Nontoxic effects of thymol, carvacrol, cinnamaldehyde, and garlic oil on dung beetles: A potential alternative to ecotoxic anthelmintics.

The sustainability of the traditional extensive livestock sector will only be possible if healthy dung-decomposing insect communities are preserved. However, many current pharmaceutical anthelmintics are harmful to dung beetles, their presence can have a negative impact on biological systems. Phytochemical anthelmintics are an alternative to ecotoxic synthetic pharmaceutical anthelmintics, although ecotoxicological tests of their possible indirect effects on dung beetles are required to demonstrate their viability. In this study, the potential ecotoxicity of thymol, carvacrol, cinnamaldehyde and garlic oil (diallyl disulfide and diallyl trisulfide) were tested for the first time. Inhibition of antennal response was measured as a relevant parameter by obtaining relevant toxicity thresholds derived from concentration‒response curves, such as the IC50. All phytochemical compounds tested were demonstrated to be suitable alternative candidates to the highly ecotoxic compound ivermectin, considering their non-toxicity to nontarget organisms. Residues of the phytochemical antiparasitics found in cattle droppings were extremely low, even undetectable in the case of diallyl disulfide and diallyl trisulfide. Furthermore, our results showed that none of the phytochemical compounds have ecotoxic effects, even at extremely high concentrations, including those almost 1000 times higher than what is most likely to be found in dung susceptible to ingestion by dung beetles in the field. We can conclude that the four selected phytochemical compounds meet the requirements to be considered reliable alternatives to ecotoxic veterinary medicinal products, such as ivermectin.

Links Between Feeding Preferences and Electroantennogram Response Profiles in Dung Beetles: The Importance of Dung Odor Bouquets.

The detection of dung odors is a crucial step in the food-searching behavior of dung beetles (Coleoptera: Scarabaeoidea). Yet, whether certain compounds characteristic of a given dung type contribute to a 'choosy generalism' behavior proposed for this taxonomic group is unknown. To address this, we analyzed the chemical composition of three types of dung (cow, horse, and rabbit) and conducted behavioral and electroantennogram (EAG) bioassays on 15 species of dung beetles using 19 volatile organic compounds representing the three dung samples. Chemical analyses revealed substantial qualitative and quantitative differences among dung types. When offered these food options in an olfactometer, 14 species exhibited a feeding preference. Surprisingly, all 19 compounds used in the EAG assays elicited antennal responses, with species displaying different olfactory profiles. The relationship between behavioral preferences and electrophysiological profiles highlighted that species with different food preferences had differences in antennal responses. Moreover, a specific set of EAG-active compounds (nonanal, sabinene, acetophenone, ρ-cresol, 2-heptanone, 1H-indole, and 6-methyl-5-hepten-2-one) were the strongest drivers in the distinct sensory profiles of the trophic preference groups. Our results point to the importance of the whole bouquet of dung-emanating compounds in driving food-searching behavior, but specific volatiles could aid in determining highly marked trophic preferences in certain species.

Early radiological worsening of SARS-CoV-2 pneumonia predicts the need for ventilatory support.

OBJECTIVES: Identifying early markers of poor prognosis of coronavirus disease 2019 (COVID-19) is mandatory. Our purpose is to analyze by chest radiography if rapid worsening of COVID-19 pneumonia in the initial days has predictive value for ventilatory support (VS) need. METHODS: Ambispective observational ethically approved study in COVID-19 pneumonia inpatients, validated in a second outpatient sample. Brixia score (BS) was applied to the first and second chest radiography required for suspected COVID-19 pneumonia to determine the predictive capacity of BS worsening for VS need. Intraclass correlation coefficient (ICC) was previously analyzed among three radiologists. Sensitivity, specificity, likelihood ratios, AUC, and odds ratio were calculated using ROC curves and binary logistic regression analysis. A value of p < .05 was considered statistically significant. RESULTS: A total of 120 inpatients (55 ± 14 years, 68 men) and 112 outpatients (56 ± 13 years, 61 men) were recruited. The average ICC of the BS was between 0.812 (95% confidence interval 0.745-0.878) and 0.906 (95% confidence interval 0.844-0.940). According to the multivariate analysis, a BS worsening per day > 1.3 points within 10 days of the onset of symptoms doubles the risk for requiring VS in inpatients and 5 times in outpatients (p < .001). The findings from the second chest radiography were always better predictors of VS requirement than those from the first one. CONCLUSION: The early radiological worsening of SARS-CoV-2 pneumonia after symptoms onset is a determining factor of the final prognosis. In elderly patients with some comorbidity and pneumonia, a 48-72-h follow-up radiograph is recommended. KEY POINTS: • An early worsening on chest X-ray in patients with SARS-CoV-2 pneumonia is highly predictive of the need for ventilatory support. • This radiological worsening rate can be easily assessed by comparing the first and the second chest X-ray. • In elderly patients with some comorbidity and SARS-CoV-2 pneumonia, close early radiological follow-up is recommended.

