Controllable production of Janus ligaments by AC fields in a flow-focusing junction

We report the production of bicomponent Janus filaments of miscible aqueous fluids in a micro- fluidic electro-flow focusing device under the action of an AC electric field. The production of liquid filaments can lead to the generation of microfibers by adding a subsequent process of polymerization. Janus microfi- bers are of paramount importance in biomedical appli- cations such as tissue production on crimped scaffolds. We show that the filament length is a function of the frequency signal, voltage amplitude and of the visco- sity and conductivity of the dispersed phase. In par- ticular, Janus filaments with diameters ∼ 10μm and longer than 1 mm are produced by AC voltages with frequencies below 150 kHz and a viscosity of the dis- persed phase ∼ 10 cP

The LINCE Project: A Pathway for Diagnosing NCL2 Disease

NCL2 disease; Dried blood spot; Enzymatic activityEnfermedad de NCL2; Mancha de sangre seca; Actividad enzimáticaMalaltia de NCL2; Taca de sang seca; Activitat enzimàticaIntroduction: Neuronal Ceroid Lipofuscinosis (NCL) comprises a clinically and genetically heterogeneous group of 13 neurodegenerative lysosomal storage disorders. Neuronal Ceroid lipofuscinosis type 2 disease (NCL2), caused by the deficient lysosomal enzyme tripeptidyl peptidase 1 (TPP1), is the only one with an approved enzyme replacement treatment (ERT). Early initiation of ERT appears to modify significantly the natural history of the disease. We aimed to shorten the time to diagnosis of NCL2. Methods: In March 2017, we started per first time in Spain a selective screening program, the LINCE project, in pediatric patients with clinical symptoms compatible with NCL2 disease. The program covered the whole country. We distributed kits to pediatricians with the necessary material to assess patients. All samples in this study were received within one week of collection. Enzymatic activity determined on dried blood spots was the main method used to screen for TPP1 and palmitoyl protein thioesterase 1 (PPT1) for the differential diagnosis with neuronal ceroid lipofuscinosis type 1 (NCL1). Results: Over a period of three years, we received 71 samples. The analysis was minimally invasive, relatively cheap and fast-executing. Three cases identified as a direct result of the selective screening strategy were confirmed by genetic study of NCL2 disease with a median age of 4.5 years. Our screening method has a specificity of 100%, and, with the absence to date of false negatives. We did not detect any NCL1-positive cases. Conclusions: LINCE proved to be a simple, useful, and reliable tool for the diagnosis of NCL2, enabling clinicians to diagnose NCL2 faster. The presence of NCL2-positive cases in our population and availability of treatment may facilitate the inclusion of NCL2 in neonatal screening programs for early diagnosis.This study received funding from Grant Biomarin Inc. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication

Specialized nutritious food combined with cash transfers and social and behavior change communication to prevent stunting among children aged 6 to 23 months in Pakistan: Protocol for a cluster randomized controlled trial

Background: In Pakistan, the prevalence of stunting in children younger than 5 years has remained above global critical levels over the past two decades, with the stunting rate being 40.2% in 2018. Children living in rural areas and in the poorest households suffer the most from stunting across the country-43.2% in rural areas and 51.4% in the lowest wealth quintile. As a continuing public health concern, it is essential that stunting prevention is a national priority in order to ensure human capital development, especially among the poorest households.Objective: The primary objective of this study is to determine the effect of a medium quantity of a lipid-based nutrient supplement (LNS) combined with unconditional cash transfers and social and behavior change communication (SBCC) on reduction of stunting in children aged 6 to 23 months.Methods: A 5-arm cluster randomized controlled trial will be conducted in the district of Rahim Yar Khan in Punjab, Pakistan. The intervention packages will be (1) cash only, (2) cash with LNS, (3) cash with SBCC, and (4) cash with SBCC and LNS. The control arm will receive routine standard of care. We will enroll children at 6 months of age and follow up on a monthly basis up to 24 months of age. A total of 2000 children, 400 in each arm, will be enrolled to detect a 20% reduction in the prevalence of stunting among children aged 24 months. Length, weight, food intake, compliance to interventions, morbidities, and other relevant data will be collected at enrollment and on a monthly basis over the period of 18 months. The process evaluation will assess acceptability of the interventions and potential barriers to implementation through focus group discussions and in-depth interviews with the target population and relevant stakeholders. Furthermore, a cost analysis will be conducted to assess the cost-effectiveness of each intervention package.Results: The study protocol was approved by the Ethics Review Committee of Aga Khan University in Pakistan on January 4, 2017. Data collection began in May 2017 and was completed in July 2019. Data analyses are yet to be completed. This study will explore the effectiveness of intervention packages comprised of cash transfers from Benazir Income Support Programme with or without additional LNS and SBCC in preventing childhood stunting. We expect the results to be published in peer-reviewed journals by autumn of 2020.Conclusions: The findings of this trial will provide robust evidence as to which intervention packages can have significant effects on linear growth of children and design effective intervention packages to prevent stunting in children aged 6 to 23 months

