscale environmental and landscape characteristics were surveyed. The association between vector abundance with different variables was evaluated using a generalized linear model with zero-inflated negative binomial distribution. We analyzed females for detection of Leishmania DNA., Results: The analysis for Lu. longipalpis indicates an excess of absences when the mean NDWI around the sites were higher. The abundance of Lu. longipalpis at mesoscale level was higher when more urban services were present, and when blood sources such as chickens or dogs at the microscale level were present. For Ny. whitmani, no variable was found to be associated with the absences, while its abundance increased in association with the following variables: percentage of tree cover, presence of garbage collection service, hosted people and, at microscale, the presence of poultry. Leshmania infantum DNA was detected in 2/49 (4%) Lu. longipalpis., Conclusions: The abundance of both species is influenced by variables at different scales, their influence probably has a hierarchy and they are acting on different aspects of the biology of these vectors. The urban spatial segregation of Lu. longipalpis and the peri-urban and rural segregation of N. whitmani increase the risk of VL and CL. The selection of the better variables for each scale will allow the design of appropriate control strategies depending on species.

Background : Discriminating between adolescents who will eventually have ethanol use problems from those who do not is important. Environmental enrichment is a promising approach to reduce drug-related problems, but its impact on ethanol's effects and intake is being scrutinized. Objective : We tested the effects of environmental enrichment on ethanol intake, preference, and anxiety-like response as well as shelter seeking and risk-taking behaviors. Methods : Experiment 1 examined ethanol intake, preference, and anxiety-like responses in 46 male and 54 female Wistar rats that were derived from a short-term breeding program that selected for high and low ethanol drinking during adolescence (ADHI 2 and ADLO 2 lines, respectively). Shelter-seeking and risk-taking behaviors were assessed (Experiment 2) in ADHI 2 and ADLO 2 rats (73 males, 76 females) reared under environmental enrichment or standard housing conditions and given doses of ethanol (2.5 g/kg, intraperitoneal) for 3 weeks. Environmental enrichment was applied on postnatal days 21-42. Ethanol intake was measured on postnatal days 42-68. Anxiety-like behavior and exploratory responses were assessed using the light-dark box and multivariate concentric square field test. Results : In Experiment 1, environmental enrichment increased ethanol intake in female, but not male, ADHI 2 and ADLO 2 rats (p < 0.05). In the baseline measurement of Experiment 2, ADHI 2 rats exhibited reduced risk-taking and increased anxiety-like behavior (p < .05). After exposure to environmental enrichment the ADHI and ADLO rats, both males and females, exhibited increased risk-taking and exploratory behavior (p < 0.05). Conclusions : Environmental enrichment appears to increase ethanol intake in female rats by promoting the exploration of new environments or stimuli. The findings indicate that environmental enrichment increased ethanol intake in female, but not male, rats. Clinical programs that treat alcohol use disorder by emphasizing environmental stimulation should be designed with caution.

The application of network methodology in anatomical structures offers new insights on the connectivity pattern of skull bones, skeletal elements and their muscles. Anatomical networks helped to improve our understanding of the water-to-land transition and how the pectoral fins were transformed into limbs via their modular disintegration. Here, we apply the same methodology to tetrapods secondarily adapted to the marine environment. We find that these animals achieved their return to the sea with four types of morphological changes, which can be grouped into two different main strategies. In all marine mammals and the majority of the reptiles, the fin is formed by the persistence of superficial and interdigital connective tissues, like a 'baby mitten', whereas the underlying connectivity pattern of the bones does not influence the formation of the forefin. On the contrary, ichthyosaurs 'zipped up' their fingers and transformed their digits into carpal-like elements, forming a homogeneous and better-integrated forefin. These strategies led these vertebrates into three different macroevolutionary paths exploring the possible spectrum of morphological adaptations.