First observation on the predation of a non-arthropod species by a dung beetle species: The case of Canthon chalybaeus and the snail Bulimulus apodemetes.

We described, for the first time, a case of predation of a non-arthropod species by a dung beetle species. Canthon chalybaeus Blanchard, 1843 kills healthy individuals of the terrestrial snail Bulimulus apodemetes (D'Orbigny, 1835) showing an evident pattern of physical aggressiveness in the attacks using the dentate clypeus and the anterior tibiae. The description of this predatory behaviour was complemented with the analysis of the chemical secretions of the pygidial glands of C. chalybaeus, highlighting those main chemical compounds that, due to their potential toxicity, could contribute to death of the snail. We observed a high frequency of predatory interactions reinforcing the idea that predation in dung beetles is not accidental and although it is opportunistic it involves a series of behavioural sophistications that suggest an evolutionary pattern within Deltochilini that should not only be better studied from a behavioural point of view but also phylogenetically.

Dung Beetle Assemblages Attracted to Cow and Horse Dung: The Importance of Mouthpart Traits, Body Size, and Nesting Behavior in the Community Assembly Process.

Dung beetles use excrement for feeding and reproductive purposes. Although they use a range of dung types, there have been several reports of dung beetles showing a preference for certain feces. However, exactly what determines dung preference in dung beetles remains controversial. In the present study, we investigated differences in dung beetle communities attracted to horse or cow dung from a functional diversity standpoint. Specifically, by examining 18 functional traits, we sought to understand if the dung beetle assembly process is mediated by particular traits in different dung types. Species specific dung preferences were recorded for eight species, two of which prefer horse dung and six of which prefer cow dung. Significant differences were found between the functional traits of the mouthparts of the dung beetles attracted to horse dung and those that were attracted to cow dung. Specifically, zygum development and the percentage of the molar area and the conjunctive area differed between horse and cow dung colonizing beetles. We propose that the quantitative differences in the mouthpart traits of the species attracted to horse and cow dung respectively could be related to the differential capacity of the beetles to filtrate and concentrate small particles from the dung. Hence, the dung preference of dung beetles could be related to their ability to exploit a specific dung type, which varies according to their mouthpart traits. Moreover, we found that larger and nester beetles preferred cow dung, whereas smaller and non-nester beetles preferred horse dung. This finding could be related to the tradeoff between fitness and parental investments, and to the suitability of the trophic resource according to the season and species phenology.

Onthophagus pilauco sp. nov. (Coleoptera, Scarabaeidae): evidence of beetle extinction in the Pleistocene-Holocene transition in Chilean Northern Patagonia.

The South American Pleistocene-Holocene transition has been characterized by drastic climatic and diversity changes. These rapid changes induced one of the largest and most recent extinctions in the megafauna at the continental scale. However, examples of the extinction of small animals (e.g., insects) are scarce, and the underlying causes of the extinction have been little studied. In this work, a new extinct dung beetle species is described from a late Pleistocene sequence (~15.2 k cal yr BP) at the paleoarcheological site Pilauco, Chilean Northern Patagonia. Based on morphological characters, this fossil is considered to belong to the genus Onthophagus Latreille, 1802 and named Onthophagus pilauco sp. nov. We carried out a comprehensive revision of related groups, and we analyzed the possible mechanism of diversification and extinction of this new species. We hypothesize that Onthophagus pilauco sp. nov. diversified as a member of the osculatii species-complex following migration processes related to the Great American Biotic Interchange (~3 Ma). The extinction of O. pilauco sp. nov. may be related to massive defaunation and climatic changes recorded in the Plesitocene-Holocene transition (12.8 k cal yr BP). This finding is the first record of this genus in Chile, and provides new evidence to support the collateral-extinction hypothesis related to the defaunation.

