Corneal nerve loss as a surrogate marker for poor pial collaterals in patients with acute ischemic stroke

In patients with acute ischemic stroke, pial collaterals play a key role in limiting neurological disability by maintaining blood flow to ischemic penumbra. We hypothesized that patient with poor pial collaterals will have greater corneal nerve and endothelial cell abnormalities. In a cross-sectional study, 35 patients with acute ischemic stroke secondary to middle cerebral artery (MCA) occlusion with poor (n = 12) and moderate-good (n = 23) pial collaterals and 35 healthy controls underwent corneal confocal microscopy and quantification of corneal nerve and endothelial cell morphology. In patients with MCA stroke, corneal nerve fibre length (CNFL) (P < 0.001), corneal nerve fibre density (CNFD) (P = 0.025) and corneal nerve branch density (CNBD) (P = 0.002) were lower compared to controls. Age, BMI, cholesterol, triglycerides, HDL, LDL, systolic blood pressure, NIHSS and endothelial cell parameters did not differ but mRS was higher (p = 0.023) and CNFL (p = 0.026) and CNBD (p = 0.044) were lower in patients with poor compared to moderate-good collaterals. CNFL and CNBD distinguished subjects with poor from moderate-good pial collaterals with an AUC of 72% (95% CI 53–92%) and 71% (95% CI 53–90%), respectively. Corneal nerve loss is greater in patients with poor compared to moderate-good pial collaterals and may act as a surrogate marker for pial collateral status in patients with ischemic stroke

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Euclid preparation. XV. Forecasting cosmological constraints for the Euclid and CMB joint analysis

Galaxie

Emergence of structural anisotropy in optical glasses treated to support second harmonic generation

Few discoveries have puzzled the optics community more than the emergence of visible (green) light from optical fibers after strong irradiation by an infrared laser. This frequency-doubling phenomenon known as Second Harmonic Generation (SHG) is not expected to take place in a centrosymmetric material such as the amorphous silica fiber-core, which shows no measurable second-order optical susceptibility χ(2). The process to be efficient also requires well defined phase-matching between the interacting waves to allow for constructive interference, and this seems even more difficult to fulfill within the glassy medium. Several plausible explanations about the origin of the phenomenon have been put forward. One of the most widely accepted does not involve structural modifications to accomplish the breakdown of the glass radial symmetry. Rather, it postulates the emergence of a spatially modulated local dc field, E0, which, via a third-order nonlinearity (χ(3)) (finite in isotropic materials), induces a spatially modulated second order nonlinearity ( χ(2) is proportional to χ(3)E0 ) able to double the pump frequency. The achievement of a permanent χ(2) in optical glasses has focused a large research effort, which lead to the discovery of alternative poling techniques. In actual fact, the phenomenon can be produced by application of a high voltage (~5 kV, just below dielectric breakdown) to glass plates at moderate temperatures (~540 - 580 K, compared with ~ 1475 K where the glass melts). This method, known as "thermal" poling provides permanent second-order nonlinear responses comparable to those shown by inorganic crystals. Whether the mechanism(s) leading to the emergence of a second order non-linearity in "thermally-poled" glasses differ from those of photoinduced SHG or not needs to be clarified. At any rate, the relevant point stems from the possibility this method has opened up for developing inexpensive integrated optical frequency converters and electro-optic modulators

Design, synthesis, and biological evaluation of hybrid molecules containing alpha-methylene-gamma-butyrolactones and polypyrrole minor groove binders

Hybrids of polypyrrole minor groove binders structurally related to the natural antitumor agent distamycin A and -methylene--butyrolactones with Me, Ph, and 4-substituted Ph groups at the lactone C() position were prepd. and evaluated for in vitro cytotoxic activity against a variety of cancer cell lines. The apoptotic and cytotoxic activities against several tumor cell lines were reported and discussed in terms of their structural differences in relation to both the no. of N-methylpyrrole rings and the type of the alkylating unit tethered to the oligopeptidic frame. For polypyrroles I [R = C(:NH)NH2, n = 2, 3; R = NHC(:NH)NH2, n = 3] the cytotoxicity of the hybrids was much greater than that of the -methylene--butyrolactone units II (R1 = Me, Ph, 4-ClC6H4, 4-PhC6H4; m = 1, 3, 5, 7) alone. Using the human leukemia cell line HL-60, the effects of a selected series of compds. on programmed cell death (apoptosis) were detd. I [R = C(:NH)NH2, n = 2, 3; R = NHC(:NH)NH2, n = 3] induce apoptosis as demonstrated from identification of nuclear changes assocd. with apoptosis using fluorescence microscopy and by DNA laddering on agarose gel electrophoresis. I [R = C(:NH)NH2, n = 2] was the most potent, esp. after a short incubation period. It induced extensive hydrolysis of poly ADP-ribose polymerase (PARP), considered to be a hallmark of apoptosis, which plays a crit. role in chromatin architecture and DNA metab

Folate-related polymorphisms in gastrointestinal stromal tumours: susceptibility and correlation with tumour characteristics and clinical outcome

The folate metabolism pathway has a crucial role in tumorigenesis as it supports numerous critical intracellular reactions, including DNA synthesis, repair, and methylation. Despite its importance, little is known about the influence of the folate pathway on gastrointestinal stromal tumour (GIST), a rare tumour with an incidence ranging between 6 and 19.6 cases per million worldwide. The importance of folate metabolism led us to investigate the influence of polymorphisms in the genes coding folate-metabolising enzymes on GIST susceptibility, tumour characteristics and clinical outcome. We investigated a panel of 13 polymorphisms in 8 genes in 60 cases and 153 controls. The TS 6-bp deletion allele (formerly rs34489327, delTInsTTAAAG) was associated with reduced risk of GIST (OR=0.20, 95% CI 0.05-0.67, P=0.0032). Selected polymorphisms in patients stratified by age, gender, and other main molecular and clinical characteristics showed that few genotypes may show a likely correlation. We also observed a significant association between the RFC AA/AG genotype and time to progression (HR=0.107, 95% CI 0.014-0.82; P=0.032). Furthermore, we observed a tendency towards an association between the SHMT1 variant allele (TT, rs1979277) and early death (HR=4.53, 95% CI 0.77-26.58, P=0.087). Aware of the strengths and limitations of the study, these results suggest that polymorphisms may modify the risk of GIST and clinical outcome, pointing to the necessity for further investigations with information on folate plasma levels and a larger study population

Evidence of microscopic-scale modifications in optical glasses supporting second harmonic generation

We explore the extent of changes in dynamic correlations of vitreous SiO2 induced by treatments required to enable frequency doubling of infrared light (poling) by means of inelastic neutron scattering. These appear as an excess of modes in certain regions of the frequency spectrum as well as a narrowing of the 100 meV peak. Such alterations are better ascribed to a change in ordering of the material than to the emergence of "defect" modes, absent in the native sample