Molecular markers and allelic relationships of anthracnose resistance gene cluster B4 in common bean

Allelism tests and molecular marker analyses were combined to characterize the genes that, proceeding from the germplasm lines ‘A493’ and ‘A321’, confer resistance to bean anthracnose in the new breeding lines ‘A1220’ and ‘A1231’, respectively, developed through backcross breeding, using the dry bean landrace ‘Andecha’ as the recurrent parent. Allelism tests indicate that resistance to race 38 of anthracnose in genotypes ‘A1220’, ‘A1231’, and ‘BAT 93’ and in the differential cultivars ‘PI 207262’ and ‘Mexico 222’ is determined by different dominant alleles at the same locus. Therefore, the results obtained suggest that the so far considered as different genes Co-3 (described as present in ‘Mexico 222’) and Co-9 (described as present in ‘BAT 93’) are alleles of the same gene. RAPD markers OB12350, OAH181100, and OY171100 and SCAR markers SI19 and SW12 were found to be linked to the resistance gene. Data indicate that the resistance genes to race 38 present in these materials are alleles of the same R gene cluster located in linkage group B4, because markers OY171100, SI19 and SW12 were previously linked to this cluster. The SCAR markers SB12 and SAH18 were developed from RAPDs OB12350 and OAH181100, respectively, and a genetic map including the resistance gene and markers SB12, OY171100, SAH18, SW12 and SI19 was made using a F2 segregating population of 72 individuals derived from the cross ‘Andecha’ × ‘A493’

Weakly-supervised detection of AMD-related lesions in color fundus images using explainable deep learning

[Abstract]: Background and Objectives: Age-related macular degeneration (AMD) is a degenerative disorder affecting the macula, a key area of the retina for visual acuity. Nowadays, AMD is the most frequent cause of blindness in developed countries. Although some promising treatments have been proposed that effectively slow down its development, their effectiveness significantly diminishes in the advanced stages. This emphasizes the importance of large-scale screening programs for early detection. Nevertheless, implementing such programs for a disease like AMD is usually unfeasible, since the population at risk is large and the diagnosis is challenging. For the characterization of the disease, clinicians have to identify and localize certain retinal lesions. All this motivates the development of automatic diagnostic methods. In this sense, several works have achieved highly positive results for AMD detection using convolutional neural networks (CNNs). However, none of them incorporates explainability mechanisms linking the diagnosis to its related lesions to help clinicians to better understand the decisions of the models. This is specially relevant, since the absence of such mechanisms limits the application of automatic methods in the clinical practice. In that regard, we propose an explainable deep learning approach for the diagnosis of AMD via the joint identification of its associated retinal lesions. Methods: In our proposal, a CNN with a custom architectural setting is trained end-to-end for the joint identification of AMD and its associated retinal lesions. With the proposed setting, the lesion identification is directly derived from independent lesion activation maps; then, the diagnosis is obtained from the identified lesions. The training is performed end-to-end using image-level labels. Thus, lesion-specific activation maps are learned in a weakly-supervised manner. The provided lesion information is of high clinical interest, as it allows clinicians to assess the developmental stage of the disease. Additionally, the proposed approach allows to explain the diagnosis obtained by the models directly from the identified lesions and their corresponding activation maps. The training data necessary for the approach can be obtained without much extra work on the part of clinicians, since the lesion information is habitually present in medical records. This is an important advantage over other methods, including fully-supervised lesion segmentation methods, which require pixel-level labels whose acquisition is arduous. Results: The experiments conducted in 4 different datasets demonstrate that the proposed approach is able to identify AMD and its associated lesions with satisfactory performance. Moreover, the evaluation of the lesion activation maps shows that the models trained using the proposed approach are able to identify the pathological areas within the image and, in most cases, to correctly determine to which lesion they correspond. Conclusions: The proposed approach provides meaningful information—lesion identification and lesion activation maps—that conveniently explains and complements the diagnosis, and is of particular interest to clinicians for the diagnostic process. Moreover, the data needed to train the networks using the proposed approach is commonly easy to obtain, what represents an important advantage in fields with particularly scarce data, such as medical imaging.Xunta de Galicia; ED481B-2022-025Xunta de Galicia; ED431C 2020/24Xunta de Galicia; IN845D 2020/38Xunta de Galicia; ED481A 2021/140Xunta de Galicia; ED431G 2019/01This work was funded by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project; Ministerio de Ciencia e Innovación, Government of Spain, through RTI2018-095894-B-I00 and PID2019-108435RB-I00 research projects; Axencia Galega de Innovación (GAIN), Xunta de Galicia, ref. IN845D 2020/38; Conselleria de Cultura, Educación e Universidade, Xunta de Galicia, through Grupos de Referencia Competitiva, ref. ED431C 2020/24, the predoctoral grant ref. ED481A 2021/140, and the postdoctoral grant ref. ED481B-2022-025; CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, is funded by Conselleria de Educación, Universidade e Formación Profesional, Xunta de Galicia, through the ERDF (80%) and Secretaria Xeral de Universidades (20%)

