Screening for K13-Propeller Mutations Associated with Artemisinin Resistance in Plasmodium falciparum in Yambio County (Western Equatoria State, South Sudan)

Artemisinin-combined treatments are the recommended first-line treatment of Plasmodium falciparum malaria, but they are being threatened by emerging artemisinin resistance. Mutations in pfk13 are the principal molecular marker for artemisinin resistance. This study characterizes the presence of mutations in pfk13 in P. falciparum in Western Equatoria State, South Sudan. We analyzed 468 samples from patients with symptomatic malaria and found 15 mutations (8 nonsynonymous and 7 synonymous). Each mutation appeared only once, and none were validated or candidate markers of artemisinin resistance. However, some mutations were in the same or following position of validated and candidate resistance markers, suggesting instability of the gene that could lead to resistance. The R561L nonsynonymous mutation was found in the same position as the R561H validated mutation. Moreover, the A578S mutation, which is widespread in Africa, was also reported in this study. We found a high diversity of other pfk13 mutations in low frequency. Therefore, routine molecular surveillance of resistance markers is highly recommended to promptly detect the emergence of resistance-related mutations and to limit their spread.Financial support: The intervention was funded by Medecins Sans Frontieres, and samples were analyzed through a research agreement between Medecins Sans Frontieres and the National Centre of Tropical Medicine/Institute of Health Carlos III, Agreement No: TRVP 121/20. I. M. F. received a research fellowship (FPU-2019) from the University of Alcala, Spain, that enabled her to conduct this study.S

Escenarios de uso y efectividad de agentes hemostáticos

External hemorrhages derived from traumas caused by armed conflicts, road accidents and daily incidents are “increasingly frequent and represent 9% of annual mortality in the world, it is considered that hemorrhage is responsible for 30 to 40% of these deaths” (Mejia Mantilla, Puentes Manosalva, Ciro, & Morales, 2009). This encouraged the group of researchers to identify the scenarios of use and effectiveness of available hemostatic agents through a literature review; Key concepts in English and Spanish were taken into account for the search in databases, such as Pubmed, Lilacs, Scopus and Science Direct, in which methods, drugs, devices and pharmaceutical forms that are used for control were found. of hemorrhages. In a conglomerate and information processing, an analysis table was carried out in Microsoft Excel where 64 national and international documents on the use of hemostatic agents in the civil and military environment were included. These were classified according to their active ingredients, biomedical technology, mechanisms of action, hemostatic effects, material source, use scenarios, and effectiveness. It was concluded that defining the active ingredient based on the source of the material, for a future development of a hemostatic agent, will facilitate its availability and access, on the other hand, the education and training in the use of hemostatic agents and hemostatic biotechnological implementation, could influence the ease and access to them, these aspects could contribute to the reduction of morbidity and mortality in patients with external bleedingLas hemorragias externas derivadas de los traumas ocasionados por conflictos armados, accidentes viales e incidentes cotidianos son “cada vez más frecuentes y representan el 9% de la mortalidad anual en el mundo, se considera que la hemorragia es responsable del 30 al 40% de estas muertes” (Mejia Mantilla, Puentes Manosalva, Ciro, & Morales , 2009). Lo anterior incentivó al grupo de investigadores a identificar los escenarios de uso y efectividad de agentes hemostáticos disponibles mediante una revisión literaria; Se tomaron en cuenta conceptos claves en inglés y en español para la búsqueda en las bases de datos, tales como Pubmed, Lilacs, Scopus y Science Direct, en los que se hallaron métodos, medicamentos, dispositivos y formas farmacéuticas que son empleados para el control de las hemorragias. En un conglomerado y procesamiento de la información se llevó a cabo una tabla de análisis en Microsoft Excel donde se incluyeron 64 documentos tanto nacionales como internacionales del uso de agente hemostáticos en el entorno civil y militar. Estos fueron clasificados de acuerdo con sus ingredientes activos, tecnología biomédica, mecanismos de acción, efectos hemostáticos, fuente de material, escenarios de uso y efectividad. Se concluyó que definir el ingrediente activo en base a la fuente del material, para un desarrollo futuro de un agente hemostático facilitará su disponibilidad y el acceso, por otra parte la formación y capacitación en el uso de los agentes hemostáticos y la implementación biotecnológica hemostática, podría influir en la facilidad y el acceso a los mismos, estos aspectos podrían contribuir a la reducción la morbimortalidad en pacientes con hemorragias externa

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

New filovirus disease classification and nomenclature.