Hollow Gold Nanoparticles Produced by Femtosecond Laser Irradiation

[EN] Metallic hollow nanoparticles exhibit interesting optical properties that can be controlled by geometrical parameters. Irradiation with femtosecond laser pulses has emerged recently as a valuable tool for reshaping and size modification of plasmonic metal nanoparticles, thereby enabling the synthesis of nanostructures with unique morphologies. In this Letter, we use classical molecular dynamics simulations to investigate the solid-to-hollow conversion of gold nanoparticles upon femtosecond laser irradiation. Here, we suggest an efficient method for producing hollow nanoparticles under certain specific conditions, namely that the particles should be heated to a maximum temperature between 2500 and 3500 K, followed by a fast quenching to room temperature, with cooling rates lower than 120 ps. Therefore, we describe the experimental conditions for efficiently producing hollow nanoparticles, opening a broad range of possibilities for applications in key areas, such as energy storage and catalysis.This work has been funded by the Spanish Ministry of Science, Innovation and Universities (MICIU) (Grants RTI2018-095844-B-I00, PGC2018-096444-B-I00, and MAT2017-86659-R), the EUROfusion Consortium through Project ENR-IFE19.CCFE-01, and the Madrid Regional Government (Grants P2018/NMT-4389 and P2018/EMT-4437). A.P. is thankful for the support of FONDECYT under Grants 3190123 and 11180557, as well as from Financiamiento Basal para Centros Cientificos y Tecnologicos de Excelencia FB-0807. K.L. acknowledges the support of the Russian Science Foundation (Project 19-19-00683). The authors acknowledge the computer resources and technical assistance provided by the Centro de Supercomputacion y Visualizacion de Madrid (CeSViMa) and the supercomputing infrastructure of the NLHPC (ECM-02). This Letter is based upon work from COST Action TUMIEE (CA17126)Castro-Palacio, JC.; Ladutenko, K.; Prada, A.; Gonzalez-Rubio, G.; Diaz-Nunez, P.; Guerrero-Martinez, A.; Fernández De Córdoba, P.... (2020). Hollow Gold Nanoparticles Produced by Femtosecond Laser Irradiation. The Journal of Physical Chemistry Letters. 11(13):5108-5114. https://doi.org/10.1021/acs.jpclett.0c01233S51085114111

COVID-19 in Latin America: A Bibliometric Analysis of Scientific Publications in Health

The coronavirus disease (COVID-19) has become a global health crisis. The scientific community has responded with a sizable level of research and publications, many of which are beginning to be identified and analyzed in systematic reviews of the literature and bibliometric studies. No readily identifiable, comparable study focused on Latin American scientific literature has been undertaken thus far. Therefore, this article analyzes such literature, focused on COVID-19, and one that has been published in the scientific journals of the region. A search with the keyword “COVID-19” in the Scientific Electronic Library Online (SciELO) database resulted in the identification of 261 documents. Following PRISMA guidelines, the total number was reduced to 117 for the purpose of the bibliometric analysis (i.e., elimination of preprint duplicates). Such analysis resulted in the following findings: 69 publications were editorial or individual commentaries, and 48 were original articles. The male authors totaled 280, contrasted with 169 female authors. Two Brazilian journals led in the number of publications: Cadernos de Saúde Pública and Clinics. Even though the Latin American scientific productivity regarding COVID-19 is not well represented in the different databases of the region, it is expected that these scientific publications will achieve increased visibility in the coming months. The article emphasizes the importance of systematic and bibliographic reviews ofthe scientific literature in Latin America in orderto evaluate the public health achievements of the region.Fil: Gallegos de San Vicente, Miguel Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto Rosario de Investigaciones en Ciencias de la Educación. Universidad Nacional de Rosario. Instituto Rosario de Investigaciones en Ciencias de la Educación; Argentina. Universidad Catolica de Maule; ChileFil: Cervigni, Mauricio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto Rosario de Investigaciones en Ciencias de la Educación. Universidad Nacional de Rosario. Instituto Rosario de Investigaciones en Ciencias de la Educación; ArgentinaFil: Consoli, Andrés J.. University of California; Estados UnidosFil: Caicho Rodriguez, Tomás. Pontificia Universidad Católica de Perú; PerúFil: Polanco, Fernando Andrés. Universidad Nacional de San Luis. Facultad de Psicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martino, Pablo Luis. Universidad Nacional de Rosario. Facultad de Psicología. Secretaria de Ciencia y Tecnología. Centro de Investigación En Neurociencias de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castro Pecanha, Viviane. University of Chicago; Estados UnidosFil: Buergos Videla, Carmen. Universidad de Atacama.; ChileFil: Polanco Carrasco, Roberto. No especifíca;Fil: Cussinato, Adriana Marie. Universidad de Palermo; Argentina. Universidad Nacional de Rosario; Argentin

Adjuvant dabrafenib and trametinib for patients with resected BRAF-mutated melanoma: DESCRIBE-AD real-world retrospective observational study

