Genomic prediction and training set optimization in a structured Mediterranean oat population.

KEY MESSAGE: The strong genetic structure observed in Mediterranean oats affects the predictive ability of genomic prediction as well as the performance of training set optimization methods. In this study, we investigated the efficiency of genomic prediction and training set optimization in a highly structured population of cultivars and landraces of cultivated oat (Avena sativa) from the Mediterranean basin, including white (subsp. sativa) and red (subsp. byzantina) oats, genotyped using genotype-by-sequencing markers and evaluated for agronomic traits in Southern Spain. For most traits, the predictive abilities were moderate to high with little differences between models, except for biomass for which Bayes-B showed a substantial gain compared to other models. The consistency between the structure of the training population and the population to be predicted was key to the predictive ability of genomic predictions. The predictive ability of inter-subspecies predictions was indeed much lower than that of intra-subspecies predictions for all traits. Regarding training set optimization, the linear mixed model optimization criteria (prediction error variance (PEVmean) and coefficient of determination (CDmean)) performed better than the heuristic approach "partitioning around medoids," even under high population structure. The superiority of CDmean and PEVmean could be explained by their ability to adapt the representation of each genetic group according to those represented in the population to be predicted. These results represent an important step towards the implementation of genomic prediction in oat breeding programs and address important issues faced by the genomic prediction community regarding population structure and training set optimization.

Enhancing the sustainability and climate resiliency of health care facilities: a comparison of initiatives and toolkits.

Extreme weather events have revealed the vulnerability of health care facilities and the extent of devastation to the community when they fail. With climate change anticipated to increase extreme weather and its impacts worldwide-severe droughts, floods, heat waves, and related vector-borne diseases-health care officials need to understand and address the vulnerabilities of their health care systems and take action to improve resiliency in ways that also meet sustainability goals. Generally, the health sector is among a country's largest consumers of energy and a significant source of greenhouse gas emissions. Now it has the opportunity lead climate mitigation, while reducing energy, water, and other costs. This Special Report summarizes several initiatives and compares three toolkits for implementing sustainability and resiliency measures for health care facilities: the Canadian Health Care Facility Climate Change Resiliency Toolkit, the U.S. Sustainable and Climate Resilient Health Care Facilities Toolkit, and the PAHO SMART Hospitals Toolkit of the World Health Organization/Pan American Health Organization. These tools and the lessons learned can provide a critical starting point for any health system in the Americas.

BTH and BABA induce resistance in pea against rust (Uromyces pisi) involving differential phytoalexin accumulation.

MAIN CONCLUSION: Systemic acquired resistance elicitors, BTH and BABA, reduce rust penetration in pea through phytoalexins pathway but differing in their mode of action. It has been previously shown that rust (Uromyces pisi) infection can be reduced in pea (Pisum sativum) by exogenous applications of systemic acquired resistance elicitors such as BTH and BABA. This protection is known to be related with the induction of the phenolic pathway but the particular metabolites involved have not been determined yet. In this work, we tackled the changes induced in phytoalexin content by BTH and BABA treatments in the context of the resistance responses to pea rust. Detailed analysis through high-performance liquid chromatography (HPLC) showed qualitative and quantitative differences in the content, as well as in the distribution of phytoalexins. Thus, following BTH treatment, we observed an increase in scopoletin, pisatin and medicarpin contents in all, excreted, soluble and cell wall-bound fraction. This suggests fungal growth impairment by both direct toxic effect as well as plant cell wall reinforcement. The response mediated by BTH was genotype-dependent, since coumarin accumulation was observed only in the resistant genotype whereas treatment by BABA primed phytoalexin accumulation in both genotypes equally. Exogenous application to the leaves of scopoletin, medicarpin and pisatin lead to a reduction of the different fungal growth stages, confirming a role for these phytoalexins in BTH- and BABA-induced resistance against U. pisi hampering pre- and postpenetration fungal stages.

A metabolomic study in oats (Avena sativa) highlights a drought tolerance mechanism based upon salicylate signalling pathways and the modulation of carbon, antioxidant and photo-oxidative metabolism.

Although a wealth of information is available on the induction of one or several drought-related responses in different species, little is known of how their timing, modulation and crucially integration influence drought tolerance. Based upon metabolomic changes in oat (Avena sativa L.), we have defined key processes involved in drought tolerance. During a time course of increasing water deficit, metabolites from leaf samples were profiled using direct infusion-electrospray mass spectroscopy (DI-ESI-MS) and high-performance liquid chromatography (HPLC) ESI-MS/MS and analysed using principal component analysis (PCA) and discriminant function analysis (DFA). The involvement of metabolite pathways was confirmed through targeted assays of key metabolites and physiological experiments. We demonstrate an early accumulation of salicylic acid (SA) influencing stomatal opening, photorespiration and antioxidant defences before any change in the relative water content. These changes are likely to maintain plant water status, with any photoinhibitory effect being counteracted by an efficient antioxidant capacity, thereby representing an integrated mechanism of drought tolerance in oats. We also discuss these changes in relation to those engaged at later points, consequence of the different water status in susceptible and resistant genotypes.

Long-term remission with rituximab in a patient with severe hepatitis C virus-induced mixed cryoglobulinemia.

Mixed cryoglobulinemia (MC) is a small-vessel systemic vasculitis characterized by the presence of cryoglobulins, immunoglobulin complexes that precipitate at low temperatures ( < 37 ºC) inducing the inflammatory process. The most frequent etiology is hepatitis C infection (HCV) (1). Rituximab (RTX), an anti-CD20 monoclonal antibody, has recently emerged as the treatment of choice for severe MC (2). We present a case of severe hepatitis C virus-induced MC that was controlled and maintained in remission with RTX for 26 months, a remarkable prolonged period of time.

Epidemiology of Fabry disease in patients in hemodialysis in the Madrid community.

This study screened for Fabry disease (FD) in patients in hemodialysis (HD) in the region of Madrid (CAM) with a cross-sectional design to evaluate HD-prevalent patients, followed by a three-year period prospective design to analyze HD-incident patients. INCLUSION CRITERIA: patients older than 18 years on HD in the CAM, excluding patients diagnosed with any other hereditary disease with renal involvement different from FD, that sign the Informed Consent (IC). EXCLUSION CRITERIA: underaged patients or not agreeing or not being capable of signing the IC. RESULTS: 3470 patients were included, 63% males and with an average age of 67.9±9.7 years. 2357 were HD-prevalent patients and 1113 HD-incident patients. For HD-prevalent patients, average time in HD was 45.2 months (SD 51.3), in HD-incident patients proteinuria was present in 28.4%. There were no statistical differences in plasmatic alpha-galactosidase A (α-GAL-A) activity or Lyso-GL-3 values when comparing HD-prevalent and HD-incident populations and neither between males and females. A genetic study was performed in 87 patients (2.5% of patients): 60 male patients with decreased enzymatic activity and 27 female patients either with a decreased GLA activity, increased Lyso-Gl3 levels or both. The genetic variants identified were: p.Asp313Tyr (4 patients), p.Arg220Gln (3 patients) and M290I (1 patient). None of the identified variants is pathogenic. CONCLUSIONS: 76% of HD Centers of the CAM participated in the study. This is the first publication to describe the prevalence of FD in the HD-population of a region of Spain as well as its average α-GAL-A-activity and plasmatic Lyso-Gl3 levels. It is also the first study that combines a cross-sectional design with a prospective follow-up design. This study has not identified any FD patient.

Targeting sources of drought tolerance within an Avena spp. collection through multivariate approaches.