The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision

Plasmodium falciparum pfhrp2 and pfhrp3 Gene Deletions in Malaria-Hyperendemic Region, South Sudan

Pfhrp2 and pfhrp3 gene deletions threaten the use of Plasmodium falciparum malaria rapid diagnostic tests globally. In South Sudan, deletion frequencies were 15.6% for pfhrp2, 20.0% for pfhrp3, and 7.5% for double deletions. Deletions were approximately twice as prevalent in monoclonal infections than in polyclonal infections

Clinical profile and containment of the Ebola virus disease outbreak in two large West African cities, Nigeria, July–September 2014

Introduction: The Ebola virus disease (EVD) outbreak in Nigeria began when an infected diplomat from Liberia arrived in Lagos, the most populous city in Africa, with subsequent transmission to another large city. Methods: First-, second-, and third-generation contacts were traced, monitored, and classified. Symptomatic contacts were managed at Ebola treatment centers as suspected, probable, and confirmed EVD cases using standard operating procedures adapted from the World Health Organization EVD guidelines. Reverse transcription PCR tests confirmed EVD. Socio-demographic, clinical, hospitalization, and outcome data of the July–September 2014 Nigeria EVD cohort were analyzed. Results: The median age of the 20 EVD cases was 33 years (interquartile range 26–62 years). More females (55%), health workers (65%), and persons <40 years old (60%) were infected than males, non-health workers, and persons aged ≥40 years. No EVD case management worker contracted the disease. Presenting symptoms were fever (85%), fatigue (70%), and diarrhea (65%). Clinical syndromes were gastroenteritis (45%), hemorrhage (30%), and encephalopathy (15%). The case-fatality rate was 40% and there was one mental health complication. The average duration from symptom onset to presentation was 3 ± 2 days among survivors and 5 ± 2 days for non-survivors. The mean duration from symptom onset to discharge was 15 ± 5 days for survivors and 11 ± 2 days for non-survivors. Mortality was higher in the older age group, males, and those presenting late. Conclusion: The EVD outbreak in Nigeria was characterized by the severe febrile gastroenteritis syndrome typical of the West African outbreak, better outcomes, rapid containment, and no infection among EVD care-providers. Early case detection, an effective incident management system, and prompt case management with on-site mobilization and training of local professionals were key to the outcome

Dietary polyphenol intake is associated with HDL-cholesterol and a better profile of other components of the metabolic syndrome: a PREDIMED-Plus sub-study

Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvención con DIeta MEDiterranea-Plus) study. The polyphenol content of foods was estimated from the Phenol-Explorer 3.6 database. The mean of total polyphenol intake was 846 ± 318 mg/day. Except for stilbenes, women had higher polyphenol intake than men. Total polyphenol intake was higher in older participants (>70 years of age) compared to their younger counterparts. Participants with body mass index (BMI) >35 kg/m2 reported lower total polyphenol, flavonoid, and stilbene intake than those with lower BMI. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. To conclude, in participants with MetS, higher intake of several polyphenol subclasses was associated with a better profile of MetS components, especially HDL-c.The PREDIMED-Plus trial was supported by official Spanish institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (four coordinated FIS projects led by J.S.-S. and J.Vi., including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, and PI17/00926), the Special Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S., the Recercaixa grant to J.S.-S. (2013ACUP00194), a grant from the Fundació la Marató de TV3 (PI044003), grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018),grants from the Generalitat Valenciana (PROMETEO/2017/017, APOSTD/2019/136), a SEMERGEN grant, a CICYT grant provided by the Ministerio de Ciencia, Innovación y Universidades (AGL2016-75329-R) and funds from the European Regional Development Fund (CB06/03). The Spanish Ministry of Science Innovation and Universities for the Formación de Profesorado Universitario (FPU17/00785) contract. Food companies Hojiblanca (Lucena, Spain) and Patrimonio Comunal Olivarero (Madrid, Spain) donated extra virgin olive oil, and the Almond Board of California (Modesto, CA), American Pistachio Growers (Fresno, CA), and Paramount Farms (Wonderful Company, LLC, Los Angeles, CA) donated nuts. This call is co-financed at 50% with charge to the Operational Program FSE 2014-2020 of the Balearic Islands