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Multi-species mutualistic interactions are ubiquitous and essential in nature, yet they face several threats, many of which have been exacerbated in the Anthropocene era. Understanding the factors that drive the stability and persistence of mutualism has become increasingly important in light of global change. Although dispersal is widely recognized as a crucial spatially explicit process in maintaining biodiversity and community structure, knowledge about how the dispersal of mutualists contributes to the persistence of mutualistic systems remains limited. In this study, we used a synthetic mutualism formed by genetically modified budding yeast to investigate the effect of dispersal on the persistence and stability of mutualisms under exploitation. We found that dispersal increased the persistence of exploited mutualisms by 80% compared to the isolated systems. Furthermore, our results showed that dispersal increased local diversity, decreased beta diversity among local communities, and stabilized community structure at the regional scale. Our results indicate that dispersal can allow mutualisms to persist in meta-communities by reintroducing species that are locally competitively excluded by exploiters. With limited dispersal, e.g., due to increased fragmentation of meta-communities, mutualisms might be more prone to breakdown. Taken together, our results highlight the critical role of dispersal in facilitating the persistence of mutualism., (© The Author(s) [2025]. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

This work introduces the Queen's University Agent-Based Outbreak Outcome Model (QUABOOM). This tool is an agent-based Monte Carlo simulation for modelling epidemics and informing public health policy. We illustrate the use of the model by examining capacity restrictions during a lockdown. We find that public health measures should focus on the few locations where many people interact, such as grocery stores, rather than the many locations where few people interact, such as small businesses. We also discuss a case where the results of the simulation can be scaled to larger population sizes, thereby improving computational efficiency., (© 2024 The Authors.)

Bumblebees have been considered one of the most important pollinators on the planet. However, recent reports of bumblebee decline have raised concern about a significant threat to ecosystem stability. Infectious diseases caused by multiple pathogen infections have been increasingly recognized as an important mechanism behind this decline worldwide. Understanding the determining factors that influence the assembly and composition of pathogen communities among bumblebees can provide important implications for predicting infectious disease dynamics and making effective conservation policies. Here, we study the relative importance of biotic interactions versus interspecific host resistance in shaping the pathogen community composition of bumblebees in China. We first conducted a comprehensive survey of 13 pathogens from 22 bumblebee species across China. We then applied joint species distribution modeling to assess the determinants of pathogen community composition and examine the presence and strength of pathogen-pathogen associations. We found that host species explained most of the variations in pathogen occurrences and composition, suggesting that host specificity was the most important variable in predicting pathogen occurrences and community composition in bumblebees. Moreover, we detected both positive and negative associations among pathogens, indicating the role of competition and facilitation among pathogens in determining pathogen community assembly. Our research demonstrates the power of a pluralistic framework integrating field survey of bumblebee pathogens with community ecology frameworks to understand the underlying mechanisms of pathogen community assembly.

To avoid predation by visual predators, caterpillars can be cryptic to decrease detectability or aposematic to warn predators of potential unpalatability. However, for some species, it is not clear if conspicuous patches are selected to avoid predation. For example, Pandora sphinx ( Eumorpha pandorus , Lepidoptera: Sphingidae) caterpillars are assumed to be palatable and have both cryptic (green, brown) and conspicuous (orange, red) color morphs. Five lateral, off-white to yellow patches on either side may serve as a warning for predators or to draw attention away from the caterpillar's form to function as distractive marks. We conducted a field study in three temperate fragmented forests in Massachusetts to investigate the potential utility of E. pandorus coloration and conspicuous patches. Using four plasticine caterpillar prey model treatments, green and red with and without lateral conspicuous patches, we tested the effects of color, patch patterning, and seasonality on attack rates by a variety of taxa. We found that 43% of the prey models ( n  = 964) had bite marks by an array of predators including arthropods (67.5%), birds (18.2%), rodents (11.5%), and large mammals (2.8%). Arthropods as dominant predators align with conclusions from previous studies of prey models placed near ground level. Attack rates peaked for arthropods in late August and early September but were more constant across trials for vertebrates. Arthropods, a heterogeneous group, as indicated by the variety of bite marks, showed significantly higher attack rates on green colored prey models and a tendency of higher attack on solid (non-patch patterned) prey models. Vertebrates, more visually oriented predators, had significantly higher attack rates on red colored prey models and patch patterned prey models. Thus, our results did not suggest that conspicuous patch patterning reduced predation and therefore, we did not find support for the distractive mark hypothesis or warning hypothesis. Further, our study shows clear contrasting interpretations by different predators regarding visual defensive strategies., Competing Interests: We confirm that this work is original and has not been published elsewhere, nor is it currently under consideration for publication elsewhere. We declare no conflicts of interest., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Insect mutualisms are essential for reproduction of many plants, protection of plants and other insects, and provisioning of nutrients for insects. Disruption of these mutualisms by global change can have important implications for ecosystem processes. Here, we assess the general effects of global change on insect mutualisms, including the possible impacts on mutualistic networks. We find that the effects of global change on mutualisms are extremely variable, making broad patterns difficult to detect. We require studies focusing on changes in cost-benefit ratios, effects of partner dependency, and degree of specialization to further understand how global change will influence insect mutualism dynamics. We propose that rapid coevolution is one avenue by which mutualists can ameliorate the effects of global change., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Graphs/networks have become a powerful analytical approach for data modeling. Besides, with the advances in sensor technology, dynamic time-evolving data have become more common. In this context, one point of interest is a better understanding of the information flow within and between networks. Thus, we aim to infer Granger causality (G-causality) between networks' time series. In this case, the straightforward application of the well-established vector autoregressive model is not feasible. Consequently, we require a theoretical framework for modeling time-varying graphs. One possibility would be to consider a mathematical graph model with time-varying parameters (assumed to be random variables) that generates the network. Suppose we identify G-causality between the graph models' parameters. In that case, we could use it to define a G-causality between graphs. Here, we show that even if the model is unknown, the spectral radius is a reasonable estimate of some random graph model parameters. We illustrate our proposal's application to study the relationship between brain hemispheres of controls and children diagnosed with Autism Spectrum Disorder (ASD). We show that the G-causality intensity from the brain's right to the left hemisphere is different between ASD and controls.

