The consequences of the SARS-CoV-2 pandemic have exceeded any forecast made. Today we know that the level of severity of the infection in its initial stages will correspond to the evolution and the ...presence of sequelae in the future. There are no specific treatments that have shown sufficient evidence to allow their recommendation, especially in the mild-moderate stages of the disease. The anti-Covid vaccination is showing clear benefits, both in the prevention of the disease and in its evolution, with the consequent improvement in the numbers of those affected by the pandemic. The use of different drugs used in other indications has been proposed as possible beneficial treatments for COVID-19 that, if used, will be prescribed individually taking into account the characteristics and situation of the patient, the evolutionary phase of the disease as well as well as the limitations of the lack of evidence in its administration.
COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements ...and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals' 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.
OBJECTIVETo investigate the visual and anatomical outcomes of aflibercept as therapy in patients with treatment-naïve neovascular age-related macular degeneration during one year in routine clinical ...practice. METHODSThe study was a retrospective, case series, including 35 patients, 38 eyes, with neovascular age-related macular degeneration that received aflibercept injections (Eylea®). Patients received a loading dose of 3monthly injections (2mg / 0.05ml) followed by intravitreal injections every 2 months. RESULTSAt 3 and 12 months, the mean best-corrected visual acuity improved significantly as compared with baseline (ETDRS 50.5±14.5 and 53.1±14.5 vs. 39.6±14.7, respectively, P<.05). At 3 and 12 months, the proportion of patients who improved visual acuity by ≥15 letters was 37.1% and 45.7%, respectively. The mean decrease in central macular thickness was also significant after loading dose (239.6±52.0μm) and at 12 month (227±53.2μm) compared with pre-treatment values (370.3±117, 6) (P<.001). Resolution of pigment epithelial detachment (PED) was also observed in 14 out of 20 (70%) eyes with PED at baseline. CONCLUSIONAflibercept administered by fixed dosing over one year improved visual acuity and macular morphology in treatment-naïve eyes in routine daily practice.
This article presents a dimension-reduction method in quadratic discriminant analysis (QDA). The procedure is inspired by the geometric relation that exists between the subspaces used in sliced ...inverse regression (SIR) and sliced average variance estimation (SAVE). A new set of directions is constructed to improve the properties of the directions associated with the eigenvectors of the matrices usually considered for dimension reduction in QDA. Illustrative examples of application with real and simulated data are discussed.
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The survival of women with cystic fibrosis (CF) is lower than that of men by approximately 5 years. While various factors have been put forward to account for this discrepancy, no ...specific reasons have been established. Our hypothesis was that anatomical-structural involvement is more pronounced in women with CF than in men and that this is reflected in thoracic HRCT findings.
We performed a prospective multicentre study, in which adult patients were consecutively included over 18 months. Chest HRCT was performed, and findings were scored by 2 thoracic radiologists using the modified Bhalla system. We also studied respiratory function, applied the CFQR 14+ questionnaire, and collected clinical variables.
Of the 360 patients followed up in the participating units, 160 were eventually included. Mean age was 28 years, and 47.5% were women. The mean±SD global score on the modified Bhalla score was 13.7±3.8 in women and 15.2±3.8 in men (p=0.024). The highest scores were observed for sacculations, bronchial generations, and air trapping in women. Women had lower BMI, %FEV1, %FVC, and %DLCO. Similarly, the results for the respiratory domain in CFQR 14+ were worse in women, who also had more annual exacerbations.
This is the first study to provide evidence of the implication of sex differences in HRCT findings in patients with CF. Women with CF present a more severe form of the disease that results in more frequent exacerbations, poorer functional and nutritional outcomes, deterioration of quality of life, and greater structural damage.
La supervivencia de las mujeres con fibrosis quística (FQ) es menor que la de los varones, en aproximadamente 5 años. Si bien se han presentado varios factores para explicar esta discrepancia, no se han establecido razones específicas. Nuestra hipótesis fue que el compromiso anatómico-estructural es más pronunciado en las mujeres con FQ que en los varones, y que esto se refleja en los hallazgos de la TCAR torácica.
Realizamos un estudio prospectivo multicéntrico, en el que los pacientes adultos se fueron incluyendo consecutivamente durante 18 meses. Se realizó un TCAR de tórax, y 2 radiólogos torácicos evaluaron los hallazgos utilizando la escala de Bhalla modificada. También estudiamos la función respiratoria, aplicamos el cuestionario CFQR 14+ y recogimos ciertas variables clínicas.
De los 360 pacientes en seguimiento en las unidades participantes, finalmente se incluyeron 160. La edad media fue de 28 años, y el 47,5% eran mujeres. La puntuación global media±DE en la escala de Bhalla modificada fue de 13,7±3,8 en mujeres y de 15,2±3,8 en varones (p=0,024). Las puntuaciones más altas se observaron para las saculaciones o abscesos, las generaciones bronquiales y el atrapamiento de aire en mujeres. Las mujeres tenían un IMC, % FEV1, % FVC y % DLCO más bajos. Del mismo modo, los resultados para el dominio respiratorio en el CFQR 14+ fueron peores en las mujeres, que también tenían más exacerbaciones anuales.