In this study, we find and characterize the sources of tolerance to drought amongst an oat (Avena sativa L.) germplasm collection of 174 landraces and cultivars. We used multivariate analysis, non-supervised principal component analyses (PCA) and supervised discriminant function analyses (DFA) to suggest the key mechanism/s responsible for coping with drought stress. Following initial assessment of drought symptoms and area under the drought progress curve, a subset of 14 accessions were selected for further analysis. The collection was assessed for relative water content (RWC), cell membrane stability, stomatal conductance (g (1)), leaf temperature, water use efficiency (WUE), lipid peroxidation, lipoxygenase activity, chlorophyll levels and antioxidant capacity during a drought time course experiment. Without the use of multivariate approaches, it proved difficult to unequivocally link drought tolerance to specific physiological processes in the different resistant oat accessions. These approaches allowed the ranking of many supposed drought tolerance traits in the order of degree of importance within this crop, thereby highlighting those with a causal relationship to drought stress tolerance. Analyses of the loading vectors used to derive the PCA and DFA models indicated that two traits involved in water relations, temperature and RWC together with the area of drought curves, were important indicators of drought tolerance. However, other parameters involved in water use such as g (1) and WUE were less able to discriminate between the accessions. These observations validate our approach which should be seen as representing a cost-effective initial screen that could be subsequently employed to target drought tolerance in segregating populations.

Mental health and the global climate crisis.

AIMS: Not only is nature essential for human existence, but many of its functions and contributions are irreplaceable. Studying the impact of these changes on individuals and communities, researchers and public health officials have largely focused on physical health. Our aim is to better understand how climate change also exacerbates many social and environmental risk factors for mental health and psychosocial problems, and can lead to emotional distress, the development of new mental health conditions and a worsening situation for people already living with these conditions. METHODS: We considered all possible direct and indirect pathways by which climate change can affect mental health. We built a framework which includes climate change-related hazards, climate change-related global environmental threats, social and environmental exposure pathways, and vulnerability factors and inequalities to derive possible mental health and psychosocial outcomes. RESULTS: We identified five approaches to address the mental health and psychosocial impacts of climate change which we suggest should be implemented with urgency: (1) integrate climate change considerations into policies and programmes for mental health, to better prepare for and respond to the climate crisis; (2) integrate mental health and psychosocial support within policies and programmes dealing with climate change and health; (3) build upon global commitments including the Sustainable Development Goals, the Paris Agreement and the Sendai Framework for Disaster Risk Reduction; (4) implement multisectoral and community-based approaches to reduce vulnerabilities and address the mental health and psychosocial impacts of climate change; and (5) address the large gaps that exist in funding both for mental health and for responding to the health impacts of climate change. CONCLUSIONS: There is growing evidence of the various mechanisms by which climate change is affecting mental health. Given the human impacts of climate change, mental health and psychosocial well-being need to be one of the main focuses of climate action. Therefore, countries need to dramatically accelerate their responses to climate change, including efforts to address its impacts on mental health and psychosocial well-being.

More difficult still: Treating severe rapidly progressive glomerulonephritis in the context of COVID-19 pneumonia.

We present the case of a male patient with severe SARS-CoV-2 pneumonia, with simultaneous onset of p-ANCA positive rapidly progressive glomerulonephritis. We discuss the different therapeutic possibilities, emphasising the appropriateness of their administration according to the time in the course of the infection.

Infrastructure alone cannot ensure resilience to weather events in drinking water supplies.

Climate resilient water supplies are those that provide access to drinking water that is sustained through seasons and through extreme events, and where good water quality is also sustained. While surface and groundwater quality are widely understood to vary with rainfall, there is a gap in the evidence on the impact of weather and extremes in rainfall and temperature on drinking water quality, and the role of changes in water system management. A three-country (Bangladesh, Nepal and Tanzania) observational field study tracked 2353 households clustered around 685 water sources across seven different geographies over 14 months. Water quality (E. coli) data was modelled using GEE to account for clustering effects and repeated measures at households. All types of infrastructure were vulnerable to changes in weather, with differences varying between geographies; protected boreholes provided the greatest protection at the point of collection (PoC). Water quality at the point of use (PoU) was vulnerable to changes in weather, through changes in PoC water quality as well as changes in management behaviours, such as safe storage, treatment and cleaning. This is the first study to demonstrate the impact of rainfall and temperature extremes on water quality at the PoC, and the role that weather has on PoU water quality via management behaviours. Climate resilience for water supplies needs to consider the infrastructure as well as the management decisions that are taking place at a community and household level.