Understanding how mutualisms persist over time requires investigations of how mutualist species coevolve and adapt to the interaction. In particular, the key factors in the evolution of mutualisms are the costs and benefits mutualists experience during the interaction. Here, we used a yeast nutritional mutualism to test how mutualists coevolve and adapt in an obligate mutualism. We allowed two yeast mutualists to evolve together for 15 weeks (about 150 generations), and then we tested if the mutualists had coevolved using time-shift assays. We also examined two mutualistic traits associated with the costs and benefits: resource use efficiency and commodity production. We found that the mutualists quickly coevolved. Furthermore, the changes in benefits and costs were nonlinear and varied with evolutionary changes occurring in the mutualist partner. One mutualist initially evolved to reduce mutualistic commodity production and increase efficiency in mutualistic resource use; however, this negatively affected its mutualist partner that evolved reduced commodity production and resource use efficiency. As a result, the former increased commodity production, resulting in an increase in benefits for its partner. The quick, nonlinear, and asynchronous evolution of yeast mutualists closely resembles antagonistic coevolutionary patterns, supporting the view that mutualisms should be considered as reciprocal exploitation., (© 2020 The Authors. Evolution © 2020 The Society for the Study of Evolution.)

Mutualisms, or reciprocally beneficial interspecific interactions, constitute the foundation of many ecological communities and agricultural systems. Mutualisms come in different forms, from pairwise interactions to extremely diverse communities, and they are continually challenged with exploitation by nonmutualistic community members (exploiters). Thus, understanding how mutualisms persist remains an essential question in ecology. Theory suggests that high species richness and functional redundancy could promote mutualism persistence in complex mutualistic communities. Using a yeast system ( Saccharomyces cerevisiae ), we experimentally show that communities with the greatest mutualist richness and functional redundancy are nearly two times more likely to survive exploitation than are simple communities. Persistence increased because diverse communities were better able to mitigate the negative effects of competition with exploiters. Thus, large mutualistic networks may be inherently buffered from exploitation., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Population divergence can occur due to mechanisms associated with geographic isolation and/or due to selection associated with different ecological niches. Much of the evidence for selection-driven speciation has come from studies of specialist insect herbivores that use different host plant species; however, the influence of host plant use on population divergence of generalist herbivores remains poorly understood. We tested how diet breadth, host plant species and geographic distance influence population divergence of the fall webworm (Hyphantria cunea; FW). FW is a broadly distributed, extreme generalist herbivore consisting of two morphotypes that have been argued to represent two different species: black-headed and red-headed. We characterized the differentiation of FW populations at two geographic scales. We first analysed the influence of host plant and geographic distance on genetic divergence across a broad continental scale for both colour types. We further analysed the influence of host plant, diet breadth and geographic distance on divergence at a finer geographic scale focusing on red-headed FW in Colorado. We found clear genetic and morphological distinction between red- and black-headed FW, and Colorado FW formed a genetic cluster distinct from other locations. Although both geographic distance and host plant use were correlated with genetic distance, geographic distance accounted for up to 3× more variation in genetic distance than did host plant use. As a rare study investigating the genetic structure of a widespread generalist herbivore over a broad geographic range (up to 3,000 km), our study supports a strong role for geographic isolation in divergence in this system., (© 2019 John Wiley & Sons Ltd.)

Herbivore-plant interactions should be studied using a tri-trophic approach, but we lack a quantitative measure of the combined effect of top-down and bottom-up forces on herbivore fitness. We propose the combination of the bi-trophic fitness slopes as a tri-trophic fitness measure. We use the relationship between fitness associated with top-down and bottom-up forces and the frequency of host plant use to calculate the top-down and bottom-up fitness slopes, which we then combine to obtain three possible directions of tri-trophic slopes. A positive tri-trophic slope indicates that herbivores have overall greater tri-trophic fitness on the more frequently used hosts. A null tri-trophic fitness slope indicates that herbivores have similar fitness on all host plants. A negative tri-trophic slope indicates that herbivores have generally lower fitness on the more frequently used hosts. We tested the explanation power of our method using data from the literature that tested herbivore host shifts and experimentally using a generalist herbivore with variable diet breadth across populations. We found that in host shifts, herbivores have higher tri-trophic fitness on the novel host, while in generalist populations, herbivores use most frequently the best host available. We present applications in other research areas and consider the limitations of our approach. Our approach is a first step towards a comprehensive model of multiple selective forces acting on the evolution of interactions., (© 2018 by the Ecological Society of America.)

Sit-and-wait predators use different strategies to encounter potential prey. Rhinoleucophenga myrmecophaga Vidal et (Vidal et Vilela; Diptera: Drosophilidae) larvae build sticky shelters on top of extrafloral nectaries (EFNs) of Qualea grandiflora Mart (Vochysiaceae), a common plant in the Brazilian cerrado savanna. Although larval shelters block the EFNs, nectar production is not obstructed and is used by the larvae to attract and trap nectar-gathering ants that are eventually eaten by the dipteran. Here we describe the natural history of R. myrmecophaga, its infestation pattern in Q. grandiflora, the ant assemblage at EFNs, and the insects used as prey. We use stable isotope composition (δ13C and δ15N) of R. myrmecophaga and potential food sources to infer its diet, and perform chemical analyses of the droplets found at shelter openings to determine whether nectar is used as a prey attractant. We found that Rhinoleucophenga larvae occur on the majority of Qualea plants and occupy active EFNs mainly in the rainy season. The two most frequent visiting species were also the most common insects found trapped at larval shelters. The stable isotope analyses confirmed that ants are the main food sources of R. myrmecophaga. Chemical analyses and field observations revealed that Rhinoleucophenga larvae use extrafloral nectar to attract prey to their shelters by pushing this liquid to the shelter opening where it forms a droplet. This is a rare case of sit-and-wait predator exploiting an ant-plant mutualism through the use of the very food reward produced by the plant to attract and capture potential ant mutualists.

