Association Between Preschoolers' Specific Fine (But Not Gross) Motor Skills and Later Academic Competencies: Educational Implications

Motor development is an inseparable component of cognitive development. So, to develop the mind, it is necessary to work the body. Therefore, Early Childhood Education curricula and the scientific literature emphasize the need to promote the development of motor skills during the 1st years of life. These skills are necessary for learning and subsequent academic performance. However, studies frequently offer only a partial view of these relationships. Few works have analyzed the specific relationships between different components of preschool gross and fine motor skills and subsequent performance on different academic competencies. Further, they present discrepant results. The aim of this study was to determinate which specific components of gross and fine motor skills assessed in Spanish students during the final year of Early Childhood Education (5 to 6-year-olds) were associated with different academic competencies assessed in the following academic year, when the students were in their 1st year of Primary Education. The final sample consisted of 38 Spanish students, aged 5. A mixed methods approach was used. It consisted of systematic observation to assess specific components of gross and fine motor skills when children were in the Early Childhood Education period, and selective methodology to evaluate their academic competencies (specifically in literacy and mathematics and overall), 1 year later, once in Primary Education. Multiple linear regression models were constructed using the computing language R to examine the association between motor skills and academic competencies. The results indicated that only the components of fine motor skills showed associations with academic competencies. The pattern of association varied when literacy and mathematics competencies were specifically and individually assessed and when overall academic competency was considered. The two assessed fine motor skills (Coordination and Integration) were associated with literacy competency (β = 0.344, p = 0.025; β = 0.349, p = 0.024, respectively) and overall academic competency (β = 0.267, p = 0.065; β = 0.493, p = 0.001, respectively). However, only Integration was associated with mathematics competency (β = 0.476, p = 0.002). The 'Discussion' section focuses on the educational implications of these results and future research. It highlights the importance of early assessment of fine motor skills to identify students likely to present inadequate subsequent academic performance and the need to apply instruction and interventions tailored to the specific needs of each child

T-pattern detection in the scientific literature of this century: A systematic review

Scientific literature contains mainly systematic reviews focused on substantial aspects, but there are also approaches that have combined both substantial and methodological aspects, which is our preferred option since it undeniably adds value. The aims of this study were: (1) to carry out a systematic review of the literatura on T-Pattern analysis (TPA), and (2) to explore the possible contribution of mixed methods research to the integration of qualitative and quantitative elements on a synthesis level.Methods: Based on PRISMA guidelines, searches were carried out in the Scopus, PsycINFO, and Web of Science databases. The general search syntax was: “THEME” AND (“T-Patterns” OR “T Patterns”) carried out in title, keywords and abstract. In addition, we included empirical articles on THEME and T-Patterns collected in other sources based on citations in several empirical works and consultations with different authors. This selection process resulted in 125 primary documents making up this systematic review. Results: The results showed that the detection of structures in behavior patterns forms a nexus between studies carried out in very diverse fields and contexts. Most studies are observational, whilst the applicability and power of T-Pattern detection are extraordinary. It allows the researcher to go deeper in a robust analysis that responds to the integration of qualitative and quantitative elements which constitutes the leit motive of mixed methods; and also to discover the deep, hidden structure that underlies the respective databases, regardless of the methodology used in each study. The possibilities in assigning parameters notably increase the options for obtaining results and their interpretation. Discussion: It is relevant the extraordinary strength and applicability of T-pattern detection. There is a high presence of T-pattern detection and analysis in studies using observational methodology. It is necessary commit to consolidating the methodological analysis of selected works, as taking individual and collective responsibility for improving methodological quality of TPA studies, taking advantage of the resources provided by the THEME program

Transcriptomic and Metabolomic Response to High Light in the Charophyte Alga Klebsormidium nitens