Deciphering Main Climate and Edaphic Components Driving Oat Adaptation to Mediterranean Environments.

Oat, Avena sativa, is an important crop traditionally grown in cool-temperate regions. However, its cultivated area in the Mediterranean rim steadily increased during the last 20 years due to its good adaptation to a wide range of soils. Nevertheless, under Mediterranean cultivation conditions, oats have to face high temperatures and drought episodes that reduce its yield as compared with northern regions. Therefore, oat crop needs to be improved for adaptation to Mediterranean environments. In this work, we investigated the influence of climatic and edaphic variables on a collection of 709 Mediterranean landraces and cultivars growing under Mediterranean conditions. We performed genotype-environment interaction analysis using heritability-adjusted genotype plus genotype-environment biplot analyses to determine the best performing accessions. Further, their local adaptation to different environmental variables and the partial contribution of climate and edaphic factors to the different agronomic traits was determined through canonical correspondence, redundancy analysis, and variation partitioning. Here, we show that northern bred elite cultivars were not among the best performing accessions in Mediterranean environments, with several landraces outyielding these. While all the best performing cultivars had early flowering, this was not the case for all the best performing landraces, which showed different patterns of adaption to Mediterranean agroclimatic conditions. Thus, higher yielding landraces showed adaptation to moderate to low levels of rain during pre- and post-flowering periods and moderate to high temperature and radiation during post-flowering period. This analysis also highlights landraces adapted to more extreme environmental conditions. The study allowed the selection of oat genotypes adapted to different climate and edaphic factors, reducing undesired effect of environmental variables on agronomic traits and highlights the usefulness of variation partitioning for selecting genotypes adapted to specific climate and edaphic conditions.

More difficult still: Treating severe rapidly progressive glomerulonephritis in the context of COVID-19 pneumonia. / Más difícil todavía: tratar una glomerulonefritis rápidamente progresiva grave en el seno de una neumonía por COVID-19.

We present the case of a male patient with severe SARS-CoV-2 pneumonia, with simultaneous onset of p-ANCA positive rapidly progressive glomerulonephritis. We discuss the different therapeutic possibilities, emphasising the appropriateness of their administration according to the time in the course of the infection.

Diagnostic Accuracy and Detection Rate of Glaucoma Screening with Optic Disk Photos, Optical Coherence Tomography Images, and Telemedicine.

PURPOSE: The aim of this study was to evaluate the diagnostic accuracy of optical coherence tomography (OCT) and retinography in the detection of glaucoma through a telemedicine program. METHODS: A population-based sample of 4113 persons was randomly selected. The screening examination included a fundus photograph and OCT images. Images were evaluated on a deferred basis. All participants were then invited to a complete glaucoma examination, including gonioscopy, visual field, and dilated fundus examination. The detection rate, sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: We screened 1006 persons. Of these, 201 (19.9%) were classified as glaucoma suspects; 20.4% were identified only by retinographs, 11.9% only by OCT images, and 46.3% by both. On ophthalmic examination at the hospital (n = 481), confirmed glaucoma was found in 58 (12.1%), probable glaucoma in 76 (15.8%), and ocular hypertension in 10 (2.1%), and no evidence of glaucoma was found in 337 (70.0%). The detection rate for confirmed or probable glaucoma was 9.2%. Sensitivity ranged from 69.4% to 86.2% and specificity from 82.1% to 97.4%, depending on the definition applied. CONCLUSIONS: The combination of OCT images and fundus photographs yielded a detection rate of 9.2% in a population-based screening program with moderate sensitivity, high specificity, and predictive values of 84-96%.

