Cryptococcal Virulence in Humans: Learning From Translational Studies With Clinical Isolates

Cryptococcosis, an invasive mycosis caused by Cryptococcus spp, kills between 20% and 70% of the patients who develop it. There are no vaccines for prevention, and treatment is based on a limited number of antifungals. Studying fungal virulence and how the host responds to infection could lead to new therapies, improving outcomes for patients. The biggest challenge, however, is that experimental cryptococcosis models do not completely recapitulate human disease, while human experiments are limited due to ethical reasons. To overcome this challenge, one of the approaches used by researchers and clinicians is to: 1) collect cryptococcal clinical isolates and associated patient data; 2) study the set of isolates in the laboratory (virulence and host-pathogen interaction variables, molecular markers); 3) correlate the laboratory and patient data to understand the roles fungal attributes play in the human disease. Here we review studies that have shed light on the cryptococcosis pathophysiology using these approaches, with a special focus on human disease. Isolates that more effectively evade macrophage responses, that secrete more laccase, melanize faster and have larger capsules in the cerebrospinal fluid are associated with poorer patient outcomes. Additionally, molecular studies have also shown that cryptococcal clades vary in virulence, with clinical impact. Limitations of those studies include the use of a small number of isolates or retrospectively collected clinical data. The fact that they resulted in very important information is a reflection of the impact this strategy has in understanding cryptococcosis and calls for international collaboration that could boost our knowledge.

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What Determines Fiscal Deficits in Europe? The Impact and Interaction of EMU Membership, Fiscal Rules, Fiscal Councils and Creative Accounting

Review of Economics ◽

10.1515/roe-2020-0004 ◽

2020 ◽

Vol 71 (1) ◽

pp. 15-41

Author(s):

Dominik Maltritz ◽

Sebastian Wüste

Keyword(s):

Fiscal Rules ◽

Special Focus ◽

Annual Data ◽

Budget Balance ◽

Fiscal Deficits ◽

Eu Countries ◽

Creative Accounting ◽

Stock Flow ◽

The Impact

AbstractWe search for drivers of fiscal deficits in Europe using a data panel containing annual data of 27 EU countries in the years 1991–2012. Our special focus is on the influence of fiscal rules as well as on fiscal councils, i. e. institutions that may help to reduce deficits and enforce fiscal rules by advising governments. We distinguish between internal fiscal rules and external rules that result from EMU membership. In addition, we consider the impact of “creative accounting”, i. e. measures that help to circumvent fiscal rules, which we approximate by so called stock-flow-adjustments. We especially analyze the interactive influence of the mentioned variables on the budget balance.

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26.A. Workshop: Assessing the role of policies and actions to address childhood obesity

European Journal of Public Health ◽

10.1093/eurpub/ckaa165.1225 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

◽

Keyword(s):

Public Health ◽

Childhood Obesity ◽

Stakeholder Engagement ◽

Special Focus ◽

Policy Options ◽

Sustainable Solutions ◽

Relevant Evidence ◽

Multi Stakeholder ◽

The Impact

Abstract Childhood obesity has grown to become one of the most dramatic features of the global obesity epidemic, with long-term consequences. The spread of obesity has been fueled by changes in social norms and living environments that have shaped individual behaviours making them conducive to excessive and imbalanced nutrition, sedentary lifestyles, and ultimately obesity and associated diseases. The STOP project will aim to generate scientifically sound, novel and policy-relevant evidence on the factors that have contributed to the spread of childhood obesity in European countries and on the effects of alternative technological and organisational solutions and policy options available to address the problem. STOP will translate the evidence gathered and generated into indicators and measurements, policy briefs and toolkits and multi-stakeholder frameworks. A special focus of STOP is understanding the stakeholders' networks and drivers of stakeholders' action. STOP will establish new ways for policy-relevant evidence to be generated, made available and used in the design and implementation of effective and sustainable solutions for childhood obesity at the EU, national and local levels. Each of the policy work packages will: Produce evidence syntheses and impact simulations for different policy approaches;Assess selected policy approaches and actions in children cohorts and other relevant settings;Devise policy toolkits and policy guidance to support the adoption and implementation of specific actions by relevant actors;Establish a country-based European accountability and monitoring framework in each policy area. The workshop aims to: Showcase the impact of different policy options evaluated throughout the STOP project;Increase participants' understanding and awareness of the opportunities and challenges associated with the implementation of selected policies;Increase awareness of public health professionals of the importance of overcoming siloes in identifying and implementing public health policies;Increase the understanding of multi-stakeholder engagement. The discussion will explore the role of stakeholders across different policy areas. We will explore the different definitions of “stakeholders” and “multi-stakeholders” engagement. This will also be an opportunity to explore some of the benefits, risks and challenges around stakeholder engagement, and explore what are the different types of stakeholders involved in these policies as well as their roles. The workshop will offer an opportunity to: Inform participants about existing physical activity, regulatory and fiscal policies to address childhood obesity;Inform participants about new, innovative EU-level projects that aim to address childhood obesity;Outline preliminary findings of the STOP project with regards to the effectiveness of the evaluated policies;Identify some of the gaps and limitations of existing policies and discuss some of the steps to ensure successful policy implementation. Key messages Present new evidence on what policy approaches work in addressing key determinants of childhood obesity. Showcase findings on the attitudes of different stakeholders towards obesity policies, and debate the benefits, risks and challenges of multi-stakeholder engagement.