Climate change is drastically altering global fire regimes, which may affect the structure and function of insect communities. Insect responses to fire are strongly tied to fire history, plant responses, and changes in species interactions. Many insects already possess adaptive traits to survive fire or benefit from post-fire resources, which may result in community composition shifting toward habitat and dietary generalists as well as species with high dispersal abilities. However, predicting community-level resilience of insects is inherently challenging due to the high degree of spatiotemporal and historical heterogeneity of fires, diversity of insect life histories, and potential interactions with other global change drivers. Future work should incorporate experimental approaches that specifically consider spatiotemporal variability and regional fire history in order to integrate eco-evolutionary processes in understanding insect responses to fire., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Initial studies using resting-state functional magnetic resonance imaging on the trajectories of the brain network from childhood to adulthood found evidence of functional integration and segregation over time. The comprehension of how healthy individuals' functional integration and segregation occur is crucial to enhance our understanding of possible deviations that may lead to brain disorders. Recent approaches have focused on the framework wherein the functional brain network is organized into spatially distributed modules that have been associated with specific cognitive functions. Here, we tested the hypothesis that the clustering structure of brain networks evolves during development. To address this hypothesis, we defined a measure of how well a brain region is clustered (network fitness index), and developed a method to evaluate its association with age. Then, we applied this method to a functional magnetic resonance imaging data set composed of 397 males under 31 years of age collected as part of the Autism Brain Imaging Data Exchange Consortium. As results, we identified two brain regions for which the clustering change over time, namely, the left middle temporal gyrus and the left putamen. Since the network fitness index is associated with both integration and segregation, our finding suggests that the identified brain region plays a role in the development of brain systems., Competing Interests: The authors have declared that no competing interests exist.

Primary consumers are under strong selection from resource ('bottom-up') and consumer ('top-down') controls, but the relative importance of these selective forces is unknown. We performed a meta-analysis to compare the strength of top-down and bottom-up forces on consumer fitness, considering multiple predictors that can modulate these effects: diet breadth, feeding guild, habitat/environment, type of bottom-up effects, type of top-down effects and how consumer fitness effects are measured. We focused our analyses on the most diverse group of primary consumers, herbivorous insects, and found that in general top-down forces were stronger than bottom-up forces. Notably, chewing, sucking and gall-making herbivores were more affected by top-down than bottom-up forces, top-down forces were stronger than bottom-up in both natural and controlled (cultivated) environments, and parasitoids and predators had equally strong top-down effects on insect herbivores. Future studies should broaden the scope of focal consumers, particularly in understudied terrestrial systems, guilds, taxonomic groups and top-down controls (e.g. pathogens), and test for more complex indirect community interactions. Our results demonstrate the surprising strength of forces exerted by natural enemies on herbivorous insects, and thus the necessity of using a tri-trophic approach when studying insect-plant interactions., (© 2017 John Wiley & Sons Ltd/CNRS.)

Purpose: As elective axillary dissection is loosing ground for early breast cancer (BC) patients both in terms of prognostic and therapeutic power, there is a growing interest in predicting patients with (nodal) high tumour burden (HTB), especially after a positive sentinel node biopsy (SNB) because they would really benefit from further axillary intervention either by complete lymph-node dissection or axillary radiation therapy., Methods/patients: Based on an analysis of 1254 BC patients in whom complete axillary clearance was performed, we devised a logistic regression (LR) model to predict those with HTB, as defined by the presence of three or more involved nodes with macrometastasis. This was accomplished through prior selection of every variable associated with HTB at univariate analysis., Results: Only those variables shown as significant at the multivariate analysis were finally considered, namely tumour size, lymphovascular invasion and histological grade. A probability table was then built to calculate the chances of HTB from a cross-correlation of those three variables. As a suggestion, if we were to follow the rationale previously used in the micrometastasis trials, a threshold of about 10% risk of HTB could be considered under which no further axillary treatment is warranted., Conclusions: Our LR model with its probability table can be used to define a subgroup of early BC patients suitable for axillary conservative procedures, either sparing completion lymph-node dissection or even SNB altogether.

Purpose: Roughly two-thirds of early breast cancer cases are associated with negative axillary nodes and do not benefit from axillary surgery at all. Accordingly, there is an ongoing search for non-surgical staging procedures to avoid lymph-node dissection or sentinel node biopsy (SNB). Non-invasive imaging techniques with very high sensitivity (Se) and negative predictive value (NPV) could eventually replace SNB. We aimed to establish the role of axillary US and MRI, alone or in combination, associated with ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in the prediction of axillary node involvement., Methods/patients: Between January 2003 and September 2015, we included 1505 of the 1538 breast cancer patients attending our centres. All patients had been referred from a single geographical area. Axillary US, magnetic resonance imaging and ultrasound-guided fine-needle aspiration biopsy (US-FNAB) were performed if required., Results: 1533 axillary US examinations and 1351 axillary MRI studies were analyzed. For axillary US, Se, Specificity (Sp), Positive Predictive Value (PPV), and NPV were 47.5, 93.6, 82.5, and 73.8%, respectively. For axillary MRI, corresponding values were 29.8, 96.6, 84.9, and 68.4%. When both tests were combined, Sp and PPV slightly improved over individual tests alone. US-FNAB showed a 100% Sp and PPV, with a Se of 80%., Conclusion: We may confidently state that axillary US and US-FNAB have to be included in the preoperative work-up of breast cancer patients.

