1,3-Bis(3-carboxypropyl)-1H-imidazole

The use of γ-aminobutyric acid (GABA) as a starting material in a multicomponent reaction has resulted in the preparation of the zwitterionic 1,3-bis(3-carboxypropyl)imidazole (bcpim). The synthesis of this imidazole derivative in a one-pot procedure with stoichiometric amounts of the corresponding reagents (formaldehyde, glyoxal, and GABA in a 1:1:2 ratio) has resulted in a straightforward and effective methodology, meaning a significant improvement from a sustainable point of view.This research was funded by Ministerio de Ciencia, Innovación y Universidades (grant number PGC2018-096616-B-I00), Ministerio de Ciencia e Innovación (PID2021-127332NB-I00), Generalitat Valenciana (grant number AICO/2021/013), and the University of Alicante (grant number VIGROB-316)

Transcriptomic differences in MSA clinical variants

Background: Multiple system atrophy (MSA) is a rare oligodendroglial synucleinopathy of unknown etiopathogenesis including two major clinical variants with predominant parkinsonism (MSA-P) or cerebellar dysfunction (MSA-C). Objective: To identify novel disease mechanisms we performed a blood transcriptomic study investigating differential gene expression changes and biological process alterations in MSA and its clinical subtypes. Methods: We compared the transcriptome from rigorously gender and age-balanced groups of 10 probable MSA-P, 10 probable MSA-C cases, 10 controls from the Catalan MSA Registry (CMSAR), and 10 Parkinson Disease (PD) patients. Results: Gene set enrichment analyses showed prominent positive enrichment in processes related to immunity and inflammation in all groups, and a negative enrichment in cell differentiation and development of the nervous system in both MSA-P and PD, in contrast to protein translation and processing in MSA-C. Gene set enrichment analysis using expression patterns in different brain regions as a reference also showed distinct results between the different synucleinopathies. Conclusions: In line with the two major phenotypes described in the clinic, our data suggest that gene expression and biological processes might be differentially affected in MSA-P and MSA-C. Future studies using larger sample sizes are warranted to confirm these results

Transplantation of mesenchymal stem cells exerts a greater long-term effect than bone marrow mononuclear cells in a chronic myocardial infarction model in rat

The aim of this study is to assess the long-term effect of mesenchymal stem cells (MSC) transplantation in a rat model of chronic myocardial infarction (MI) in comparison with the effect of bone marrow mononuclear cells (BM-MNC) transplant. Five weeks after induction of MI, rats were allocated to receive intramyocardial injection of 106 GFP-expressing cells (BM-MNC or MSC) or medium as control. Heart function (echocardiography and 18F-FDG-microPET) and histological studies were performed 3 months after transplantation and cell fate was analyzed along the experiment (1 and 2 weeks and 1 and 3 months). The main findings of this study were that both BM-derived populations, BM-MNC and MSC, induced a long-lasting (3 months) improvement in LVEF (BM-MNC: 26.61 ± 2.01% to 46.61 ± 3.7%, p < 0.05; MSC: 27.5 ± 1.28% to 38.8 ± 3.2%, p < 0.05) but remarkably, only MSC improved tissue metabolism quantified by 18FFDG uptake (71.15 ± 1.27 to 76.31 ± 1.11, p < 0.01), which was thereby associated with a smaller infarct size and scar collagen content and also with a higher revascularization degree. Altogether, results show that MSC provides a long-term superior benefit than whole BM-MNC transplantation in a rat model of chronic MI

Normalization of sphingomyelin levels by 2-hydroxyoleic acid induces autophagic cell death of SF767 cancer cells

The very high mortality rate of gliomas reflects the unmet therapeutic need associated with this type of brain tumor. We have discovered that the plasma membrane fulfills a critical role in the propagation of tumorigenic signals, whereby changes in membrane lipid content can either activate or silence relevant pathways. We have designed a synthetic fatty acid, 2-hydroxyoleic acid (2OHOA), that specifically activates sphingomyelin synthase (SGMS), thereby modifying the lipid content of cancer cell membranes and restoring lipid levels to those found in normal cells. In reverting, the structure of the membrane by activating SGMS, 2OHOA inhibits the RAS-MAPK pathway, which in turn fails to activate the CCND (Cyclin D)-CDK4/CDK6 and PI3K-AKT1 pathways. The overall result in SF767 cancer cells, a line that is resistant to apoptosis, is the sequential induction of cell cycle arrest, cell differentiation and autophagy. Such effects are not observed in normal cells (MRC-5) and thus, this specific activation of programmed cell death infers greater efficacy and lower toxicity to 2OHOA than that associated with temozolomide (TMZ), the reference drug for the treatment of glioma

Manejo del pastizal y su influencia en la respuesta económica de rebaños de cría.