Prognostic value of thrombin generation parameters in hospitalized COVID-19 patients.

SARS-CoV-2 infection increases the risk of thrombosis by different mechanisms not fully characterized. Although still debated, an increase in D-dimer has been proposed as a first-line hemostasis test associated with thromboembolic risk and unfavorable prognosis. We aim to systematically and comprehensively evaluate the association between thrombin generation parameters and the inflammatory and hypercoagulable state, as well as their prognostic value in COVID-19 patients. A total of 127 hospitalized patients with confirmed COVID-19, 24 hospitalized patients with SARS-CoV-2-negative pneumonia and 12 healthy subjects were included. Clinical characteristics, thrombin generation triggered by tissue factor with and without soluble thrombomodulin, and also by silica, as well as other biochemical parameters were assessed. Despite the frequent use of heparin, COVID-19 patients had similar thrombin generation to healthy controls. In COVID-19 patients, the thrombin generation lag-time positively correlated with markers of cell lysis (LDH), inflammation (CRP, IL-6) and coagulation (D-dimer), while the endogenous thrombin potential (ETP) inversely correlated with D-dimer and LDH, and positively correlated with fibrinogen levels. Patients with more prolonged lag-time and decreased ETP had higher peak ISTH-DIC scores, and had more severe disease (vascular events and death). The ROC curve and Kaplan Meier estimate indicated that the D-dimer/ETP ratio was associated with in-hospital mortality (HR 2.5; p = 0.006), and with the occurrence of major adverse events (composite end-point of vascular events and death) (HR 2.38; p = 0.004). The thrombin generation ETP and lag-time variables correlate with thromboinflammatory markers, and the D-dimer/ETP ratio can predict major adverse events in COVID-19.

Validity of Chronic Venous Disease Diagnoses and Epidemiology Using Validated Electronic Health Records From Primary Care: A Real-World Data Analysis.

PURPOSE: The aim of this study was to evaluate the validity of lower limb chronic venous disease (CVD) diagnoses entered in a large electronic health record database in primary care in Catalonia, Spain; to investigate the reliability of these data for research purposes; and to estimate the prevalence and incidence of CVD, chronic venous insufficiency (CVI), and venous leg ulcer (VLU). DESIGN: Real-world data analysis based on a large electronic health record database in primary care in Catalonia, Spain. METHODS: We used a primary care research database (Information System for the Development of Research in Primary Care [SIDIAP]), which contains anonymous data on some 5.8 million people from 279 primary care centers, accounting for more than 80% of the Catalonian population and 15% of the Spanish population. We evaluated the validity of the ICD-10 codes for CVD in SIDIAP for 200 adult patients through the responses of 20 primary care physicians to a questionnaire. FINDINGS: The positive predictive value of CVD in SIDIAP was 89.95% (95% confidence interval [CI] 84.99-93.40). The prevalence rates for CVD, CVI, and VLU were 9.54% (95% CI 9.51-9.56), 3.87%, and 0.33%, respectively. The incidence rates for CVD, CVI, and VLU were 7.91/1,000 person-years (95% CI 7.82-8.00), 3.37/1,000 person-years (95% CI 3.31-3.43), and 0.23/1,000 person-years (95% CI 0.21-0.24), respectively. CONCLUSIONS: The Catalonian SIDIAP database contains valid CVD diagnoses. The prevalence and incidence rates found using real-world data are low compared with those in the literature, possibly because CVD is an underdiagnosed entity. CLINICAL RELEVANCE: Real-world data can inform clinicians on lower limb venous health in a population, show changes as individuals age, and reveal aspects where healthcare can be improved.

Planar, strong magnetic field source for a chip ion trap.