One major problem in neuroscience is the comparison of functional brain networks of different populations, e.g., distinguishing the networks of controls and patients. Traditional algorithms are based on search for isomorphism between networks, assuming that they are deterministic. However, biological networks present randomness that cannot be well modeled by those algorithms. For instance, functional brain networks of distinct subjects of the same population can be different due to individual characteristics. Moreover, networks of subjects from different populations can be generated through the same stochastic process. Thus, a better hypothesis is that networks are generated by random processes. In this case, subjects from the same group are samples from the same random process, whereas subjects from different groups are generated by distinct processes. Using this idea, we developed a statistical test called ANOGVA to test whether two or more populations of graphs are generated by the same random graph model. Our simulations' results demonstrate that we can precisely control the rate of false positives and that the test is powerful to discriminate random graphs generated by different models and parameters. The method also showed to be robust for unbalanced data. As an example, we applied ANOGVA to an fMRI dataset composed of controls and patients diagnosed with autism or Asperger. ANOGVA identified the cerebellar functional sub-network as statistically different between controls and autism ( p < 0.001).

Background: Type 1 reaction (T1R) is an acute T-helper type 1 (Th1) inflammatory episode in patients with leprosy. While immunological responses associated with T1R have been investigated, the corresponding metabolic responses that could contribute to T1R pathology have received little attention., Methods: Metabolomics-based analyses of sera from 7 patients with and 9 without T1R were conducted via liquid chromatography-mass spectrometry. Serum metabolites present at levels that significantly differed (P < .05) with a log2 fold change of ≥ 1.0 between patient groups were interrogated against known metabolic pathways. The structural identification of targeted metabolites was confirmed and abundance changes validated by mass spectrometry and enzyme-linked immunoassay., Results: Forty metabolic pathways were perturbed in patients with T1R, with 71 dysregulated metabolites mapping to pathways for lipid mediators of inflammation. Of note was an increase in the abundance of the proinflammatory leukotriene B4 (LTB4) and a corresponding decrease in the level of proresolving resolvin D1 (RvD1). Also, levels of prostaglandin D2 (PGD2) and lipoxin A4 (LXA4) in patients with T1R were significantly increased, while the level of prostaglandin E2 (PGE2) was decreased., Conclusions: The dysregulation of metabolic pathways leading to abundance shifts between proinflammatory and proresolving lipid mediators provides a link between metabolic and cellular immune responses that result in the Th1-mediated pathology of T1R., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Understanding how brain activities cluster can help in the diagnosis of neuropsychological disorders. Thus, it is important to be able to identify alterations in the clustering structure of functional brain networks. Here, we provide an R implementation of Analysis of Cluster Variability (ANOCVA), which statistically tests (1) whether a set of brain regions of interest (ROI) are equally clustered between two or more populations and (2) whether the contribution of each ROI to the differences in clustering is significant. To illustrate the usefulness of our method and software, we apply the R package in a large functional magnetic resonance imaging (fMRI) dataset composed of 896 individuals (529 controls and 285 diagnosed with ASD-autism spectrum disorder) collected by the ABIDE (The Autism Brain Imaging Data Exchange) Consortium. Our analysis show that the clustering structure of controls and ASD subjects are different ( p < 0.001) and that specific brain regions distributed in the frontotemporal, sensorimotor, visual, cerebellar, and brainstem systems significantly contributed ( p < 0.05) to this differential clustering. These findings suggest an atypical organization of domain-specific function brain modules in ASD.

Mycobacterium leprae, the intracellular etiological agent of leprosy, infects Schwann promoting irreversible physical disabilities and deformities. These cells are responsible for myelination and maintenance of axonal energy metabolism through export of metabolites, such as lactate and pyruvate. In the present work, we observed that infected Schwann cells increase glucose uptake with a concomitant increase in glucose-6-phosphate dehydrogenase (G6PDH) activity, the key enzyme of the oxidative pentose pathway. We also observed a mitochondria shutdown in infected cells and mitochondrial swelling in pure neural leprosy nerves. The classic Warburg effect described in macrophages infected by Mycobacterium avium was not observed in our model, which presented a drastic reduction in lactate generation and release by infected Schwann cells. This effect was followed by a decrease in lactate dehydrogenase isoform M (LDH-M) activity and an increase in cellular protection against hydrogen peroxide insult in a pentose phosphate pathway and GSH-dependent manner. M. leprae infection success was also dependent of the glutathione antioxidant system and its main reducing power source, the pentose pathway, as demonstrated by a 50 and 70% drop in intracellular viability after treatment with the GSH synthesis inhibitor buthionine sulfoximine, and aminonicotinamide (6-ANAM), an inhibitor of G6PDH 6-ANAM, respectively. We concluded that M. leprae could modulate host cell glucose metabolism to increase the cellular reducing power generation, facilitating glutathione regeneration and consequently free-radical control. The impact of this regulation in leprosy neuropathy is discussed., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: This literature review covers original journal papers published between 2011 and 2015. These papers review the current status of research on the application of human factors and ergonomics in risk assessment systems' design to cope with the complexity, singularity, and danger in patient triage in primary health care., Objective: This paper presents a systematic literature review that aims to identify, analyze, and interpret the application of available evidence from human factors and ergonomics to the design of tools, devices, and work processes to support risk assessment in the context of health care., Methods: Electronic search was performed on 7 bibliographic databases of health sciences, engineering, and computer sciences disciplines. The quality and suitability of primary studies were evaluated, and selected papers were classified according to 4 classes of outcomes., Results: A total of 1845 papers were retrieved by the initial search, culminating in 16 selected for data extraction after the application of inclusion and exclusion criteria and quality and suitability evaluation., Conclusions: Results point out that the study of the implications of the lack of understanding about real work performance in designing for risk assessment in health care is very specific, little explored, and mostly focused on the development of tools., Competing Interests: Conflicts of Interest: None declared.