Este es el primer estudio que proporciona evidencia de la implicación de las diferencias de sexo en los hallazgos de la TCAR en pacientes con FQ. Las mujeres con FQ presentan una forma más grave de la enfermedad que resulta en exacerbaciones más frecuentes, peores resultados funcionales y nutricionales, deterioro de la calidad de vida y mayor daño estructural.
Abstract
Background
Chromosome abnormalities are a frequent finding in prenatal invasive testing for fetal malformations and/or growth retardation.
Case presentation
We present a case of low level ...(8%) mosaic trisomy 15 detected on amniocentesis after fetal heart anomalies and IUGR (intrauterine growth retardation) were found on routine scan. Postnatal karyotype confirmed a very low level (2%) mosaicism in the skin but not in blood lymphocytes or in the urine. Methylation specific testing of chromosome 15 showed maternal uniparental disomy and consequently the newborn was diagnosed with Prader-Willi syndrome (PWS).
Conclusions
This case illustrates the need of further genetic testing in all trisomy 15 mosaicisms detected in prenatal invasive testing in order to screen for PWS, a more frequent entity than trisomy 15, altogether providing appropriate genetic counseling and adequate clinical management. The recommendation is applicable to prenatally detected mosaic trisomies of other chromosomes carrying imprinted genes, such as 7, 11 and 14.
AbstractThe influence of Versailles on L’Enfant’s 1791 plan for the city of Washington, DC, is well known. Less well known are the surprising similarities between Washington and the forma urbis of ...the Royal Site of Aranjuez in Spain. For example, the cities share the same diagram of two large, rectangular spaces arranged in an L shape, at the extremes of which are located, analogously, the most emblematic buildings: The Capitol and the White House in one instance, and the Royal Palace and the Church of San Antonio in the other. There are also connections between some of the diagonal avenues; between the Plaza de las Doce Calles in Aranjuez and the 12 avenues radiating from the Capitol; and between the trident of Parterre Garden in Aranjuez and the trident formed in L’Enfant’s plan by Pennsylvania Avenue NW, Maryland Avenue SW, and Avenue H. Based on these facts, this paper investigates parallels that have hitherto been ignored. It is not possible to conclude, based on the currently available information, that L’Enfant was familiar with the plan for Aranjuez, which was sent in 1775 to the main European courts, where it is conserved in their libraries. A copy of the plan is also the Library of Congress in Washington, DC. There is evidence that L’Enfant’s father, and possibly he himself, saw it in Paris at the Académie Royale de Peinture et de Sculpture, at which L’Enfant was studying before his departure for the United States. He may also have seen it during a visit to Paris in 1783, when the creation of a new capital had been proposed and he was a candidate to plan it because of his relationship with George Washington. Similarly, Thomas Jefferson may have seen the plan during his time as ambassador in Paris, given that, in his own sketch for the new capital, he situated the White House and the Capitol in the same compositional relationship as L’Enfant did later. These similarities may also simply be coincidence; in any case, they invite questions.
•The use of reporter proteins has revolutionised the research on infectious diseases.•The expression of reporter proteins must cover the whole parasite's life-cycle.•High-Throughput Screenings have ...greater acceptance for drug discovery studies.•In vivo imaging of transgenic parasites is suitable for pre-clinical trials.•Reporter proteins have opened up new advances in genetic exchange of trypanosomatids.
The use of genetically engineered pathogens that express fluorescent or luminescent proteins represents a huge stride forward in the understanding of trypanosomatid-borne tropical diseases. Nowadays, such modified microorganisms are being used to screen thousands of compounds under a target-free (phenotypic) approach. In addition, experimental infections with transgenic parasites drastically reduce the number of animals required for preclinical studies, because no animal needs to be put down to assess its parasite load. Finally, the use of fluorescent parasites is contributing to unraveling genetic exchange events between trypanosomatid strains. This phenomenon is important for understanding the mechanism by which traits such as virulence, tissue tropism, and drug resistance are transferred, as well as the emergence of novel strains.
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Gemin5 is a multifunctional RNA binding protein (RBP) organized in domains with a distinctive structural organization. The protein is a hub for several protein networks performing ...diverse RNA-dependent functions including regulation of translation, and recognition of small nuclear RNAs (snRNAs). Here we sought to identify the presence of phosphoresidues on the C-terminal half of Gemin5, a region of the protein that harbors a tetratricopeptide repeat (TPR)-like dimerization domain and a non-canonical RNA binding site (RBS1). We identified two phosphoresidues in the purified protein: P-T897 in the dimerization domain and P-T1355 in RBS1. Replacing T897 and T1355 with alanine led to decreased translation, and mass spectrometry analysis revealed that mutation T897A strongly abrogates the association with cellular proteins related to the regulation of translation. In contrast, the phosphomimetic substitutions to glutamate partially rescued the translation regulatory activity. The structural analysis of the TPR dimerization domain indicates that local rearrangements caused by phosphorylation of T897 affect the conformation of the flexible loop 2–3, and propagate across the dimerization interface, impacting the position of the C-terminal helices and the loop 12–13 shown to be mutated in patients with neurological disorders. Computational analysis of the potential relationship between post-translation modifications and currently known pathogenic variants indicates a lack of overlapping of the affected residues within the functional domains of the protein and provides molecular insights for the implication of the phosphorylated residues in translation regulation.
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