We present a planar, scalable magnetic field source, originally conceived for a chip ion trap. It consists of two symmetric sections, each with several independent currents arranged in coplanar, concentric rectangular loops. The currents allow for tuning the strength of the field and its lowest-order derivatives at one discretional position along the source's vertical symmetry axis, a few mm above its surface. We describe the construction and calibration of the device and the cryogenic setup. The two most important current configurations for a Penning ion trap, the homogeneous field and the magnetic bottle, are investigated experimentally. Homogeneous fields around 0.5 T are routinely reached. We discuss the maximum attainable field, and we briefly describe ongoing further developments aiming at homogeneous fields well above 1 T.

Thermal niche helps to explain the ability of dung beetles to exploit disturbed habitats.

In terrestrial ecosystems, insects face a wide range of temperatures among habitats and time; consequently, the thermal niche is one of the main determinants of habitat selection and temporal patterns of activity. The replacement of native forests changes micro-climatic conditions and reduces the diversity of dung beetles; however, the physiological mechanisms behind these changes are not clear. We explore the role of the thermal niche in dung beetles to explain the ability of native species to exploit human-created habitats. Using infrared thermography, we measured variables associated with the thermal niche in 17 native species and used linear mixed-effects model and ANOVAs to compare disturbed habitats and the native forest. Endothermy and body mass explained the ability of dung beetles to exploit human-created open habitats. Small and diurnal species with very low endothermy were able to exploit deforested open habitats; evening/nocturnal/crepuscular species showed similar body mass and high endothermy in all habitats. Regarding thermoregulation mechanisms, none of the species (except one) showed defined or efficient mechanisms of physiological thermoregulation. In view of the accelerated process of forest replacement and climate change, a more profound understanding of the physiological requirements of species is essential to predict and mitigate future extinctions.

Lung Ultrasound for Heart Failure Diagnosis in Primary Care.

BACKGROUND: Lung ultrasound (LUS) is useful for diagnosing pulmonary congestion, but its value in primary care remains unclear. We investigated whether LUS improved diagnostic accuracy in outpatients with heart failure (HF) suspicion. METHODS AND RESULTS: LUS was performed on 2 anterior (A), 2 lateral (L), and 2 posterior (P) areas per hemithorax. An area was positive when ≥3 B-lines were observed. Two diagnostic criteria were used: for LUS-C1, 2 positive areas of 4 (A-L) on each hemithorax; and for LUS-C2, 2 positive areas of 6 (A-L-P) on each hemithorax. A cardiologist blinded to LUS validated HF diagnosis. 162 patients were included (age 75.6 ± 9.4 years, 70.4% women). Both LUS criteria, alone and combined with other HF diagnostic criteria, were accurate for identifying HF. LUS-C2 outperformed LUS-C1, showing remarkable specificity (0.99) and positive predictive value (0.92). LUS-C2, together with Framingham criteria, N-terminal pro-B-type natriuretic peptide, and electrocardiogram, added diagnostic value (area under the receiver operating characteristic curves 0.90 with LUS-C2 vs 0.84 without; P = .006). In the absence of N-terminal pro-B-type natriuretic peptide, LUS-C2 significantly reclassified one-third of patients above Framingham criteria and electrocardiogram (net reclassification improvement 0.65, 95% confidence interval 0.04-1.1). CONCLUSIONS: LUS was accurate enough to rule-in HF in a primary care setting. The accuracy of diagnostic workup for HF in primary care is enhanced by incorporating LUS, irrespective NT-proBNP availability.

Biomagnification and body distribution of ivermectin in dung beetles.

A terrestrial test system to investigate the biomagnification potential and tissue-specific distribution of ivermectin, a widely used parasiticide, in the non-target dung beetle Thorectes lusitanicus (Jekel) was developed and validated. Biomagnification kinetics of ivermectin in T. lusitanicus was investigated by following uptake, elimination, and distribution of the compound in dung beetles feeding on contaminated faeces. Results showed that ivermectin was biomagnified in adults of T. lusitanicus when exposed to non-lethal doses via food uptake. Ivermectin was quickly transferred from the gut to the haemolymph, generating a biomagnification factor (BMFk) three times higher in the haemolymph than in the gut after an uptake period of 12 days. The fat body appeared to exert a major role on the biomagnification of ivermectin in the insect body, showing a BMFk 1.6 times higher than in the haemolymph. The results of this study highlight that the biomagnification of ivermectin should be investigated from a global dung-based food web perspective and that the use of these antiparasitic substances should be monitored and controlled on a precautionary basis. Thus, we suggest that an additional effort be made in the development of standardised regulatory recommendations to guide biomagnification studies in terrestrial organisms, but also that it is necessary to adapt existing methods to assess the effects of such veterinary medical products.