Lactating adenoma is an uncommon breast palpable lesion occurring in pregnancy or lactation. Although it is a benign condition, it often requires core biopsy or even surgery to exclude malignancy. As with other solid lesions in pregnancy and lactation, lactating adenoma needs an accurate evaluation in order to ensure its benign nature. Work-up must include both imaging and histologic findings. Ultrasound evaluation remains the first step in assessing the features of the lesion. Some authors consider magnetic resonance imaging as a useful tool in cases of inconclusive evaluation after ultrasound and histologic exam in an attempt to avoid surgery. Most lactating adenomas resolve spontaneously, whereas others persist or even increase in size and must be removed. The authors present a case of a 35-year-old woman at 6 months postpartum with a lactating adenoma in her right breast. After surgical removal, breastfeeding was perfectly continued within the next 24 hours, which highlights the fact that breast surgery is most often compatible with breastfeeding., (© The Author(s) 2016.)

Cytosolic detection of nucleic acids elicits a type I interferon (IFN) response and plays a critical role in host defense against intracellular pathogens. Herein, a global gene expression profile of Mycobacterium leprae-infected primary human Schwann cells identified the genes differentially expressed in the type I IFN pathway. Among them, the gene encoding 2'-5' oligoadenylate synthetase-like (OASL) underwent the greatest upregulation and was also shown to be upregulated in M. leprae-infected human macrophage cell lineages, primary monocytes, and skin lesion specimens from patients with a disseminated form of leprosy. OASL knock down was associated with decreased viability of M. leprae that was concomitant with upregulation of either antimicrobial peptide expression or autophagy levels. Downregulation of MCP-1/CCL2 release was also observed during OASL knock down. M. leprae-mediated OASL expression was dependent on cytosolic DNA sensing mediated by stimulator of IFN genes signaling. The addition of M. leprae DNA enhanced nonpathogenic Mycobacterium bovis bacillus Calmette-Guerin intracellular survival, downregulated antimicrobial peptide expression, and increased MCP-1/CCL2 secretion. Thus, our data uncover a promycobacterial role for OASL during M. leprae infection that directs the host immune response toward a niche that permits survival of the pathogen., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

An open question in the evolutionary ecology of ant-plant facultative mutualism is how other members of the associated community can affect the interaction to a point where reciprocal benefits are disrupted. While visiting Qualea grandiflora shrubs to collect sugary rewards at extrafloral nectaries, tropical savanna ants deter herbivores and reduce leaf damage. Here we show that larvae of the fly Rhinoleucophenga myrmecophaga, which develop on extrafloral nectaries, lure potentially mutualistic, nectar-feeding ants and prey on them. Foraging ants spend less time on fly-infested foliage. Field experiments showed that predation (or the threat of predation) on ants by fly larvae produces cascading effects through three trophic levels, resulting in fewer protective ants on leaves, increased numbers of chewing herbivores, and greater leaf damage. These results reveal an undocumented mode of mutualism exploitation by an opportunistic predator at a plant-provided food source, jeopardizing ant-derived protection services to the plant. Our study documents a rather unusual case of predation of adult ants by a dipteran species and demonstrates a top-down trophic cascade within a generalized ant-plant mutualism., (© 2016 by the Ecological Society of America.)

Mycobacterium leprae (ML), the etiologic agent of leprosy, can subvert macrophage antimicrobial activity by mechanisms that remain only partially understood. In the present study, the participation of hormone insulin-like growth factor I (IGF-I) in this phenomenum was investigated. Macrophages from the dermal lesions of the disseminated multibacillary lepromatous form (LL) of leprosy expressed higher levels of IGF-I than those from the self-limited paucibacillary tuberculoid form (BT). Higher levels of IGF-I secretion by ML-infected macrophages were confirmed in ex vivo and in vitro studies. Of note, the dampening of IGF-I signaling reverted the capacity of ML-infected human and murine macrophages to produce antimicrobial molecules and promoted bacterial killing. Moreover, IGF-I was shown to inhibit the JAK/STAT1-dependent signaling pathways triggered by both mycobacteria and IFN-γ most probably through its capacity to induce the suppressor of cytokine signaling-3 (SOCS3). Finally, these in vitro findings were corroborated by in vivo observations in which higher SOCS3 expression and lower phosphorylation of STAT1 levels were found in LL versus BT dermal lesions. Altogether, our data strongly suggest that IGF-I contributes to the maintenance of a functional program in infected macrophages that suits ML persistence in the host, reinforcing a key role for IGF-I in leprosy pathogenesis.

Leprosy is a chronic dermato-neurological disease caused by infection with Mycobacterium leprae. In 2013 almost 200,000 new cases of leprosy were detected around the world. Since the first symptoms take from years to decades to appear, the total number of asymptomatic patients is impossible to predict. Although leprosy is one of the oldest records of human disease, the mechanisms involved with its transmission and epidemiology are still not completely understood. In the present work, we experimentally investigated the hypothesis that the mosquitoes Aedes aegypti and Culex quinquefasciatus and the hemiptera Rhodnius prolixus act as leprosy vectors. By means of real-time PCR quantification of M. leprae 16SrRNA, we found that M. leprae remained viable inside the digestive tract of Rhodnius prolixus for 20 days after oral infection. In contrast, in the gut of both mosquito species tested, we were not able to detect M. leprae RNA after a similar period of time. Inside the kissing bug Rhodnius prolixus digestive tract, M. leprae was initially restricted to the anterior midgut, but gradually moved towards the hindgut, in a time course reminiscent of the life cycle of Trypanosoma cruzi, a well-known pathogen transmitted by this insect. The maintenance of M. leprae infectivity inside the digestive tract of this kissing bug is further supported by successful mice footpad inoculation with feces collected 20 days after infection. We conclude that Rhodnius prolixus defecate infective M. leprae, justifying the evaluation of the presence of M. leprae among sylvatic and domestic kissing bugs in countries endemic for leprosy.