The characterization of the molecular mechanisms, such as high light irradiance resistance, that allowed plant terrestralization is a cornerstone in evolutionary studies since the conquest of land by plants played a pivotal role in life evolution on Earth. Viridiplantae or the green lineage is divided into two clades, Chlorophyta and Streptophyta, that in turn splits into Embryophyta or land plants and Charophyta. Charophyta are used in evolutionary studies on plant terrestralization since they are generally accepted as the extant algal species most closely related to current land plants. In this study, we have chosen the facultative terrestrial early charophyte alga Klebsormidium nitens to perform an integrative transcriptomic and metabolomic analysis under high light in order to unveil key mechanisms involved in the early steps of plants terrestralization. We found a fast chloroplast retrograde signaling possibly mediated by reactive oxygen species and the inositol polyphosphate 1-phosphatase (SAL1) and 3′-phosphoadenosine-5′-phosphate (PAP) pathways inducing gene expression and accumulation of specific metabolites. Systems used by both Chlorophyta and Embryophyta were activated such as the xanthophyll cycle with an accumulation of zeaxanthin and protein folding and repair mechanisms constituted by NADPH-dependent thioredoxin reductases, thioredoxin-disulfide reductases, and peroxiredoxins. Similarly, cyclic electron flow, specifically the pathway dependent on proton gradient regulation 5, was strongly activated under high light. We detected a simultaneous co-activation of the non-photochemical quenching mechanisms based on LHC-like stress related (LHCSR) protein and the photosystem II subunit S that are specific to Chlorophyta and Embryophyta, respectively. Exclusive Embryophyta systems for the synthesis, sensing, and response to the phytohormone auxin were also activated under high light in K. nitens leading to an increase in auxin content with the concomitant accumulation of amino acids such as tryptophan, histidine, and phenylalanine.España Ministerio de Ciencia e Innovación MINOTAUR (BIO2017-84066-R

The Origin, Epidemiology, and Phylodynamics of Human Immunodeficiency Virus Type 1 CRF47_BF

CRF47_BF is a circulating recombinant form (CRF) of the human immunodeficiency virus type 1 (HIV-1), the etiological agent of AIDS. CRF47_BF represents one of 19 CRFx_BFs and has a geographic focus in Spain, where it was first identified in 2010. Since its discovery, CRF47_BF has expanded considerably in Spain, predominantly through heterosexual contact (∼56% of the infections). Little is known, however, about the origin and diversity of this CRF or its epidemiological correlates, as very few samples have been available so far. This study conducts a phylogenetic analysis with representatives of all CRFx_BF sequence types along with HIV-1 M Group subtypes to validate that the CRF47_BF sequences share a unique evolutionary history. The CRFx_BF sequences cluster into a single, not well supported, clade that includes their dominant parent subtypes (B and F). This clade also includes subtype D and excludes sub-subtype F2. However, the CRF47_BF sequences all share a most recent common ancestor. Further analysis of this clade couples CRF47_BF protease-reverse transcriptase sequences and epidemiological data from an additional 87 samples collected throughout Spain, as well as additional CRF47_BF database sequences from Brazil and Spain to investigate the origin and phylodynamics of CRF47_BF. The Spanish region with the highest proportion of CRF47_BF samples in the data set was the Basque Country (43.7%) with Navarre next highest at 19.5%. We include in our analysis epidemiological data on host sex, mode of transmission, time of collection, and geographic region. The phylodynamic analysis indicates that CRF47_BF originated in Brazil around 1999-2000 and spread to Spain from Brazil in 2002-2003. The virus spread rapidly throughout Spain with an increase in population size from 2011 to 2015 and leveling off more recently. Three strongly supported clusters associated with Spanish regions (Basque Country, Navarre, and Aragon), together comprising 60.8% of the Spanish samples, were identified, one of which was also associated with transmission among men who have sex with men. The expansion in Spain of CRF47_BF, together with that of other CRFs and subtype variants of South American origin, previously reported, reflects the increasing relationship between the South American and European HIV-1 epidemics.The study was supported by Acción Estratégica en Salud Intramural (AESI) program of Instituto de Salud Carlos III, projects “Estudio sobre Vigilancia Epidemiológica Molecular de la Infección por VIH-1 en España,” PI16CIII/00033, and “Epidemiología Molecular del VIH-1 en España y su Utilidad para Investigaciones Biológicas y en Vacunas,” PI19CIII/00042; Red de Investigación en SIDA (RIS), Instituto de Salud Carlos III, Plan Nacional I+D+I, project RD16ISCIII/0002/0004; and scientific agreements with the Governments of Galicia (MVI 1004/16) and Basque Country (MVI 1001/16).N

Exploring genetic factors involved in huntington disease age of onset. E2F2 as a new potential modifier gene

Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO), and the first motor symptoms age (motor AO or mAO). Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample of 35 HD patients from Basque Country Hospitals. We found suggestive association signals between HD eAO and/or mAO and genetic variation within the E2F2, ATF7IP, GRIN2A, GRIN2B, LINC01559, HIP1 and GRIK2 genes. Among them, the most significant was the association between eAO and rs2742976, mapping to the promoter region of E2F2 transcription factor. Furthermore, rs2742976 T allele patient carriers exhibited significantly lower lymphocyte E2F2 gene expression, suggesting a possible implication of E2F2-dependent transcriptional activity in HD pathogenesis. Thus, E2F2 emerges as a new potential HD AO modifier factor

Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial

The paper assesses the dose-limiting toxicities and the maximum tolerated dose (MTD) of trastuzumab emtansine (T-DM1) combined with non-pegylated liposomal doxorubicin (NPLD) in HER2-positive (HER2+) metastatic breast cancer (MBC). This single-arm, open-label, phase Ib trial (NCT02562378) enrolled anthracycline-naïve HER2+ MBC patients who had progressed on trastuzumab and taxanes. Patients received a maximum of 6 cycles of NPLD intravenously (IV) at various dose levels (45, 50, and 60 mg/m2) in the "3 plus 3" dose-escalation part. During expansion, they received 60 mg/m2 of NPLD every 3 weeks (Q3W) plus standard doses of T-DM1. The MTD was T-DM1 3.6 mg/kg plus NPLD 60 mg/m2 administered IV Q3W. No clinically relevant worsening of cardiac function was observed. Among all evaluable patients, the overall response rate was 40.0% (95%CI, 16.3-67.7) with a median duration of response of 6.9 months (95%CI, 4.8-9.1). Clinical benefit rate was 66.7% (95%CI, 38.4-88.2) and median progression-free survival was 7.2 months (95%CI, 4.5-9.6). No significant influence of NPLD on T-DM1 pharmacokinetics was observed. The addition of NPLD to T-DM1 is feasible but does not seem to improve the antitumor efficacy of T-DM1 in HER2+ MBC patients

Phylogeny and phylogeography of a recent HIV-1 subtype F outbreak among men who have sex with men in Spain deriving from a cluster with a wide geographic circulation in Western Europe

This work received support from the Dirección General de Farmacia, Ministerio de Sanidad, Servicios Sociales e Igualdad, Government of Spain, grant EC11-272; European Network of Excellence EUROPRISE (Rational Design of HIV Vaccines and Microbicides), grant LSHP-CT-2006-037611; European Research Infrastructures for Poverty Related Diseases (EURIPRED). Seventh Framework Programme: FP7-Capacities-infrastructures-2012-1, grant agreement 312661; Instituto de Salud Carlos III, Subdirección General de Evaluación, and Fondo Europeo de Desarrollo Regional (FEDER), Plan Nacional I + D + I, through project RD12/0017/0026; Consellería de Sanidade, Government of Galicia, Spain (MVI 1291/08); and the Osakidetza-Servicio Vasco de Salud, Basque Country, Spain (MVI-1255-08). Marcos Pérez-Losada was supported by a DC D-CFAR Research Award from the District of Columbia Developmental Center for AIDS Research (P30AI087714) and by an University Facilitating Fund award from George Washington University. Aurora Fernández-García is supported by CIBER in Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid, Spain.We recently reported the rapid expansion of an HIV-1 subtype F cluster among men who have sex with men (MSM) in the region of Galicia, Northwest Spain. Here we update this outbreak, analyze near full-length genomes, determine phylogenetic relationships, and estimate its origin. For this study, we used sequences of HIV-1 protease-reverse transcriptase and env V3 region, and for 17 samples, near full-length genome sequences were obtained. Phylogenetic analyses were performed via maximum likelihood. Locations and times of most recent common ancestors were estimated using Bayesian inference. Among samples analyzed by us, 100 HIV-1 F1 subsubtype infections of monophyletic origin were diagnosed in Spain, including 88 in Galicia and 12 in four other regions. Most viruses (n = 90) grouped in a subcluster (Galician subcluster), while 7 from Valladolid (Central Spain) grouped in another subcluster. At least 94 individuals were sexually-infected males and at least 71 were MSM. Seventeen near full-length genomes were uniformly of F1 subsubtype. Through similarity searches and phylogenetic analyses, we identified 18 viruses from four other Western European countries [Switzerland (n = 8), Belgium (n = 5), France (n = 3), and United Kingdom (n = 2)] and one from Brazil, from samples collected in 2005?2011, which branched within the subtype F cluster, outside of both Spanish subclusters, most of them corresponding to recently infected individuals. The most probable geographic origin and age of the Galician subcluster was Ferrol, Northwest Galicia, around 2007, while the Western European cluster probably emerged in Switzerland around 2002. In conclusion, a recently expanded HIV-1 subtype F cluster, the largest non-subtype B cluster reported in Western Europe, continues to spread among MSM in Spain; this cluster is part of a larger cluster with a wide geographic circulation in diverse Western European countries.Publisher PDFPeer reviewe