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The impact of bZIP Atf1ortholog global regulators in fungi

Applied Microbiology and Biotechnology ◽

10.1007/s00253-021-11431-7 ◽

2021 ◽

Author(s):

Éva Leiter ◽

Tamás Emri ◽

Klaudia Pákozdi ◽

László Hornok ◽

István Pócsi

Keyword(s):

Transcription Factors ◽

Stress Response ◽

Secondary Metabolite ◽

Plant Pathogens ◽

Leucine Zipper ◽

Secondary Metabolite Production ◽

Special Focus ◽

Human Pathogens ◽

Metabolite Production ◽

The Impact

Abstract Regulation of signal transduction pathways is crucial for the maintenance of cellular homeostasis and organismal development in fungi. Transcription factors are key elements of this regulatory network. The basic-region leucine zipper (bZIP) domain of the bZIP-type transcription factors is responsible for DNA binding while their leucine zipper structural motifs are suitable for dimerization with each other facilitiating the formation of homodimeric or heterodimeric bZIP proteins. This review highlights recent knowledge on the function of fungal orthologs of the Schizosaccharomyces pombe Atf1, Aspergillus nidulans AtfA, and Fusarium verticillioides FvAtfA, bZIP-type transcription factors with a special focus on pathogenic species. We demonstrate that fungal Atf1-AtfA-FvAtfA orthologs play an important role in vegetative growth, sexual and asexual development, stress response, secondary metabolite production, and virulence both in human pathogens, including Aspergillus fumigatus, Mucor circinelloides, Penicillium marneffei, and Cryptococcus neoformans and plant pathogens, like Fusarium ssp., Magnaporthe oryzae, Claviceps purpurea, Botrytis cinerea, and Verticillium dahliae. Key points • Atf1 orthologs play crucial role in the growth and development of fungi. • Atf1 orthologs orchestrate environmental stress response of fungi. • Secondary metabolite production and virulence are coordinated by Atf1 orthologs.

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The impact of the Corona crisis on borderland living in the Danish-German border region with a special focus on the two national minorities

National Identities ◽

10.1080/14608944.2021.1938522 ◽

2021 ◽

pp. 1-18

Author(s):

Ruairidh Tarvet ◽

Martin Klatt

Keyword(s):

Border Region ◽

Special Focus ◽

National Minorities ◽

The Impact

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Environmental Changes and Cultural Transitions in SW Iberia during the Early-Mid Holocene

Applied Sciences ◽

10.3390/app11083580 ◽

2021 ◽

Vol 11 (8) ◽

pp. 3580

Author(s):

Cristina Val-Peón ◽

Juan I. Santisteban ◽

José A. López-Sáez ◽

Gerd-Christian Weniger ◽

Klaus Reicherter

Keyword(s):