Background: Several neuroimaging studies support the model of abnormal development of brain connectivity in patients with autism-spectrum disorders (ASD). In this study, we aimed to test the hypothesis of reduced functional network segregation in autistic patients compared with controls., Methods: Functional MRI data from children acquired under a resting-state protocol (Autism Brain Imaging Data Exchange [ABIDE]) were submitted to both fuzzy spectral clustering (FSC) with entropy analysis and graph modularity analysis., Results: We included data from 814 children in our analysis. We identified 5 regions of interest comprising the motor, temporal and occipitotemporal cortices with increased entropy (p < 0.05) in the clustering structure (i.e., more segregation in the controls). Moreover, we noticed a statistically reduced modularity (p < 0.001) in the autistic patients compared with the controls. Significantly reduced eigenvector centrality values (p < 0.05) in the patients were observed in the same regions that were identified in the FSC analysis., Limitations: There is considerable heterogeneity in the fMRI acquisition protocols among the sites that contributed to the ABIDE data set (e.g., scanner type, pulse sequence, duration of scan and resting-state protocol). Moreover, the sites differed in many variables related to sample characterization (e.g., age, IQ and ASD diagnostic criteria). Therefore, we cannot rule out the possibility that additional differences in functional network organization would be found in a more homogeneous data sample of individuals with ASD., Conclusion: Our results suggest that the organization of the whole-brain functional network in patients with ASD is different from that observed in controls, which implies a reduced modularity of the brain functional networks involved in sensorimotor, social, affective and cognitive processing.

Introduction: Screening programs for breast cancer aim to allow early diagnosis, and thus reduce mortality. The aim of this study was to assess the effect of a population screening program in a sample of women aged between 50 and 69 years in terms of recurrence, metastasis, biological profiles, and survival, and to compare their results with those of women of a wider age range who did not participate on the screening program., Patients and Methods: A prospective multicenter study in which 1821 patients with 1873 breast tumors who received surgery between 1999 and 2014 at MútuaTerrassa University Hospital and the Hospital of Terrassa in Barcelona were analyzed. A comparison was performed in the 50- to 69-year-old age group between those who participated on the screening program and those who did not., Results: The mean age of patients was 58 years. The mean follow-up was 72 months, and median follow-up 59 months. The screened group showed significantly better results in all prognostic factors and in specific mortality than all nonscreened groups. The specific mortality rate in the screened patients was 2.4% (12/496), local recurrence 2.8% (14/496), and metastasis at 10 years 3.6% (18/496). In the nonscreened group, younger women presented a higher rate of metastasis (16.4% [81/493]) and a shorter disease-free period (77.1% [380/493]). The age group older than 70 years had the highest number of T4 tumors (7.5% [30/403]) and the highest proportion of radical surgery (50.4% [203/403])., Conclusion: Patients in the screening program presented improved survival. We speculate that extending breast cancer screening programs to women younger than 50 and older than 70 years could bring about mortality benefits., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Epilepsy affects approximately 3% of the world's population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17% of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24% of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which primarily infects macrophages and Schwann cells, affecting skin and peripheral nerves. Clinically, the most common form of identification is through the observation of anesthetic lesions on skin; however, up to 30% of infected patients may not present this clinical manifestation. Currently, the gold standard diagnostic test for leprosy is based on skin lesion biopsy, which is invasive and presents low sensibility for suspect cases. Therefore, the development of a fast, sensible and noninvasive method that identifies infected patients would be helpful for assertive diagnosis. The aim of this work was to identify lipid markers in leprosy patients directly from skin imprints, using a mass spectrometric analytical strategy. For skin imprint samples, a 1 cm(2) silica plate was gently pressed against the skin of patients or healthy volunteers. Imprinted silica lipids were extracted and submitted to direct-infusion electrospray ionization high-resolution mass spectrometry (ESI-HRMS). All samples were differentiated using a lipidomics-based data workup employing multivariate data analysis, which helped electing different lipid markers, for example, mycobacterial mycolic acids, inflammatory and apoptotic molecules were identified as leprosy patients' markers. Otherwise, phospholipids and gangliosides were pointed as healthy volunteers' skin lipid markers, according to normal skin composition. Results indicate that silica plate skin imprinting associated with ESI-HRMS is a promising fast and sensible leprosy diagnostic method. With a prompt leprosy diagnosis, an early and effective treatment could be feasible and thus the chain of leprosy transmission could be abbreviated.

Blood-stained colostrum occurs occasionally during pregnancy and lactation due to a conspicuous increase in lobuloalveolar growth. We report on a case of bilateral frank blood-stained colostrum secreted during pregnancy and early postpartum, emphasizing the transitory nature of this condition and the need to reinforce breastfeeding., (© The Author(s) 2014.)

Mycobacterium leprae and Mycobacterium tuberculosis antimicrobial resistance has been followed with great concern during the last years, while the need for new drugs able to control leprosy and tuberculosis, mainly due to extensively drug-resistant tuberculosis (XDR-TB), is pressing. Our group recently showed that M. leprae is able to induce lipid body biogenesis and cholesterol accumulation in macrophages and Schwann cells, facilitating its viability and replication. Considering these previous results, we investigated the efficacies of two statins on the intracellular viability of mycobacteria within the macrophage, as well as the effect of atorvastatin on M. leprae infections in BALB/c mice. We observed that intracellular mycobacteria viability decreased markedly after incubation with both statins, but atorvastatin showed the best inhibitory effect when combined with rifampin. Using Shepard's model, we observed with atorvastatin an efficacy in controlling M. leprae and inflammatory infiltrate in the BALB/c footpad, in a serum cholesterol level-dependent way. We conclude that statins contribute to macrophage-bactericidal activity against Mycobacterium bovis, M. leprae, and M. tuberculosis. It is likely that the association of statins with the actual multidrug therapy effectively reduces mycobacterial viability and tissue lesion in leprosy and tuberculosis patients, although epidemiological studies are still needed for confirmation., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Introduction: The Republic of Djibouti is an African country that exhibits one of the highest incidence rate of tuberculosis in the world. The aim of this study was to evaluate the prevalence of multidrug-resistant tuberculosis among new cases., Methodology: We studied retrospectively every tuberculosis case diagnosed over a 12-month period in patients hospitalized at the French Military Hospital of Bouffard. During this period, 1,274 samples from 675 patients were tested., Results: We isolated 266 mycobacteria corresponding to 180 cases of tuberculosis. Thirty-three were fully susceptible and 57% met the tuberculosis criteria, with 46% primary resistance. No extensively-drug-resistant tuberculosis was found., Conclusion: Our results highlight a major concern about the situation in this part of the world.