Historically, the roots of alcoholism have been linked to either environment or heredity. However, the interaction between these factors is still largely unexplored. The evidence supports a link between alcohol consumption and the endogenous opioid system. We here studied the opioid genes expression in male and female Wistar rats derived from a short-term breeding program which selected -- at adolescence -- for high (ADHI line) or low (ADLO line) ethanol drinking. Specifically, in this work we analyzed central opioid gene expression in the rats of the second filial generation (S 2 -ADLO and S 2 -ADHI). Selective downregulation of pronociceptin (Pnoc) and its receptor (Oprl1) mRNA levels were observed in the prefrontal cortex of male S 2 -ADHI rats when compared to S 2 -ADLO, and for Oprl1 also in the nucleus accumbens. An increase in gene expression was instead observed for pro-opiomelanocortin (Pomc) in the nucleus accumbens of S 2 -ADHI males when compared to S 2 -ADLO, as well as for mu opioid receptor (Oprm1) but in females. The differences in mRNA levels may be due to the different alcohol consumption between the two groups of rats or may represent pre-existing differences between them. Moreover, we show a sex-specific modulation of the expression of these genes, thus pointing out the importance of sex on ethanol responses. The results might lead to more specific and effective pharmacological treatments for alcoholism., Competing Interests: Declaration of Competing Interest We declare having no conflict of interest related to our MS or its results., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To estimate trends in the prevalence of child stunting in the population of children under 5 years of age covered by public health programmes, between 2009 and 2014 in Misiones, Argentina., Methods: Using Bayesian model-based geostatistics, we evaluated 724 872 anthropometric measurements corresponding to 110 633 children. In order to identify disparities at local scale, we evaluated the hypotheses of a differential reduction of stunting according to the geographical location (at two-level spatial resolution) and to the socioeconomic level in a rural or urban environment., Results: The prevalence of stunting had fallen significantly in the province overall. Sex and age defined gender disparities at individual level, and there were regional disparities with higher prevalence values in the north and northeast regions. In these areas, stunting decreased to a greater degree during the studied period, although the spatial pattern remained smoother. Stunting increased in peripheral urban and dispersed rural areas that are socioeconomically vulnerable., Conclusions: The spatial multi-level geostatistical estimates of child undernutrition provide a precision public health tool to target public policies to those populations with the greatest need, in order to reduce health disparities., (© 2020 John Wiley & Sons Ltd.)

We aimed to evaluate brachial and central blood pressure (BP) estimates and biomarker levels in lacunar ischemic stroke (IS) and other IS subtypes (nonlacunar stroke). We studied 70 functionally independent subjects consecutively admitted to our institution after a first episode of IS. Subjects with previous heart failure were excluded. BP was measured at admission and during the subacute phase of stroke (5-7 days after stroke onset). Aortic pulse wave velocity (aPWV), augmentation index (AIx), and 24 h brachial and central BP (24h-ABPM) were measured by means of a Mobil-O-Graph device during the subacute phase of stroke. Determination of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), urinary albumin excretion, and echocardiography were performed in all subjects. After adjusting for age and clinical severity, lacunar IS had significantly higher levels of BP at admission (systolic BP 173 ± 37 vs 153 ± 28 mmHg, p = 0.006; diastolic BP: 97 ± 21 vs 86 ± 16 mmHg, p = 0.035) and during the subacute phase of stroke (systolic BP 152 ± 23 vs 134 ± 19 mmHg, p = 0.001; diastolic BP: 84 ± 14 and 77 ± 10 mmHg, respectively; p = 0.038) but lower NT-proBNP levels (median: 36,277 vs 274 pg/mL, p = 0.009) than nonlacunar IS. Central BP, aPWV, and AIx were not different between lacunar and nonlacunar IS, neither the rate of target organ damage. In conclusion, patients with a first episode of lacunar IS have higher BP values at admission and during the subacute phase of stroke and lower levels of NT-proBNP, suggesting a closer relationship with hypertension of this IS subtype.