Impact of telemedicine on the clinical outcomes and healthcare costs of patients with chronic heart failure and mid-range or preserved ejection fraction managed in a multidisciplinary chronic heart failure programme: A sub-analysis of the iCOR randomized trial.

Background: The efficacy of telemedicine in the management of patients with chronic heart failure and left ventricular ejection fraction ≥40% is poorly understood. The aim of our analysis was to evaluate the efficacy of a telemedicine-based intervention specifically in these patients, as compared to standard of care alone. Methods: The Insuficiència Cardiaca Optimització Remota (iCOR) study was a single centre, randomised, controlled trial, designed to evaluate a telemedicine intervention added to an existing hospital/primary care multidisciplinary, integrated programme for chronic heart failure patients. 178 participants were randomised to telemedicine or usual care, and were followed for six months. For the present sub-analysis, only iCOR participants (n = 116) with left ventricular ejection fraction ≥40% were included. The primary study endpoint was the incidence of an acute non-fatal heart failure event, defined as a new episode of worsening of symptoms and signs consistent with acute heart failure requiring intravenous diuretic therapy. The healthcare-related costs in each study group were also evaluated. Results: The incidence of the first occurrence of the primary endpoint was significantly lower in the telemedicine arm (22% vs 56%, p<0.001), with a hazard ratio of 0.33 comparing to the usual care arm (95% confidence interval 0.17­0.64). Telemedicine was also associated with lower mean overall chronic heart failure care-related costs compared to usual care (8163€ vs 4993€, p=0.001). The results were consistent in both left ventricular ejection fraction of 40­49% and left ventricular ejection fraction ≥50% patients. Conclusions: Our results suggest that telemedicine is a promising strategy for the management of chronic heart failure patients with left ventricular ejection fraction ≥40%. These findings should be replicated in larger cohorts.

Thermoregulatory syndromes of two sympatric dung beetles with low energy costs.

In heterotherm insects, endothermy implies a high energy cost due to the generation and regulation of body temperature during different activities such as flight, food location, fighting and even walking. We studied the thermoregulation process and the cost of the thermoregulation strategies in two sympatric dung beetles, Sulcophanaeus batesi and S. imperator under heat and cold stress conditions. We used a set of physiological variables to exemplify the capacity of thermolimit respirometry combined with infrared thermography to derive relevant variables capable of describing different thermoregulation syndromes. Habitat use and thermal niche differed notably between S. batesi and S. imperator, reflecting their contrasted thermal requirements. In S. imperator, thermal specialization for high temperatures was observed, being active mainly during the warmer period of the day. On the other hand, thermal adaptation in S. batesi allows its preference for cold exhibiting a morning activity periods, avoiding higher temperatures. The thermophilic strategy used by Sulcophanaeus imperator minimized the energy expenditure produced during the cooling of the body by respiration without thereby endangering higher thermal limits. In this case, S. batesi, the species with a preference for the coldest environments, presented the lowest thermal limits, although the energy cost needed to stay active during cooling was significantly lower than that in S. imperator. Sulcophanaeus imperator and S. batesi showed evident 'economizing' strategies associated with hot and cold environmental conditions, respectively. In contrast, if both species experience a deviation from their thermal optimum, a decrement in their performance could be produced.

What do healthcare professionals need to turn risk models for type 2 diabetes into usable computerized clinical decision support systems? Lessons learned from the MOSAIC project.