Aim: To assess the fecal immunochemical test (FIT) accuracy for colorectal cancer (CRC) and advanced neoplasia (AN) detection in CRC screening., Methods: We performed a multicentric, prospective, double blind study of diagnostic tests on asymptomatic average-risk individuals submitted to screening colonoscopy. Two stool samples were collected and the fecal hemoglobin concentration was determined in the first sample (FIT1) and the highest level of both samples (FITmax) using the OC-sensor™. Areas under the curve (AUC) for CRC and AN were calculated. The best FIT1 and FITmax cut-off values for CRC were determined. At this threshold, number needed to scope (NNS) to detect a CRC and an AN and the cost per lesion detected were calculated., Results: About 779 individuals were included. An AN was found in 97 (12.5%) individuals: a CRC in 5 (0.6%) and an advanced adenoma (≥ 10 mm, villous histology or high grade dysplasia) in 92 (11.9%) subjects. For CRC diagnosis, FIT1 AUC was 0.96 (95%CI: 0.95-0.98) and FITmax AUC was 0.95 (95%CI: 0.93-0.97). For AN, FIT1 and FITmax AUC were similar (0.72, 95%CI: 0.66-0.78 vs 0.73, 95%CI: 0.68-0.79, respectively, P = 0.34). Depending on the number of determinations and the positivity threshold cut-off used sensitivity for AN detection ranged between 28% and 42% and specificity between 91% and 97%. At the best cut-off point for CRC detection (115 ng/mL), the NNS to detect a CRC were 10.2 and 15.8; and the cost per CRC was 1814€ and 2985€ on FIT1 and FITmax strategies respectively. At this threshold the sensitivity, NNS and cost per AN detected were 30%, 1.76, and 306€, in FIT1 strategy, and 36%, 2.26€ and 426€, in FITmax strategy, respectively., Conclusion: Performing two tests does not improve diagnostic accuracy, but increases cost and NNS to detect a lesion.

Herein, we performed microarray experiments in Schwann cells infected with live M. leprae and identified novel differentially expressed genes (DEG) in M. leprae infected cells. Also, we selected candidate genes associated or implicated with leprosy in genetic studies and biological experiments. Forty-seven genes were selected for validation in two independent types of samples by multiplex qPCR. First, an in vitro model using THP-1 cells was infected with live Mycobacterium leprae and M. bovis bacillus Calmette-Guérin (BCG). In a second situation, mRNA obtained from nerve biopsies from patients with leprosy or other peripheral neuropathies was tested. We detected DEGs that discriminate M. bovis BCG from M. leprae infection. Specific signatures of susceptible responses after M. leprae infection when compared to BCG lead to repression of genes, including CCL2, CCL3, IL8 and SOD2. The same 47-gene set was screened in nerve biopsies, which corroborated the down-regulation of CCL2 and CCL3 in leprosy, but also evidenced the down-regulation of genes involved in mitochondrial metabolism, and the up-regulation of genes involved in lipid metabolism and ubiquitination. Finally, a gene expression signature from DEG was identified in patients confirmed of having leprosy. A classification tree was able to ascertain 80% of the cases as leprosy or non-leprous peripheral neuropathy based on the expression of only LDLR and CCL4. A general immune and mitochondrial hypo-responsive state occurs in response to M. leprae infection. Also, the most important genes and pathways have been highlighted providing new tools for early diagnosis and treatment of leprosy.

Leprosy is an infectious disease caused by Mycobacterium leprae that affects the skin and nerves, presenting a singular clinical picture. Across the leprosy spectrum, lepromatous leprosy (LL) exhibits a classical hallmark: the presence of a collection of M. leprae-infected foamy macrophages/Schwann cells characterised by their high lipid content. The significance of this foamy aspect in mycobacterial infections has garnered renewed attention in leprosy due to the recent observation that the foamy aspect represents cells enriched in lipid droplets (LD) (also known as lipid bodies). Here, we discuss the contemporary view of LD as highly regulated organelles with key functions in M. leprae persistence in the LL end of the spectrum. The modern methods of studying this ancient disease have contributed to recent findings that describe M. leprae-triggered LD biogenesis and recruitment as effective mycobacterial intracellular strategies for acquiring lipids, sheltering and/or dampening the immune response and favouring bacterial survival, likely representing a fundamental aspect of M. leprae pathogenesis. The multifaceted functions attributed to the LD in leprosy may contribute to the development of new strategies for adjunctive anti-leprosy therapies.

We analysed 16 variable number tandem repeats (VNTR) and three single-nucleotide polymorphisms (SNP) in Mycobacterium leprae present on 115 Ziehl-Neelsen (Z-N)-stained slides and in 51 skin biopsy samples derived from leprosy patients from Ceará (n = 23), Pernambuco (n = 41), Rio de Janeiro (n = 22) and Rondônia (RO) (n = 78). All skin biopsies yielded SNP-based genotypes, while 48 of the samples (94.1%) yielded complete VNTR genotypes. We evaluated two procedures for extracting M. leprae DNA from Z-N-stained slides: the first including Chelex and the other combining proteinase and sodium dodecyl sulfate. Of the 76 samples processed using the first procedure, 30.2% were positive for 16 or 15 VNTRs, whereas of the 39 samples processed using the second procedure, 28.2% yielded genotypes defined by at least 10 VNTRs. Combined VNTR and SNP analysis revealed large variability in genotypes, but a high prevalence of SNP genotype 4 in the Northeast Region of Brazil. Our observation of two samples from RO with an identical genotype and seven groups with similar genotypes, including four derived from residents of the same state or region, suggest a tendency to form groups according to the origin of the isolates. This study demonstrates the existence of geographically related M. leprae genotypes and that Z-N-stained slides are an alternative source for M. leprae genotyping.