Se estudió la influencia de los principales componentes del manejo del pastizal en la respuesta económica de rebaños de cría de la Empresa Genética Rescate de Sanguily, desde enero de 2012 a diciembre de 2014. Se seleccionaron seis unidades de cría de la granja  Ricardo Flores, perteneciente a esta empresa, ubicada en el Municipio de Jima-guayú, provincia Camagüey, Cuba. Se tomaron variables sobre la situación de los pastizales y los recursos forrajeros en general y para determinar los componentes fundamentales que determinan la variabilidad de las unidades de cría. Se utilizó el análisis de  componentes principales, seleccionando aquellos componentes que presentaban un autovalor superior a la unidad y dentro de cada componente principal aquellas variables con cargas superiores a 0,60; se pudo definir que entre los elementos del manejo de los pastizales en unidades de cría, destacan el área de forraje, de pastos cultivados y pastos naturales, que explican más del 40% de la varianza entre las unidades del estudio. El balance forrajero en las entidades es negativo, como resultado de la pobre atención agrotécnica a los pastiza les; aún así, la relación gastos-ingresos es positiva, con ganancias brutas que oscilan entre 2 500 y 17 600 CUP, lo que obedece a los bajos costos por concepto de alimentación. Se requiere priorizar las actividades y recursos relacionados con la agrotécnia de los pastos y forrajes, así como el completamiento de áreas de forrajes.Pastureland Management and Influence on the Economic Response of Breeding Herds.ABSTRACTThe influence of the main pastureland components on the economic response of breeding herds at the  Rescate de Sanguily Enterprise was studied, from January 2012 to December 2014. Six breeding units from  Ricardo Flores unit were chosen, in the municipality of  Jimaguayú, province of Camagüey, Cuba. Variables of pastureland, and forage resources in general were used. To determine the main components that led to variability of breeding units, a Prin-cipal Component Analysis was performed;  components with values above the unit were selected. Stocking rates va-riables,  over 0.60, were chosen too.  The elements related with pastureland management in  breeding units were de-fined (forage area with native and cultivated grass), which explain the more than 40  % variance in all the units under the study. Forage balance is negative in the units, as a result of poor agrotechnical management of grasslands; however, the expenses-income ratio is positive (between CUP $2 500 and$17 600), caused by the low feeding costs. Activities and resources linked to pasture and forage agrotechniques must be prioritized, along with the completion of forage areas

Prospects for macroscopic dark matter detection at space-based and suborbital experiments

We compare two different formalisms for modeling the energy deposition of macroscopically sized/massive quark nuggets (a.k.a. macros) in the Earth's atmosphere. We show that for a reference mass of 1 g, there is a discrepancy in the macro luminosity of about 14 orders of magnitude between the predictions of the two formalisms. Armed with our finding we estimate the sensitivity for macro detection at space-based (Mini-EUSO and POEMMA) and suborbital (EUSO-SPB2) experiments.Comment: 5 pages revtex, 3 figure

Lung Retransplantation with Positive Crossmatch in Primary Lung Transplantation Complicated by Antibody-Mediated Rejection

La hipertensión arterial pulmonar (HAP) representa el 2,6% de los trasplantes pulmonares (TP), con una mediana de supervivencia condicional(desde los 30 días del TP) de 9,8 años. Son frecuentes, el rechazo celular agudo (ACR) y la disfunción crónica del injerto (CLAD),mientras que es infrecuente el rechazo mediado por anticuerpos (AMR). El retrasplante pulmonar (RTP) constituye el 4% del TP mundial,debido a complicaciones en la vía aérea, disfunción primaria del injerto, ACR y CLAD. Mujer de 22 años, portadora de HAP idiopática(HAPI) desde el año 2013, trasplantada bipulmonar (TBP) en enero de 2018. A los 16 meses presentó neumonía adquirida en la comunidad.En una internación posterior, presentó ACR y a pesar de pulsos de metilprednisolona, progresó a requerimientos de cánula de altoflujo y ventilación mecánica no invasiva hospitalaria, caída del VEF1, y tomografía de tórax con vidrio esmerilado difuso y engrosamientoirregular reticular del intersticio subpleural; interpretándose como CLAD a predominio de síndrome de bronquiolitis obliterante (BOS),con presencia de anticuerpos específicos contra el donante (DSA). En enero de 2020 se realizó nuevo TP y ante cross-match positivo, serealizó plasmaféresis y reposición de IgG. Al mes del egreso, no se observaron signos de rechazo en control de biopsias transbronquiales.Entre 2 y 10% de los pacientes con indicación primaria de TP por HAPI son sometidos a retrasplante pulmonar (RTP). La presencia deDSA y el miss-match de HLA, no son contraindicaciones para el RTP.Pulmonary arterial hypertension (PAH) represents 2.6% of lung transplantations (LT), with a conditional median survival (from 30 days after LT) of 9.8 years. Acute cellular rejection (ACR) and chronic lung allograft dysfunction (CLAD) are common; whereas the antibody-mediated rejection (AMR) is not. Lung retransplantation (LR) accounts for 4% of global LTs for complications in the airways, primary allograft dysfunction, ACR and CLAD. 22-year-old woman with idiopathic PAH (IPAH) since 2013, who underwent a double-lung transplantation (DLT) in January 2018. 16 months after transplantation she presented community-acquired pneumonia. During a subsequent hospitalization, she presented ACR. Despite the fact that she received pulse methylprednisolone, she required high-flow cannula therapy and hospital non-invasive mechanical ventilation; the FEV1 was reduced and she underwent a chest tomography with diffuse ground glass opacities and irregular reticular thickening of the subpleural interstitium; interpreting the predominance of BOS (bronchiolitis obliterans syndrome) as CLAD, with presence of donor-specific antibodies (DSA). In January 2020, she received a new DLT and due to a positive crossmatch, she was treated with plasmapheresis and IgG replacement. One month after hospital discharge, no signs of rejection were observed at the BTB (bone-patellar tendon-bone) control. Between 2 to 10% of patients with primary indication of LT for IPAH are subjected to lung retransplantation (LR). The presence of DSA and HLA (human leucocyte antigen) mismatch aren’t contraindications to LR.Fil: Calderón Soriano, Juan C.. Fundación Favaloro; ArgentinaFil: Nazzo, María V.,. Fundación Favaloro; ArgentinaFil: Pérez Páez, Martha I.. Fundación Favaloro; ArgentinaFil: Virhuez, Yblin. Fundación Favaloro; ArgentinaFil: Balcazar, Jonathan. Fundación Favaloro; ArgentinaFil: Vicente, Luis. Fundación Favaloro; ArgentinaFil: Ahumada, Rosalía. Fundación Favaloro; ArgentinaFil: Osses, Juan M.. Fundación Favaloro; ArgentinaFil: Vigliano, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Bertolotti, Alejandro Mario. Fundación Favaloro; ArgentinaFil: Caneva, Jorge O.. Fundación Favaloro; Argentin

Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts

[Background] Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia.[Methods] A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3).[Results] Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03–6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04–4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12–0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08–4.24, p = 0.02).[Conclusions] Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms.This study was funded by a research grant from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III [FIS PI15/00744], European Regional Development Fund (ERDF); CGV is a recipient of an INTENSIFICACIÓ Grant from the “Strategic plan for research and innovation in health-PERIS 2016-2020” and forms part of the Fungi CLINIC Research group (AGAUR-Project 2017SGR1432 of the Catalan Health Agency)

Older age does not influence CD4 cell recovery in HIV-1 infected patients receiving Highly Active Anti Retroviral Therapy

BACKGROUND: Diagnosis of HIV infection is recently occurring with increasing frequency in middle-aged and in older individuals. As HAART became available, a minimal beneficial effect on immunological outcome in older in respect of younger subjects has been reported. In fact, both the intensity and the rapidity of the immunological response appeared to be reduced in elderly subjects. On the contrary, only few reports have indicated a similar immunological outcome both in older and younger HIV-positive subjects. Interestingly, older age did not seem to significantly affect the long-term virological outcome of HAART treated subjects. METHODS: To characterise epidemiological and clinical features of older HIV+ subjects, a prospective case-control study was performed: 120 subjects ≥ 50 and 476 between 20 and 35 years were initially compared. Subsequently, to better define the impact of HAART on their viro-immunological response, 81 older were compared with 162 younger subjects. RESULTS: At baseline cases presented significantly lower TCD4+ cell number and were more frequently affected by comorbid conditions. Under HAART a statistically significant increase in TCD4+ cell number was observed in cases and controls. At multivariate analysis, there was no statistically significant difference between cases and controls regarding viro-immunological response. CONCLUSIONS: Although older subjects present a more severe HIV infection, they can achieve, under HAART, the same viro-immunological success as the younger individuals