Interobserver and Intertest Agreement in Telemedicine Glaucoma Screening with Optic Disk Photos and Optical Coherence Tomography.

Purpose: To evaluate interobserver and intertest agreement between optical coherence tomography (OCT) and retinography in the detection of glaucoma through a telemedicine program. Methods: A stratified sample of 4113 individuals was randomly selected, and those who accepted underwent examination including visual acuity, intraocular pressure (IOP), non-mydriatic retinography, and imaging using a portable OCT device. Participants' data and images were uploaded and assessed by 16 ophthalmologists on a deferred basis. Two independent evaluations were performed for all participants. Agreement between methods was assessed using the kappa coefficient and the prevalence-adjusted bias-adjusted kappa (PABAK). We analyzed potential factors possibly influencing the level of agreement. Results: The final sample comprised 1006 participants. Of all suspected glaucoma cases (n = 201), 20.4% were identified in retinographs only, 11.9% in OCT images only, 46.3% in both, and 21.4% were diagnosed based on other data. Overall interobserver agreement outcomes were moderate to good with a kappa coefficient of 0.37 and a PABAK index of 0.58. Higher values were obtained by experienced evaluators (kappa = 0.61; PABAK = 0.82). Kappa and PABAK values between OCT and photographs were 0.52 and 0.82 for the first evaluation. Conclusion: In a telemedicine screening setting, interobserver agreement on diagnosis was moderate but improved with greater evaluator expertise.

Proteomics of plant pathogenic fungi.

Plant pathogenic fungi cause important yield losses in crops. In order to develop efficient and environmental friendly crop protection strategies, molecular studies of the fungal biological cycle, virulence factors, and interaction with its host are necessary. For that reason, several approaches have been performed using both classical genetic, cell biology, and biochemistry and the modern, holistic, and high-throughput, omic techniques. This work briefly overviews the tools available for studying Plant Pathogenic Fungi and is amply focused on MS-based Proteomics analysis, based on original papers published up to December 2009. At a methodological level, different steps in a proteomic workflow experiment are discussed. Separate sections are devoted to fungal descriptive (intracellular, subcellular, extracellular) and differential expression proteomics and interactomics. From the work published we can conclude that Proteomics, in combination with other techniques, constitutes a powerful tool for providing important information about pathogenicity and virulence factors, thus opening up new possibilities for crop disease diagnosis and crop protection.

Blumeria graminis interactions with barley conditioned by different single R genes demonstrate a temporal and spatial relationship between stomatal dysfunction and cell death.

Hypersensitive response (HR) against Blumeria graminis f. sp. hordei infection in barley (Hordeum vulgare) was associated with stomata "lock-up" leading to increased leaf water conductance (g(l)). Unique spatio-temporal patterns of HR formation occurred in barley with Mla1, Mla3, or MlLa R genes challenged with B. graminis f. sp. hordei. With Mla1, a rapid HR, limited to epidermal cells, arrested fungal growth before colonies initiated secondary attacks. With Mla3, mesophyll HR preceded that in epidermal cells whose initial survival supported secondary infections. With MlLa, mesophyll survived and not all attacked epidermal cells died immediately, allowing colony growth and secondary infection until arrested. Isolines with Mla1, Mla3, or MlLa genes inoculated with B. graminis f. sp. hordei ranging from 1 to 100 conidia mm(2) showed abnormally high g(l) during dark periods whose timing and extent correlated with those of each HR. Each isoline showed increased dark g(l) with the nonpathogen B. graminis f. sp. avenae which caused a single epidermal cell HR. Guard cell autofluorescence was seen only after drying of epidermal strips and closure of stomata suggesting that locked open stomata were viable. The data link stomatal lock-up to HR associated cell death and has implications for strategies for selecting disease resistant genotypes.

RUST: A Robust, User-Friendly Script Tool for Rapid Measurement of Rust Disease on Cereal Leaves.