Transcriptional analysis of the HeT-A retrotransposon in mutant and wild type stocks reveals high sequence variability at Drosophila telomeres and other unusual features

<p>Abstract</p> <p>Background</p> <p>Telomere replication in Drosophila depends on the transposition of a domesticated retroelement, the <it>HeT-A </it>retrotransposon. The sequence of the <it>HeT-A </it>retrotransposon changes rapidly resulting in differentiated subfamilies. This pattern of sequence change contrasts with the essential function with which the <it>HeT-A </it>is entrusted and brings about questions concerning the extent of sequence variability, the telomere contribution of different subfamilies, and whether wild type and mutant Drosophila stocks show different <it>HeT-A </it>scenarios.</p> <p>Results</p> <p>A detailed study on the variability of <it>HeT-A </it>reveals that both the level of variability and the number of subfamilies are higher than previously reported. Comparisons between GIII, a strain with longer telomeres, and its parental strain Oregon-R indicate that both strains have the same set of <it>HeT-A </it>subfamilies. Finally, the presence of a highly conserved splicing pattern only in its antisense transcripts indicates a putative regulatory, functional or structural role for the <it>HeT-A </it>RNA. Interestingly, our results also suggest that most <it>HeT-A </it>copies are actively expressed regardless of which telomere and where in the telomere they are located.</p> <p>Conclusions</p> <p>Our study demonstrates how the <it>HeT-A </it>sequence changes much faster than previously reported resulting in at least nine different subfamilies most of which could actively contribute to telomere extension in Drosophila. Interestingly, the only significant difference observed between Oregon-R and GIII resides in the nature and proportion of the antisense transcripts, suggesting a possible mechanism that would in part explain the longer telomeres of the GIII stock.</p

High frequency of low-count monoclonal B-cell lymphocytosis in hospitalized COVID-19 patients

Low-count monoclonal B-cell lymphocytosis (MBLlo, <500 clonal B-cells/μL) is a highly prevalent condition in the general population (4% to 16% of otherwise healthy adults), which increases significantly with age.1-7 In most cases, clonal B-cells share phenotypic and cytogenetic features with chronic lymphocytic leukemia (CLL), but only a small fraction (≈1.8%) progresses to high-count MBL (MBLhi; ≥500 and <5000 clonal B-cells/μL)3 in the medium-term.8 However, previous reports showed that MBLlo subjects had an increased risk of severe infections in association with a (predominantly) secondary antibody deficiency,8-10 suggesting that MBLlo might be a risk marker for developing more severe infections.This work was supported by the Instituto de Salud Carlos III (Ministerio de Ciencia e Innovación, Madrid, Spain, and FONDOS FEDER (a way to build Europe) grants CB16/12/00400 (CIBERONC), COV20/00386, and PI17/00399; the Consejería de Educación and the Gerencia Regional de Salud, Consejería de Sanidad from Junta de Castilla y León (Valladolid, Spain) grants SA109P20 and GRS-COVID-33/A/20; the European Regional Development Fund (INTERREG POCTEP Spain-Portugal) grant 0639-IDIAL-NET-3-3; and the CRUK (United Kingdom), Fundación AECC (Spain), and Associazione Italiana per la Ricerca Sul Cancro (Italy) “Early Cancer Research Initiative Network on MBL (ECRINM3)” ACCELERATOR award. G.O.-A. is supported by a grant from the Consejería de Educación, Junta de Castilla y León (Valladolid, Spain); B.F.-H. was supported by grant 0639-IDIAL-NET-3-3.Peer reviewe