Ethanol use is widespread in adolescents, yet only some transition to problematic drinking. It is important to understand why the risk for problematic drinking varies across sub-groups of adolescents. This study reports a short-term selection program to generate Wistar rat lines (high and low adolescent ethanol drinking, ADHI and ADLO lines, respectively) that significantly differ in ethanol drinking at adolescence. The S 0 generation and filial generations 1 (S 1 ), S 2 , and S 3 of ADHI and ADLO offspring were tested for basal or stress-induced ethanol intake at adulthood, or for shelter-seeking and risk-taking in the multivariate concentric square field test (MSCF). The study generated lines with significant differences in free-choice ethanol drinking at adolescence. The effects of the selection were observed at adulthood, beyond the stage in which the selection was conducted: S 1 -ADHI but not S 1 -ADLO adult male rats exhibited stress-induced drinking. These effects were associated with significant alterations in shelter-seeking and risk-taking behaviors. ADHI rats spent significantly less time in areas of the MSCF whose exploration entails risk-taking and significantly more time in dark, sheltered areas. Some of these effects were normalized by the administration of 0.5 g/kg ethanol. There were no line differences in ethanol-induced latency to lose the righting reflex or sleep time. These findings indicate that genetic risk of enhanced ethanol intake at adolescence is still present at adulthood, long after the developmental window when the selective breeding occurred. Exposure to stress at adulthood triggers the vulnerability associated with this genetic risk, an effect associated with enhanced anxiety., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Alcohol exposure and stressful events in life can induce long-lasting changes in physiology, behavior and gene expression patterns, eventually facilitating the development of psychiatric diseases like alcohol use disorders (AUD). Epigenetic mechanisms have been recently proposed to play a role in the cellular actions of alcohol via chromatin remodeling. Here we discuss interactions between stress and the pharmacological effects of alcohol, including the possibility that early exposure to, or withdrawal of, alcohol might induce stressful effects of their own. A specific aim is to describe novel molecular mechanisms by which stress, alcohol or their combined presentation impact on the epigenome. A key question is why only a fraction of the population progresses from regular, non-problematic, alcohol use to AUD, despite suffering from similar alcohol exposure. It is important to analyze how environmental factors, most notably stress, interact with the epigenetic machinery to increase vulnerability for AUD. The knowledge derived from this endeavor will be critical for the development of preventive strategies and new, drug- or gene-based, therapies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Restraint stress (RS) induces neurotoxicity in the hippocampus, yet most of the studies have employed protracted RS (i.e., ≈ 21 days). Binge ethanol can induce brain toxicity, an effect affected by age. It could be postulated that RS may facilitate ethanol-induced neurotoxicity, perhaps to a greater extent in adolescent vs. older subjects. We analyzed whether adolescent, adult or middle-aged male rats exposed to five episodes of RS followed, 72h later, by binge ethanol (i.e., two administrations of 2.5 g/kg ethanol) exhibited hippocampal neurotoxicity. Adolescents, but not adult or middle-aged rats, exhibited sensitivity to the neurotoxic effects of ethanol at dorsal CA2, ventral CA3 and ventral DG, and a neurotoxic effect of stress at dorsal CA1. Moreover, the combination of ethanol and stress exerted a synergistic effect upon cell degeneration at ventral CA1 and CA2, which was restricted to adolescents. Ethanol also increased cell degeneration, irrespective of age or stress, in dorsal CA3 and in dorsal DG; and ethanol and stress had, across all ages, a synergistic effect upon cell degeneration at the dorsal CA1. The greater neurotoxic response of adolescents to ethanol, stress, or ethanol+stress can put them at risk for the development of alcohol problems., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Rodent species are common in livestock production systems, and some of them are considered serious pests because of the sanitary problems and economic losses they cause. Information about microhabitat selection by rodent species in livestock production systems is necessary for understanding rodent requirements and to contribute to effective prevention and development of control measures for pest rodent species. In this work we study microhabitat selection by rodent species that inhabit pig and dairy farms in central Argentina. Rodent trapping was conducted over three years (2008-2011) on 18 livestock farms, each one sampled seasonally during one year. To study habitat selection, microhabitat characterizations were performed describing 22 environmental variables in captured sites and random trap sites without captures., Results: With a trapping effort of 7333 Sherman and 7026 cage live trap-nights, 444 rodents of seven species were captured (including the murine pest species Rattus norvegicus, R. rattus and Mus musculus and four native species). The three murines selected characteristics related to building structure and/or to food sources availability/proximity, while Akodon azarae selected sites with tall herbatious vegetation., Conclusions: We identified microhabitat characteristics that explain habitat distribution of small rodent species in these complex farm systems. This study contributes to broaden the integrated pest management of rodent pest species and could also contribute to the reduction of the use of rodenticides in these systems. © 2018 Society of Chemical Industry., (© 2018 Society of Chemical Industry.)