Recently, phenotyping has become one of the main bottlenecks in plant breeding and fundamental plant science. This is particularly true for plant disease assessment, which has to deal with time-consuming evaluations and the subjectivity of visual assessments. In this work, we have developed an open source Robust, User-friendy Script Tool (RUST) for semi-automated evaluation of leaf rust diseases. RUST runs under the free Fiji imaging software (developed from ImageJ), which is a well-recognized software among the scientific community. The script enables the evaluation of leaf rust diseases using a color transformation tool and provides three different automation modes. The script opens images sequentially and records infection frequency (pustules per area) (semi-)automatically for high-throughput analysis. Furthermore, it can manage several scanned leaf segments in the same image, consecutively selecting the desired segments. The script has been validated with nearly 900 samples from 80 oat genotypes ranging from resistant to susceptible and from very light to heavily infected leaves showing a high accuracy with a Lin's concordance correlation coefficient of 0.99. The analysis show a high repeatability as indicated by the low variation coefficients obtained when repeating the measurement of the same samples. The script also has optional steps for calibration and training to ensure accuracy, even in low-resolution images. This script can evaluate efficiently hundreds of leaves facilitating the screening of novel sources of resistance to this important cereal disease.

Immunosuppression as a trigger for hyperinflammatory syndrome due to Strongyloides stercolaris in membranous nephropathy. / Inmunosupresión como desencadenante de un síndrome de hiperinfestación por Strongyloides stercolaris en la nefropatía membranosa.

The relationship between parasites and glomerulonephritis (GN) is well documented in certain parasitoses, but not in cases of Strongyloides stercolaris (S. stercolaris) where there are few cases described being the majority GN of minimal changes. We report a case of hyperinfestation by S. stercolaris in a patient affected by a membranous GN treated with oral corticosteroids with fatal outcome for the patient. This case provides a double teaching: first about a rare association of strongyloid and membranous GN and second about the importance of establishing a diagnosis of suspected and appropriate treatment for certain infections or diseases with little clinical expression before starting any immunosuppressive treatment.

Towards Climate Resilient and Environmentally Sustainable Health Care Facilities.

The aim of building climate resilient and environmentally sustainable health care facilities is: (a) to enhance their capacity to protect and improve the health of their target communities in an unstable and changing climate; and (b) to empower them to optimize the use of resources and minimize the release of pollutants and waste into the environment. Such health care facilities contribute to high quality of care and accessibility of services and, by helping reduce facility costs, also ensure better affordability. They are an important component of universal health coverage. Action is needed in at least four areas which are fundamental requirements for providing safe and quality care: having adequate numbers of skilled human resources, with decent working conditions, empowered and informed to respond to these environmental challenges; sustainable and safe management of water, sanitation and health care waste; sustainable energy services; and appropriate infrastructure and technologies, including all the operations that allow for the efficient functioning of a health care facility. Importantly, this work contributes to promoting actions to ensure that health care facilities are constantly and increasingly strengthened and continue to be efficient and responsive to improve health and contribute to reducing inequities and vulnerability within their local settings. To this end, we propose a framework to respond to these challenges.

Characterization of resistance mechanisms to powdery mildew (Erysiphe betae) in beet (Beta vulgaris).

Beet powdery mildew incited by Erysiphe betae is a serious foliar fungal disease of worldwide distribution causing losses of up to 30%. In the present work, we searched for resistance in a germplasm collection of 184 genotypes of Beta vulgaris including fodder (51 genotypes), garden (60 genotypes), leaf (51 genotypes), and sugar (22 genotypes) beet types. Resistant genotypes were identified in the four beet types under study. In addition, mechanisms underlying resistance were dissected through histological studies. These revealed different resistance mechanisms acting at different fungal developmental stages, i.e., penetration resistance, early and late cell death, or posthaustorial resistance. Most genotypes were able to hamper fungal development at several stages. The later are interesting for breeding aiming to resistance durability. Furthermore, characterization of defense mechanisms will be useful for further cellular and molecular studies to unravel the bases of resistance in this species.