Dietary Habits ◽

Environmental Changes ◽

Source Area ◽

Direct Access ◽

Special Focus ◽

Early Neolithic ◽

Archaeological Data ◽

Local Resources ◽

Climate Events ◽

The Impact

The SW coast of the Iberian Peninsula experiences a lack of palaeoenvironmental and archaeological data. With the aim to fill this gap, we contribute with a new palynological and geochemical dataset obtained from a sediment core drilled in the continental shelf of the Algarve coast. Archaeological data have been correlated with our multi-proxy dataset to understand how human groups adapted to environmental changes during the Early-Mid Holocene, with special focus on the Mesolithic to Neolithic transition. Vegetation trends indicate warm conditions at the onset of the Holocene followed by increased moisture and forest development ca. 10–7 ka BP, after which woodlands are progressively replaced by heaths. Peaks of aridity were identified at 8.2 and 7. 5 ka BP. Compositional, textural, redox state, and weathering of source area geochemical proxies indicates abrupt palaeoceanographic modifications and gradual terrestrial changes at 8.2 ka BP, while the 7.5 ka BP event mirrors a decrease in land moisture availability. Mesolithic sites are mainly composed of seasonal camps with direct access to the coast for the exploitation of local resources. This pattern extends into the Early Neolithic, when these sites coexist with seasonal and permanent occupations located in inland areas near rivers. Changes in settlement patterns and dietary habits may be influenced by changes in coastal environments caused by the sea-level rise and the impact of the 8.2 and 7.5 ka BP climate events.

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Erythrocytes: Central Actors in Multiple Scenes of Atherosclerosis

International Journal of Molecular Sciences ◽

10.3390/ijms22115843 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5843

Author(s):

Chloé Turpin ◽

Aurélie Catan ◽

Olivier Meilhac ◽

Emmanuel Bourdon ◽

François Canonne-Hergaux ◽

...

Keyword(s):

Iron Homeostasis ◽

The Body ◽

Diabetic Patients ◽

Special Focus ◽

Plaque Progression ◽

Cell Dysfunction ◽

Circulating Cells ◽

The Impact ◽

Progression Of Atherosclerosis

The development and progression of atherosclerosis (ATH) involves lipid accumulation, oxidative stress and both vascular and blood cell dysfunction. Erythrocytes, the main circulating cells in the body, exert determinant roles in the gas transport between tissues. Erythrocytes have long been considered as simple bystanders in cardiovascular diseases, including ATH. This review highlights recent knowledge concerning the role of erythrocytes being more than just passive gas carriers, as potent contributors to atherosclerotic plaque progression. Erythrocyte physiology and ATH pathology is first described. Then, a specific chapter delineates the numerous links between erythrocytes and atherogenesis. In particular, we discuss the impact of extravasated erythrocytes in plaque iron homeostasis with potential pathological consequences. Hyperglycaemia is recognised as a significant aggravating contributor to the development of ATH. Then, a special focus is made on glycoxidative modifications of erythrocytes and their role in ATH. This chapter includes recent data proposing glycoxidised erythrocytes as putative contributors to enhanced atherothrombosis in diabetic patients.

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Immunoglobulin levels in systemic lupus erythematosus: A narrative review

Lupus ◽

10.1177/09612033211004714 ◽

2021 ◽

pp. 096120332110047

Author(s):

Ibrahim Almaghlouth ◽

Sindhu R Johnson ◽

Eleanor Pullenayegum ◽

Dafna Gladman ◽

Murray Urowitz

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Narrative Review ◽

Special Focus ◽

Immunoglobulin Level ◽

Systemic Lupus ◽

External Threats ◽

Self Tolerance ◽

Low Levels ◽

The Impact

Immunoglobulins play a fundamental role in the protection of the human body against internal and external threats. They also contribute to the immune system homeostasis and maintenance of self-tolerance. Hypogammaglobulinemia is occasionally encountered in routine clinical practice by rheumatologists. Low levels of immunoglobulins can occur as primary or secondary issues and may predispose patients to various forms of infection. However, the impact of the low immunoglobulin level abnormality varies with the underlying condition. In this narrative review, we shed light on the overall types and functions of immunoglobulins for clinicians. We discuss important principles of immunoglobulin measurements. We then consider the primary and secondary causes of low immunoglobulins with a special focus on hypogammaglobulinemia in patients with systemic lupus erythematosus (SLE).

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Impact of Land Use Change on Water Conservation: A Case Study of Zhangjiakou in Yongding River

Sustainability ◽

10.3390/su13010022 ◽

2020 ◽

Vol 13 (1) ◽

pp. 22

Author(s):

Tianshi Pan ◽

Lijun Zuo ◽

Zengxiang Zhang ◽

Xiaoli Zhao ◽

Feifei Sun ◽

...