In order to describe the clinical and epidemiological characteristics of paracoccidioidomycosis, a descriptive study of all the cases diagnosed by the Clinical Microbiology Service at Dr. Julio C. Perrando hospital in the city of Resistencia (Chaco Province, Argentina) was conducted. Between 2011 and 2014, 46 cases were detected. In the period 2013-2014, an almost 4-fold increase in the incidence rate was detected. The chronic form of the disease was predominant with an average age of 53 years. Serological tests in 39 out of 46 patients were performed. In 15 of 39 patients, serological tests were the only diagnostic tool while in 4 patients with a microbiological diagnosis serological tests were non-reactive. In patients from endemic areas with non-specific infectious syndrome it is important to include paracoccidioidomycosis in the differential diagnosis and to apply all available diagnostic tools to reach a timely diagnosis and to reduce the long-term sequelae and their socio-economic impact., (Copyright © 2018 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Prenatal and/or early postnatal ethanol exposure (PEE) is associated with significant behavioral and physiological deficits in offspring, including alterations in stress response systems and a greater likelihood of alcohol use disorders. Stress-induced ethanol drinking after PEE, however, has been largely unexplored. The present study analyzed ethanol intake in male Sprague-Dawley rats after protracted prenatal and early postnatal ethanol exposure and tested whether social isolation during the sensitive period of adolescence modulates the effects of PEE on ethanol drinking. The dams were given 10% ethanol (or its vehicle) as the sole drinking fluid from gestational day 0 (GD0) to postnatal day 7 (PD7). On PD21, male offspring were housed individually (isolated housing group) or in pairs in standard cages (standard housing group). From PD56 to PD84, these male rats were tested for ethanol intake in 24-h, intermittent two-bottle choice sessions that were conducted across 4 weeks. Maternal ethanol consumption during gestation and during the first week of life of the offspring averaged 6.10-8.20 g/kg/22 h. Isolation housing during adolescence increased free-choice ethanol drinking in young adulthood. The main novel finding was that this facilitative effect of isolation on absolute and percent ethanol intake was significantly greater in PEE rats than in control counterparts not exposed to the prenatal and early postnatal ethanol exposure (effect sizes [η 2 p]: 0.24-0.32). The present results suggest that PEE renders the individual sensitive to the facilitative effect of stress exposure on ethanol intake., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A Late Cretaceous-aged multi-taxon nesting site from Romania preserved in three dimensions reveals the earliest example of nest site sharing yet known from the vertebrate fossil record. Eggshell and osteological evidence combined in this single accumulation demonstrate that at least four vertebrate taxa including enantiornithine birds and another avian of indeterminate affinities as well as crocodylomorphs and gekkotan squamates nested together in the same place. Colonial nesting in enantiornithines was previously described from this site; here, we present the first fossil evidence that other vertebrates also nested in the same place, perhaps exploiting the presence of the large bird colony. We describe four distinct eggshell morphotypes that have been collected from this site and draw palaeoecological inferences based on this unique multi-taxon nesting association.

Adolescents exhibit, when compared to adults, altered responsivity to the unconditional effects of ethanol. It is unclear if this has a role in the excessive ethanol intake of adolescents. Wistar rats from the third filial generation (F 3 ) of a short-term breeding program which were selected for high (STDRHI) vs. low (STDRLO) ethanol intake during adolescence, were assessed for ethanol-induced (0.0, 1.25 or 2.5 g/kg) Fos immunoreactivity (Fos-ir) in the central (Ce), basolateral (BLA) and medial (Me) amygdaloid nuclei; nucleus accumbens core and shell (AcbC, AcbSh), ventral tegmental area (VTA), as well as prelimbic and infralimbic (PrL, IL) prefrontal cortices. Following i.p. administration of saline, and across the structures measured, Fos-ir was significantly greater in STDRHI than in STDRLO rats. Across both lines, baseline Fos-ir was significantly lower in BLA than in any other structure, whereas PrL, IL and Shell did not differ between each other and exhibited significantly greater level of baseline neural activation than Ce, Me, AcbC and VTA. STDRLO, but not STDRHI, rats exhibited ethanol-induced Fos-ir in Ce. STRDHI, but not STDRLO, rats exhibited an ethanol-induced Fos-ir depression in AcbC. Key maternal care behaviors (i.e., grooming of the pups, latency to retrieve the pups, time spent in the nest and time adopting a kiphotic posture) were fairly similar across lines. There were significant intergenerational variations in the amount self-licking behaviors in STDRHI dams as well as an increased amount of exploration of the cage in these animals, when compared to STDRLO counterparts. These results indicate that short term selection for differential alcohol intake during adolescence yields heightened neural activity at baseline (i.e., after vehicle) in STRDHI vs. STDRLO adolescent rats, and differential sensitivity to ethanol-induced Fos immunoreactivity in Ce and in AcbC. It is unlikely that rearing patterns explained the neural differences reported, between STDRHI and STDRLO rats., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Thalattosuchians are a group of Mesozoic crocodylomorphs known from aquatic deposits of the Early Jurassic-Early Cretaceous that comprises two main lineages of almost exclusively marine forms, Teleosauridae and Metriorhynchoidea. Teleosaurids were found in shallow marine, brackish and freshwater deposits, and have been characterized as semiaquatic near-shore forms, whereas metriorhynchids are a lineage of fully pelagic forms, supported by a large set of morphological characters of the skull and postcranial anatomy. Recent contributions on Thalattosuchia have been focused on the study of the endocranial anatomy. This newly available information provides novel evidence to suggest adaptations on the neuroanatomy, senses organs, vasculature, and behavioral evolution of these crocodylomorphs. However, is still not clear if the major morphological differences between teleosaurids and metriorhynchids were also mirrored by changes in the braincase and endocranial anatomy. Based on X-ray CT scanning and digital endocast reconstructions we describe the braincase and endocranial anatomy of two well-preserved specimens of Thalattosuchia, the semiaquatic teleosaurid Steneosaurus bollensis and the pelagic metriorhynchid Cricosaurus araucanensis . We propose that some morphological traits, such as: an enlarged foramen for the internal carotid artery, a carotid foramen ventral to the occipital condyle, a single CN XII foramen, absence of brain flexures, well-developed cephalic vascular system, lack of subtympanic foramina and the reduction of the paratympanic sinus system, are distinctive features of Thalattosuchia. It has been previously suggested that the enlarged foramen for the internal carotid artery, the absence of brain flexures, and the hypertrophied cephalic vascular system were synapomorphies of Metriorhynchidae; however, new information revealed that all of these features were already established at the base of Thalattosuchia and might have been exapted later on their evolutionary history. Also, we recognized some differences within Thalattosuchia that previously have not been received attention or even were overlooked (e.g., circular/bilobate trigeminal foramen, single/double CN XII foramen, separation of the cranioquadrate canal from the external otic aperture, absence/presence of lateral pharyngeal foramen). The functional significances of these traits are still unclear. Extending the sampling to other Thalattosuchia will help to test the timing of acquisition and distribution of these morphological modifications among the whole lineage. Also comparison with extant marine tetrapods (including physiological information) will be crucial to understand if some (and/or which) of the morphological peculiarities of thalattosuchian braincases are products of directional natural selection resulting in a fully adaptation to a nektonic life style., Competing Interests: The authors declare that they have no competing interests.