Recommendations for ophthalmologic practice during the easing of COVID-19 control measures

In the context of the COVID-19 pandemic, this paper provides recommendations for medical eye care during the easing of control measures after lockdown. The guidelines presented are based on a literature review and consensus among all Spanish Ophthalmology Societies regarding protection measures recommended for the ophthalmologic care of patients with or without confirmed COVID-19 in outpatient, inpatient, emergency and surgery settings. We recommend that all measures be adapted to the circumstances and availability of personal protective equipment at each centre and also highlight the need to periodically update recommendations as we may need to readopt more restrictive measures depending on the local epidemiology of the virus. These guidelines are designed to avoid the transmission of SARS-CoV-2 among both patients and healthcare staff as we gradually return to normal medical practice, to prevent postoperative complications and try to reduce possible deficiencies in the diagnosis, treatment and follow-up of the ophthalmic diseases. With this update (5th) the Spanish Society of Ophthalmology is placed as one of the major ophthalmology societies providing periodic and systematized recommendations for ophthalmic care during the COVID-19 pandemic

Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study

Background: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability.Aims: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome.Methods: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed.Results: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300 mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24 h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality.Conclusions: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE

Patterns of care and dropout rates from outpatient mental healthcare in low-, middle- and high-income countries from the World Health Organization’s World Mental Health Survey Initiative

Background:There is a substantial proportion of patients who drop out of treatment beforethey receive minimally adequate care. They tend to have worse health outcomes than thosewho complete treatment. Our main goal is to describe the frequency and determinants ofdropout from treatment for mental disorders in low-, middle-, and high-income countries.Methods: Respondents from 13 low- or middle-income countries (N= 60 224) and 15 in high-income countries (N= 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for thosewho screened positive. The timing of dropout was examined using Kaplan–Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function. Results: Dropout rates are high, both in high-income (30%) and low/middle-income (45%)countries. Dropout mostly occurs during the first two visits. It is higher in general medicalrather than in specialist settings (nearly 60%v.20% in lower income settings). It is also higherfor mild and moderate than for severe presentations. The lack of financial protection for men-tal health services is associated with overall increased dropout from care.Conclusions:Extending financial protection and coverage for mental disorders may reducedropout. Efficiency can be improved by managing the milder clinical presentations at theentry point to the mental health system, providing adequate training, support and specialistsupervision for non-specialists, and streamlining referral to psychiatrists for more severe casesPeer ReviewedPostprint (author's final draft

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Anales del III Congreso Internacional de Vivienda y Ciudad "Debate en torno a la nueva agenda urbana"

Acta de congresoEl III Congreso Internacional de Vivienda y Ciudad “Debates en torno a la NUEVa Agenda Urbana”, ha sido una apuesta de alto compromiso por acercar los debates centrales y urgentes que tensionan el pleno ejercicio del derecho a la ciudad. Para ello las instituciones organizadoras (INVIHAB –Instituto de Investigación de Vivienda y Hábitat y MGyDH-Maestría en Gestión y Desarrollo Habitacional-1), hemos convidado un espacio que se concretó con potencia en un debate transdisciplinario. Convocó a intelectuales de prestigio internacional, investigadores, académicos y gestores estatales, y en una metodología de innovación articuló las voces académicas con las de las organizaciones sociales y/o barriales en el Foro de las Organizaciones Sociales que tuvo su espacio propio para dar voz a quienes están trabajando en los desafíos para garantizar los derechos a la vivienda y los bienes urbanos en nuestras ciudades del Siglo XXI

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues