Collagen organization, polarization sensitivity and image quality in human corneas using second harmonic generation microscopy

In this paper, a Second-Harmonic-Generation (SHG) microscope was used to study the relationship between collagen structural arrangement, image quality and polarization sensitivity in human corneas with different organizations. The degree of order (or alternatively, the Structural Dispersion, SD) was quantified using the structure tensor method. SHG image quality was evaluated with different objective metrics. Dependence with polarization was quantified by means of a parameter defined as polarimetric modulation, which employs polarimetric SHG images acquired with four independent polarization states. There is a significant exponential relationship between the quality of the SHG images and the SD of the samples. Moreover, polarization sensitivity strongly depends on collagen arrangement. For quasi- or partially organized specimens, there is a polarization state that noticeably improves the image quality, providing additional information often not seen in other SHG images. This does not occur in non-organized samples. This fact is closely related to polarimetric modulation, which linearly decreases with the SD. Understanding in more detail the relationships that take place between collagen distribution, image quality and polarization sensitivity brings the potential to enable the development of optimized SHG image acquisition protocols and novel objective strategies for the analysis and detection of pathologies related to corneal collagen disorders, as well as surgery follow-ups

Estudio citogenético de 38 pacientes con síndrome de turner

Among 36 patients with Turner syndrome diagnosis, 20 had the classical karyotype 45, XO and one had 45, X O/46, X X . The remainder 17 patients had different structural aberrations: ten had one or two lines with long arm isochrornosomes, eight of which were 45,XO mosaicism; one patient had 46,X.del (Xp) or 46, X, tel (Xq) because of total lack of the short arm; three had different percentages of monosomic lines and X rings: 45, X0/46, X, r (X); two had structural aberrations of the Y chromosome: 45, X0/46, and  45,XO/46, X, idic (Yq), and one had 45,X0/46,X,f(X). These patients were referred for clinical and cytogenetic evaluation to the Genetic Group of Colombian National Institute of Health during  the 1.977-1983 period. Observations about the possible origin of chromosomal abnormalities, parental ages, patient's ages, motive of consultation and clinical findings are discussed.De 38 pacientes con síndrome de Turner, 20 presentaron el cariotipo clásico 45,X0 y una el mosaico 45,X0/46,XX. Las otras 17 pacientes mostraron diferentes anomalías estructurales: diez tenían una o dos líneas con isocromosomas de brazos largos, ocho de ellas con mosaicismo 45,X0; una paciente presentó 46,X, deI (Xp) o 46,X,tel (Xq) por tratarse de una falta total de brazos cortos; tres mostraron diferentes porcentajes de líneas monosómicas y anillos X: 45,X0/46,X.dXI; dos pacientes tenían anomalías estructurales d el cromosoma Y: 45,X/46, XY nf y 45.X0/46.X.idic (Yq) y una paciente mostró 45,X0/46,X.f (X). Estas pacientes fueron remitidas para evaluación clínica y citogenetica al Grupo de Gen6tica del Instituto Nacional de Salud de Colombia, de 1977 a 1983. Se discuten algunas observaciones sobre el posible origen de las anomalías cromosómicas, la edad de los padres, las edades y motivos de consulta de las pacientes y los hallazgos clínico

Bone marrow activation in response to metabolic syndrome and early atherosclerosis.

Experimental studies suggest that increased bone marrow (BM) activity is involved in the association between cardiovascular risk factors and inflammation in atherosclerosis. However, human data to support this association are sparse. The purpose was to study the association between cardiovascular risk factors, BM activation, and subclinical atherosclerosis. Whole body vascular 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) was performed in 745 apparently healthy individuals [median age 50.5 (46.8-53.6) years, 83.8% men] from the Progression of Early Subclinical Atherosclerosis (PESA) study. Bone marrow activation (defined as BM 18F-FDG uptake above the median maximal standardized uptake value) was assessed in the lumbar vertebrae (L3-L4). Systemic inflammation was indexed from circulating biomarkers. Early atherosclerosis was evaluated by arterial metabolic activity by 18F-FDG uptake in five vascular territories. Late atherosclerosis was evaluated by fully formed plaques on MRI. Subjects with BM activation were more frequently men (87.6 vs. 80.0%, P = 0.005) and more frequently had metabolic syndrome (MetS) (22.2 vs. 6.7%, P < 0.001). Bone marrow activation was significantly associated with all MetS components. Bone marrow activation was also associated with increased haematopoiesis-characterized by significantly elevated leucocyte (mainly neutrophil and monocytes) and erythrocyte counts-and with markers of systemic inflammation including high-sensitivity C-reactive protein, ferritin, fibrinogen, P-selectin, and vascular cell adhesion molecule-1. The associations between BM activation and MetS (and its components) and increased erythropoiesis were maintained in the subgroup of participants with no systemic inflammation. Bone marrow activation was significantly associated with high arterial metabolic activity (18F-FDG uptake). The co-occurrence of BM activation and arterial 18F-FDG uptake was associated with more advanced atherosclerosis (i.e. plaque presence and burden). In apparently healthy individuals, BM 18F-FDG uptake is associated with MetS and its components, even in the absence of systemic inflammation, and with elevated counts of circulating leucocytes. Bone marrow activation is associated with early atherosclerosis, characterized by high arterial metabolic activity. Bone marrow activation appears to be an early phenomenon in atherosclerosis development.[Progression of Early Subclinical Atherosclerosis (PESA); NCT01410318].The PESA study is funded by the CNIC and Santander Bank. The present study was partially funded by an intramural grant CNIC-Severo Ochoa to D.S. and B.I. B.I. is supported by the European Commission (H2020-HEALTH 945118 and ERC-CoG 819775). The CNIC is supported by the ISCIII, the Ministry of Science and Innovation, and the Pro CNIC Foundation. CNIC is a Severo Ochoa Center of Excellence (CEX2020-001041-S).S

Fruit and Vegetable Consumption is Inversely Associated with Plasma Saturated Fatty Acids at Baseline in Predimed Plus Trial

I.D.-L. is supported by the [FI_B 00256] from the FI-AGAUR Research Fellowship Program, Generalitat de Catalunya and M.M.-M is supported by the FPU17/00513 grant. a.-H. is supported by the [CD17/00122] grant and S.K.N. is supported by a Canadian Institutes of Health Research (CIHR) Fellowship. We also thank all the volunteers for their participation in and the personnel for their contribution to the PREDIMED-Plus trial. This research was funded by CiCYT [AGL2016-75329-R] and CIBEROBN from the Instituto de Salud Carlos III, ISCIII from the Ministerio de Ciencia, Innovacion y Universidades, (AEI/FEDER, UE), Generalitat de Catalunya (GC) [2017SGR196]. The PREDIMED-Plus trial was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS), which is co-funded by the European Regional Development Fund (four coordinated Fondo de Investigaciones Sanitarias projects lead by J.S.-S. and J.V., 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, PI17/00926 and PI19/00781), the Especial Action Project entitled Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant to J.S.-S., European Research Council (Advanced Research Grant 2014-2019, 340918) to M.a.M.-G., the Recercaixa grant to J.S.-S. (2013ACUP00194), grants from the Consejeria de Salud de la Junta de Andalucia (PI0458/2013, PS0358/2016, and PI0137/2018), a grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN grant, Fundacio la Marato de TV3 (PI044003), 2017 SGR 1717 from Generalitat de Catalunya, a CICYT grant provided by the Ministerio de Ciencia, Innovacion y Universidades (AGL2016-75329-R), and funds from the European Regional Development Fund (CB06/03 and CB12/03). Food companies Hojiblanca (Lucena, Spain) and Patrimonio Comunal Olivarero (Madrid, Spain) donated extra virgin olive oil, and the Almond Board of California (Modesto, CA, USA), American Pistachio Growers (Fresno, CA, USA), and Paramount Farms (Wonderful Company, LLC, Los Angeles, CA, USA) donated nuts. J.K. was supported by the "FOLIUM" program within the FUTURMed project entitled Talent for the medicine within the future from the Fundacio Institut d'Investigacio Sanitaria Illes Balears. This call was co-financed at 50% with charge to the Operational Program FSE 2014-2020 of the Balearic Islands. This work is partially supported by ICREA under the ICREA Academia programme to J.S.-S.Scope: Plasma fatty acids (FAs) are associated with the development of cardiovascular diseases and metabolic syndrome. The aim of our study is to assess the relationship between fruit and vegetable (F&V) consumption and plasma FAs and their subtypes. Methods and Results: Plasma FAs are assessed in a cross-sectional analysis of a subsample of 240 subjects from the PREDIMED-Plus study. Participants are categorized into four groups of fruit, vegetable, and fat intake according to the food frequency questionnaire. Plasma FA analysis is performed using gas chromatography. Associations between FAs and F&V consumption are adjusted for age, sex, physical activity, bodymass index (BMI), total energy intake, and alcohol consumption. Plasma saturated FAs are lower in groups with high F&V consumption (-1.20 mg cL−1 [95% CI: [-2.22, - 0.18], p-value = 0.021), especially when fat intake is high (-1.74 mg cL−1 [95% CI: [-3.41, -0.06], p-value = 0.042). Total FAs and n-6 polyunsaturated FAs tend to be lower in high consumers of F&V only in the high-fat intake groups. Conclusions: F&V consumption is associated with lower plasma saturated FAs when fat intake is high. These findings suggest that F&V consumption may have different associations with plasma FAs depending on their subtype and on the extent of fat intake.Generalitat de Catalunya FI_B 00256Canadian Institutes of Health Research (CIHR)Consejo Interinstitucional de Ciencia y Tecnologia (CICYT)European Commission AGL2016-75329-RCIBEROBN from the Instituto de Salud Carlos III ISCIII from the Ministerio de Ciencia, Innovacion y Universidades, (AEI/FEDER, UE)Generalitat de Catalunya 2017SGR196CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn)Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS)European Commission 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 PI14/01374Especial Action Project entitled Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grantEuropean Research Council (ERC) European Commission 340918Recercaixa grant 2013ACUP00194Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018Generalitat Valenciana European Commission PROMETEO/2017/017SEMERGEN grant, Fundacio la Marato de TV3 PI044003Generalitat de Catalunya 2017 SGR 1717Ministerio de Ciencia, Innovacion y Universidades AGL2016-75329-R"FOLIUM" program within the FUTURMed project within Fundacio Institut d'Investigacio Sanitaria Illes BalearsICREA under the ICREA Academia programmeThe European Regional Development Fund PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215 PI17/01441 PI17/00508 PI17/01732 PI17/00926 PI19/00781 CB06/03 CB12/03European Commission 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 FPU17/00513 CD17/0012

Circulating carotenoids are associated with favorable lipid and fatty acid profiles in an older population at high cardiovascular risk

Carotenoid intake has been reported to be associated with improved cardiovascular health, but there is little information on actual plasma concentrations of these compounds as biomarkers of cardiometabolic risk. The objective was to investigate the association between circulating plasma carotenoids and different cardiometabolic risk factors and the plasma fatty acid profile. This is a cross-sectional evaluation of baseline data conducted in a subcohort (106 women and 124 men) of an ongoing multi-factorial lifestyle trial for primary cardiovascular prevention. Plasma concentrations of carotenoids were quantified by liquid chromatography coupled to mass spectrometry. The associations between carotenoid concentrations and cardiometabolic risk factors were assessed using regression models adapted for interval-censored variables. Carotenoid concentrations were cross-sectionally inversely associated with serum triglyceride concentrations [-2.79 mg/dl (95% CI: -4.25, -1.34) and -5.15 mg/dl (95% CI: -7.38, -2.93), p-values = 0.0002 and <0.00001 in women and men, respectively], lower levels of plasma saturated fatty acids [-0.09% (95% CI: -0.14, -0.03) and -0.15 % (95% CI: -0.23, -0.08), p-values = 0.001 and 0.0001 in women and men, respectively], and higher levels of plasma polyunsaturated fatty acids [(0.12 % (95% CI: -0.01, 0.25) and 0.39 % (95% CI: 0.19, 0.59), p-values = 0.065 and 0.0001 in women and men, respectively] in the whole population. Plasma carotenoid concentrations were also associated with higher plasma HDL-cholesterol in women [0.47 mg/dl (95% CI: 0.23, 0.72), p-value: 0.0002], and lower fasting plasma glucose in men [-1.35 mg/dl (95% CI: -2.12, -0.59), p-value: 0.001]. Keywords: Mediterranean diet; PREDIMED-plus study; cardiovascular health; liquid chromatography; mass spectrometry; plasma carotenoids

Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design

Introduction: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Methods: Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. Discussion: This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain.The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL, by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571), by the Conselleria de Sanitat of the Generalitat Valenciana (AP 061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country by European Commission grants FOOD-CT- 2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the The Catalan Government DURSI grant 2009SGR1489

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Síndrome de osteoporosis con pseudoglioma

Pseudoglioma osteoporosis syndrome in an autosomal recessive disease caused by a defect in the gene LRP5 located. It is an ocular with osteogenesis imperfecta. We report the case of a 9-year-old with motor retardation, blindness, and generalized aches, who also suffered from two broken bones when he was 4 years old. The scan shows pondoestatural delay, microphthalmia, cataracts, walleye bilateral entropion in both eyes and microcephaly. The study objective radiological osteopenia and MRI brain important one enlarged cisterna magna, as a sign not described in this syndrome. The genetic study shows an alteration of the gene LRP5. Treatment with bisphosphonates and growth hormone has been satisfactory.El síndrome osteoporosis con pseudoglioma en una enfermedad autosómica recesiva debida a un defecto situado en el gen LRP5. Se trata de una osteogénesis imperfecta con afectación ocular. Se presenta el caso de una paciente de 9 años de edad, con retraso motor, ceguera, dolores generalizados y dos fracturas óseas padecidas durante la lactancia y a los 4 años de edad. La exploración muestra retraso pondoestatural, microftalmia, cataratas, leucoma bilateral, entropión de ambos ojos y microcefalia. El estudio radiológico objetiva osteopenia importante y la RMN cerebral una cisterna magna aumentada de tamaño, como signo no descrito en este síndrome. El estudio genético muestra una alteración del gen LRP5. El tratamiento con bifosfonatos y hormona de crecimiento ha sido satisfactorio