BACKGROUND: To understand user needs, system requirements and organizational conditions towards successful design and adoption of Clinical Decision Support Systems for Type 2 Diabetes (T2D) care built on top of computerized risk models. METHODS: The holistic and evidence-based CEHRES Roadmap, used to create eHealth solutions through participatory development approach, persuasive design techniques and business modelling, was adopted in the MOSAIC project to define the sequence of multidisciplinary methods organized in three phases, user needs, implementation and evaluation. The research was qualitative, the total number of participants was ninety, about five-seventeen involved in each round of experiment. RESULTS: Prediction models for the onset of T2D are built on clinical studies, while for T2D care are derived from healthcare registries. Accordingly, two set of DSSs were defined: the first, T2D Screening, introduces a novel routine; in the second case, T2D Care, DSSs can support managers at population level, and daily practitioners at individual level. In the user needs phase, T2D Screening and solution T2D Care at population level share similar priorities, as both deal with risk-stratification. End-users of T2D Screening and solution T2D Care at individual level prioritize easiness of use and satisfaction, while managers prefer the tools to be available every time and everywhere. In the implementation phase, three Use Cases were defined for T2D Screening, adapting the tool to different settings and granularity of information. Two Use Cases were defined around solutions T2D Care at population and T2D Care at individual, to be used in primary or secondary care. Suitable filtering options were equipped with "attractive" visual analytics to focus the attention of end-users on specific parameters and events. In the evaluation phase, good levels of user experience versus bad level of usability suggest that end-users of T2D Screening perceived the potential, but they are worried about complexity. Usability and user experience were above acceptable thresholds for T2D Care at population and T2D Care at individual. CONCLUSIONS: By using a holistic approach, we have been able to understand user needs, behaviours and interactions and give new insights in the definition of effective Decision Support Systems to deal with the complexity of T2D care.

Author Correction: First assessment of the comparative toxicity of ivermectin and moxidectin in adult dung beetles: Sub-lethal symptoms and pre-lethal consequences.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

The prognostic value of blood pressure control delay in newly diagnosed hypertensive patients.

OBJECTIVE: Various studies have suggested that a delay in the time between diagnosing hypertension and its correct control (D-C, diagnostic-control time) is linked to a worse prognosis. The aim of this study was to examine the relationship between D-C time and all-cause mortality, or the incidence of cardiovascular events, in patients more than 60 years newly diagnosed with hypertension. METHODS: This is a longitudinal, retrospective, population study employing data gathered from the electronic medical records of patients recently diagnosed with hypertension in 45 primary healthcare centres located in Barcelona (Catalonia). A multivariable logistic regression and Cox regression models were constructed. Goodness-of-fit was assessed through the Hosmer & Lemeshow test. RESULTS: A total of 18 721 newly diagnosed hypertensive patients were included between 2007 and 2012. The follow-up lasted until October 2015, or the appearance of a cardiovascular event or death because of any cause. The median D-C time was 49 days and its distribution by tertiles was the following: 29 days or less, 30-124 days, and at least 125 days. Higher hypertensive status, obesity, diabetes mellitus, and male sex were independently associated with longer D-C time (≥125 days). At 5.4 years follow-up, patients with longer D-C times presented statistically significant greater incidence of all-cause mortality. CONCLUSION: A delay in blood pressure control is significantly associated with an increase in the rate of all-cause mortality.

First assessment of the comparative toxicity of ivermectin and moxidectin in adult dung beetles: Sub-lethal symptoms and pre-lethal consequences.

Among macrocyclic lactones (ML), ivermectin (IVM) and moxidectin (MOX) potentially affect all Ecdysozoan species, with dung beetles being particularly sensitive. The comparative effects of IVM and MOX on adult dung beetles were assessed for the first time to determine both the physiological sub-lethal symptoms and pre-lethal consequences. Inhibition of antennal response and ataxia were tested as two intuitive and ecologically relevant parameters by obtaining the lowest observed effect concentration (LOEC) values and interpolating other relevant toxicity thresholds derived from concentration-response curves (IC50, as the concentration of each ML where the antennal response is inhibited by half; and pLC50, as the quantity of ingested ML where partial paralysis was observed by half of treated individuals) from concentration-response curves. Both sub-lethal and pre-lethal symptoms obtained in this study coincided in that IVM was six times more toxic than MOX for adult dung beetles. Values of LOEC, IC50 and pLC50 obtained for IVM and MOX evaluated in an environmental context indicate that MOX, despite needing more time for tis elimination in the faeces, would be twice as harmful to dung beetles as IVM. This approach will be valuable to clarify the real impact of MLs on dung beetle health and to avoid the subsequent environmental consequences.