Silent transmission of Mycobacterium leprae, as evidenced by stable leprosy incidence rates in various countries, remains a health challenge despite the implementation of multidrug therapy worldwide. Therefore, the development of tools for the early diagnosis of M. leprae infection should be emphasised in leprosy research. As part of the continuing effort to identify antigens that have diagnostic potential, unique M. leprae peptides derived from predicted virulence-associated proteins (group IV.A) were identified using advanced genome pattern programs and bioinformatics. Based on human leukocyte antigen (HLA)-binding motifs, we selected 21 peptides that were predicted to be promiscuous HLA-class I T-cell epitopes and eight peptides that were predicted to be HLA-class II restricted T-cell epitopes for field-testing in Brazil, Ethiopia and Nepal. High levels of interferon (IFN)-γ were induced when peripheral blood mononuclear cells (PBMCs) from tuberculoid/borderline tuberculoid leprosy patients located in Brazil and Ethiopia were stimulated with the ML2055 p35 peptide. PBMCs that were isolated from healthy endemic controls living in areas with high leprosy prevalence (EChigh) in Ethiopia also responded to the ML2055 p35 peptide. The Brazilian EChigh group recognised the ML1358 p20 and ML1358 p24 peptides. None of the peptides were recognised by PBMCs from healthy controls living in non-endemic region. In Nepal, mixtures of these peptides induced the production of IFN-γ by the PBMCs of leprosy patients and EChigh. Therefore, the M. leprae virulence-associated peptides identified in this study may be useful for identifying exposure to M. leprae in population with differing HLA polymorphisms.

When grown in the presence of exogenous collagen I, Mycobacterium bovis BCG was shown to form clumps. Scanning electron microscopy examination of these clumps revealed the presence of collagen fibres cross-linking the bacilli. Since collagen is a major constituent of the eukaryotic extracellular matrices, we assayed BCG cytoadherence in the presence of exogenous collagen I. Collagen increased the interaction of the bacilli with A549 type II pneumocytes or U937 macrophages, suggesting that BCG is able to recruit collagen to facilitate its attachment to host cells. Using an affinity chromatography approach, we have isolated a BCG collagen-binding protein corresponding to the previously described mycobacterial laminin-binding histone-like protein (LBP/Hlp), a highly conserved protein associated with the mycobacterial cell wall. Moreover, Mycobacterium leprae LBP/Hlp, a well-characterized adhesin, was also able to bind collagen I. Finally, using recombinant fragments of M. leprae LBP/Hlp, we mapped the collagen-binding activity within the C-terminal domain of the adhesin. Since this protein was already shown to be involved in the recognition of laminin and heparan sulphate-containing proteoglycans, the present observations reinforce the adhesive activities of LBP/Hlp, which can be therefore considered as a multifaceted mycobacterial adhesin, playing an important role in both leprosy and tuberculosis pathogenesis.

Introduction: According to Spanish health regulations, primary care professionals have the responsibility to carry out health-promoting community activities (CAs). However, in practice, their implementation is not as widespread as it should be. The aims of this study were to identify factors within the team, the community and the professionals that influence the development of these activities and to describe the community interventions in progress., Methods and Analysis: This study is an observational analytical retrospective study. The information will be collected from five Spanish regions: Catalonia, Madrid, the Balearic Islands, Navarra and Aragón. The authors will contact primary care teams (PCTs) and identify the CAs from the previous year. The research team will conduct a peer review whether the inclusion criteria are met. In the health centres where CAs are implemented, the authors will select professionals carrying them out and randomly select an identical number of professionals not doing these activities. In the centres where no CA is implemented, three professionals will be randomly selected. The selected professionals will complete the questionnaires for individual-level variables. Information about the registered population and the PCTs will be collected through questionnaires and secondary sources., Outcomes: Variables will be collected from the community, the PCTs, the individual professionals and CAs., Analysis: A descriptive analysis of all the variables will be carried out, along with a bivariate and a logistic regression analysis, with CAs being the primary outcome., Ethics and Dissemination: This study has been approved by the Research Ethics Committee of the Jordi Gol y Gurina Foundation in Barcelona and area 11 in Madrid. The questionnaire distributed to the professionals will be anonymous.

This paper presents a protocol for work distress assessment. Work distress is defined as a merge between nonergonomic related aspects, in tasks or environment, and adversely conditions perceived for a worker, in a certain work situation. This frame requires an approach that can treat individuals and organizational factors in the same way, at the same time. For this, we elaborate a psycho-ergonomics method, associating concepts and practices from cognitive-behavioral techniques and work ergonomic analysis, which we named CEWAT - Cognitive-Behavioral Work Analysis Technique. This paper presents CEWAT's foundations and structure, in steps. An application to a complex and dangerous system illustrates its benefits in the ergonomics action.

In this paper, we analyzed two laboratories of liquid chromatography (LC), separation technique of mixtures and identification of its components, in order to identify projectual gaps relating to the environment and the working station. The methodology used was the ergonomic analysis with interactional and participatory techniques applied during the activity performance. This work incorporated and adapted the concept developed by Alexander (1979)--pattern languages--passing from architectural projects to workstations project and physical arrangement of the work environment. The adaptation of the concept resulted in a list of recommendations, requirements and concepts that have brought design solutions for the problematic aspects observed in the ergonomic analysis. The employed methodology, strongly supported in ergonomics principles, and in interactional and participatory techniques, contributed to achieve our gold that is what we now call Conceptual Standards. The patterns go beyond of a usual model of book a of ergonomics specification, once incorporating the viewpoint of the end user, it is also a set of best project practices and of project management in conception ergonomics.