Keyword(s):

Land Use ◽

Sustainable Development ◽

Water Conservation ◽

Land Use Changes ◽

Water Yield ◽

Special Focus ◽

Hydrological Process ◽

Significant Difference ◽

The Impact ◽

Yongding River

The implementation of ecological projects can largely change regional land use patterns, in turn altering the local hydrological process. Articulating these changes and their effects on ecosystem services, such as water conservation, is critical to understanding the impacts of land use activities and in directing future land planning toward regional sustainable development. Taking Zhangjiakou City of the Yongding River as the study area—a region with implementation of various ecological projects—the impact of land use changes on various hydrological components and water conservation capacity from 2000 to 2015 was simulated based on a soil and water assessment tool model (SWAT). An empirical regression model based on partial least squares was established to explore the contribution of different land use changes on water conservation. With special focus on the forest having the most complex effects on the hydrological process, the impacts of forest type and age on the water conservation capacity are discussed on different scales. Results show that between 2000 and 2015, the area of forest, grassland and cultivated land decreased by 0.05%, 0.98% and 1.64%, respectively, which reduces the regional evapotranspiration (0.48%) and soil water content (0.72%). The increase in settlement area (42.23%) is the main reason for the increase in water yield (14.52%). Most land use covered by vegetation has strong water conservation capacity, and the water conservation capacity of the forest is particularly outstanding. Farmland and settlements tend to have a negative effect on water conservation. The water conservation capacity of forest at all scales decreased significantly with the growth of forest (p < 0.05), while the water conservation capacity of different tree species had no significant difference. For the study area, increasing the forest area will be an effective way to improve the water conservation function, planting evergreen conifers can rapidly improve the regional water conservation capacity, while planting deciduous conifers is of great benefit to long-term sustainable development.

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When does the use of individual patient data in network meta-analysis make a difference? A simulation study

BMC Medical Research Methodology ◽

10.1186/s12874-020-01198-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Steve Kanters ◽

Mohammad Ehsanul Karim ◽

Kristian Thorlund ◽

Aslam Anis ◽

Nick Bansback

Keyword(s):

Simulation Study ◽

Treatment Effect ◽

Mean Squared Error ◽

Individual Patient Data ◽

Meta Analysis ◽

Model Performance ◽

Patient Data ◽

Meta Regression ◽

Treatment Comparisons ◽

The Impact

Abstract Background The use of individual patient data (IPD) in network meta-analyses (NMA) is rapidly growing. This study aimed to determine, through simulations, the impact of select factors on the validity and precision of NMA estimates when combining IPD and aggregate data (AgD) relative to using AgD only. Methods Three analysis strategies were compared via simulations: 1) AgD NMA without adjustments (AgD-NMA); 2) AgD NMA with meta-regression (AgD-NMA-MR); and 3) IPD-AgD NMA with meta-regression (IPD-NMA). We compared 108 parameter permutations: number of network nodes (3, 5 or 10); proportion of treatment comparisons informed by IPD (low, medium or high); equal size trials (2-armed with 200 patients per arm) or larger IPD trials (500 patients per arm); sparse or well-populated networks; and type of effect-modification (none, constant across treatment comparisons, or exchangeable). Data were generated over 200 simulations for each combination of parameters, each using linear regression with Normal distributions. To assess model performance and estimate validity, the mean squared error (MSE) and bias of treatment-effect and covariate estimates were collected. Standard errors (SE) and percentiles were used to compare estimate precision. Results Overall, IPD-NMA performed best in terms of validity and precision. The median MSE was lower in the IPD-NMA in 88 of 108 scenarios (similar results otherwise). On average, the IPD-NMA median MSE was 0.54 times the median using AgD-NMA-MR. Similarly, the SEs of the IPD-NMA treatment-effect estimates were 1/5 the size of AgD-NMA-MR SEs. The magnitude of superior validity and precision of using IPD-NMA varied across scenarios and was associated with the amount of IPD. Using IPD in small or sparse networks consistently led to improved validity and precision; however, in large/dense networks IPD tended to have negligible impact if too few IPD were included. Similar results also apply to the meta-regression coefficient estimates. Conclusions Our simulation study suggests that the use of IPD in NMA will considerably improve the validity and precision of estimates of treatment effect and regression coefficients in the most NMA IPD data-scenarios. However, IPD may not add meaningful validity and precision to NMAs of large and dense treatment networks when negligible IPD are used.

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