Purpose: The purpose of our study was to evaluate effective ischemia and its associated complications using the limb occlusion pressure technique versus standard pneumatic ischemia technique., Design: Single-centered randomized, controlled clinical trial., Methods: One hundred sixty participants were randomized into two equal and parallel groups: (1) intervention group-LOP technique, and (2) control group-standard pneumatic ischemia technique., Findings: Anesthetic incidences (need to administer analgesics for pain and/or hypnotics for anxiety) were similar in both groups. Statistically significant differences were observed for pain, hyperemia, and hospitalization, with higher values in the control group. Patients in the intervention group had, at 95% confidence, a 2.9 times greater chance of having optimal ischemia (assessed as 9 on the analog scale) than patients in the control group (odds ratio, 2.9; 95% confidence interval, 1.4 to 6.1)., Conclusions: Intervention group patients had lower indexes of hyperemia, pain, and hospital stay., (Copyright © 2017 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

The aim of this work was to study the distribution of Phlebotominae (Diptera: Psycodidade) abundance in time and space in an area in northeastern Argentina with vector transmission of visceral and tegumentary leishmaniasis. For this, 51 households were selected using a 'worst scenario' criterion where one light trap was set during two consecutive nights in peridomiciles in the transitions between the four seasons, and the environment was surveyed simultaneously. The relationships of phlebotomine assemblage structure and the most abundant species with seasonality and environmental variables were evaluated using a canonical correspondence analysis and generalized linear mixed models, respectively. A total of 5110 individuals were captured. Lutzomyia longipalpis (Lutz & Neiva, 1912) and Nyssomyia whitmani (Antunes & Coutinho, 1939) were the most abundant species captured in all samplings (98.3% of the total capture). The period of highest abundance of Lu. longipalpis was early autumn, and it was distributed in the most urbanized areas. Nyssomyia whitmani occupied mainly the less urbanized areas, showing peaks of abundance in early spring and summer. Other species were captured in low numbers and showed seasonal-spatial variations similar to those of Ny. whitmani. We confirmed Leishmania spp. vector persistence throughout the year in spatial patches of high abundance even during the less favorable season., (© 2017 The Royal Entomological Society.)

Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei . The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set ( n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis . According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions: Aspergillus terreus was most prevalent, followed by A. citrinoterreus . Posaconazole was the most potent drug against A. terreus , but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.