BRAF and MEK inhibitor, dabrafenib plus trametinib, adjuvant therapy is effective for high-risk resected melanoma patients with BRAF-V600 mutations. However, real-world evidence is limited. We aimed to determine the feasibility of this therapy in routine clinical practice. DESCRIBE-AD, a retrospective observational study, collected real-world data from 25 hospitals in Spain. Histologically confirmed and resected BRAF-mutated melanoma patients aged & GE;18 years who were previously treated with dabrafenib plus trametinib adjuvant therapy, were included. The primary objectives were treatment discontinuation rate and time to discontinuation. The secondary objectives included safety and efficacy. From October 2020 to March 2021, 65 patients were included. Dabrafenib and trametinib discontinuation rate due to treatment-related adverse events (TRAEs) of any grade was 9%. Other reasons for discontinuation included patients' decisions (6%), physician decisions (6%), unrelated adverse events (3%), disease progression (5%), and others (5%). The median time to treatment discontinuation was 9 months [95% confidence interval (CI), 5-11]. G3-4 TRAEs occurred in 21.5% of patients, the most common being pyrexia (3%), asthenia (3%), and diarrhoea (3%). Unscheduled hospitalisations and clinical tests occurred in 6 and 22% of patients, respectively. After 20-month median follow-up (95% CI, 18-22), 9% of patients had exitus due to disease progression, with a 12-month relapse-free survival and overall survival rates of 95.3% and 100%, respectively. Dabrafenib and trametinib adjuvant therapy proved effective for melanoma patients in a real-world setting, with a manageable toxicity profile. Toxicity frequencies were low leading to low incidence of unscheduled medical visits, tests, and treatment discontinuations

A Functional Pipeline of Genome-Wide Association Data Leads to Midostaurin as a Repurposed Drug for Alzheimer’s Disease

Genome-wide association studies (GWAS) constitute a powerful tool to identify the different biochemical pathways associated with disease. This knowledge can be used to prioritize drugs targeting these routes, paving the road to clinical application. Here, we describe DAGGER (Drug Repositioning by Analysis of GWAS and Gene Expression in R), a straightforward pipeline to find currently approved drugs with repurposing potential. As a proof of concept, we analyzed a meta-GWAS of 1.6 × 107 single-nucleotide polymorphisms performed on Alzheimer’s disease (AD). Our pipeline uses the Genotype-Tissue Expression (GTEx) and Drug Gene Interaction (DGI) databases for a rational prioritization of 22 druggable targets. Next, we performed a two-stage in vivo functional assay. We used a C. elegans humanized model over-expressing the Aβ1-42 peptide. We assayed the five top-scoring candidate drugs, finding midostaurin, a multitarget protein kinase inhibitor, to be a protective drug. Next, 3xTg AD transgenic mice were used for a final evaluation of midostaurin’s effect. Behavioral testing after three weeks of 20 mg/kg intraperitoneal treatment revealed a significant improvement in behavior, including locomotion, anxiety-like behavior, and new-place recognition. Altogether, we consider that our pipeline might be a useful tool for drug repurposing in complex diseases.This work was mainly financed by Programa Operativo FEDER funds from the European Union through grant UMA20-FEDERJA-133. We thank Fundacion SantÁngela for co-funding with grant 83/23.04.2021. P.G.-G. is supported by the CIBERNED employment plan CNV-304-PRF-866. CIBERNED is integrated into Instituto de Salud Carlos III. I.d.R is supported by a national grant from the Instituto de Salud Carlos III FI20/00215. A.R. is supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240, and PI19/01301. A.M.B.-L. and M.J.M. were funded by grant PID2020-120463RB-I00 funded by the Spanish Ministerio de Ciencia e Innovación. A.C.-Z. holds a postdoctoral research contract from Secretaría General de Universidades, Investigación y Tecnología–Junta de Andalucía (POSTDOC21_00365). B.P.S (IFI21/00024) holds an “iPFIS” predoctoral contract from the National System of Health, EU-ERDF-ISCIII. M.d.C.M.-P. holds predoctoral grants from the Spanish Ministry of Science, Innovation and Universities (FPU17/00276). P.R. (CP19/00068) holds a “Miguel Servet” research contract from the National System of Health, ISCIII co-funded by the European Social Fund, “Investing in your future,” Gobierno de España. This research was funded by Delegación del Gobierno para el Plan Nacional sobre Drogas, Ministerio de Salud, Gobierno de España (PND2020/048). Ethovision XT software v17 (Noldus, Wageningen, The Netherlands) funded by Plan Propio, Universidad de Málaga

Non-productive angiogenesis disassembles Aß plaque-associated blood vessels

The human Alzheimer’s disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis is started near Aß plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around Aß plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity. Notably, NPA induction by endothelial loss of presenilin, whose mutations cause familial AD and which activity has been shown to decrease with age, produced a similar vascular phenotype in the absence of Aß pathology. We also show that Aß plaque-associated NPA locally disassembles blood vessels, leaving behind vascular scars, and that microglial phagocytosis contributes to the local loss of endothelial cells. These results define the role of NPA and microglia in local blood vessel disassembly and highlight the vascular component of presenilin loss of function in AD