Formation of heterokaryons by fusion of isolated hyphal tips on solid medium in petri plates

Formation of heterokaryons by fusion of isolated hyphal tips on solid medium in petri plate

Photodynamic effects of acridine orange an Neurospora sitaphila

Photodynamic effects of acridine orang

Artroplastia unicompartimental de rodilla sin cementar: indicaciones y resultados

Desde abril de 1987 hasta octubre de 1990, 100 pacientes (81 mujeres y 19 hombres) de 69 años de edad media fueron intervenidos mediante artroplastia unicompartmental de rodilla. El tiempo medio de seguimiento fue de 28 meses (rango: 12-48). La artroplastia fue indicada por osteoartrosis unicompartimental en 91 casos, necrosis aséptica femoral en 8 y destrucción post-traumática en 1. El implante utilizado era de tipo no constreñido y fijación sin cemento. En los primeros 12 meses de evolución, murieron 4 pacientes y otros 2 casos precisaron de reintervención, uno por aflojamiento de componente tibial y otro por luxación de ambos componentes. De los 94 pacientes restantes, 90 quedaron asintomáticos o referían mínimo dolor tras la intervención. La valoración funcional global en la escala de Hungerford fue de 63 puntos en el estudio preoperatorio y de 93 en la revisión postoperatoria, lo que indica un excelente resultado. Radiológicamente, sólo se objetivó un caso de aflojamiento del implante femoral. En 90 casos, la osteointegración a nivel tibial fue completa. Tras 2 años de seguimiento, la supervivencia del implante fue del 98%.From April 1987 to October 1990, an uncemented unicompartmental knee arthroplasty was performed in 100 patients (81 women, 19 men) with a mean age of 69 years. The mean follow-up period was 28 months (range, 12-48). The indication for arthroplasty was unicompartmental osteoarthritis in 91 cases, femoral necrosis in 8, and post-traumatic femoral destruction in one. The implant used was an uncemented non-constrained design. Four patients died during the first 12 months after surgery. Two patients were reoperated; one had loosening of the tibial component and the other showed dislocation of the femoral implant backwards the tibial component. In this last patient both components were well fixed showing no signs of loosening. Out of the 94 remained cases, 90 were either asymptomatic or complain of very slight pain. Functional assessment according to Hungerford disclosed 63 points before surgery and 93 at review, indicating an excellent functional outcome. In the radiographic study, only one case who was reoperated showed loosening of the tibial component. In 90 of the 94 patients studied, and apparent good bone ingrowth was observed at the tibial component. After 2-year follow-up, the survival of the implant was found to be 98%

Short-term effects of simulated microgravity on morphology and gene expression in human breast cancer cells

Introduction Microgravity has been shown to impose various effects on breast cancer cells. We exposed human breast cancer cells to simulated microgravity and studied morphology and alterations in gene expression. Materials and methods Human breast cancer cells were exposed to simulated microgravity in a random positioning machine (RPM) for 24 h. Morphology was observed under light microscopy, and gene alteration was studied by qPCR. Results After 24 h, formation of three-dimensional structures (spheroids) occurred. BRCA1 expression was significantly increased (1.9×, p < 0.05) in the adherent cells under simulated microgravity compared to the control. Expression of KRAS was significantly decreased (0.6×, p < 0.05) in the adherent cells compared to the control. VCAM1 was significantly upregulated (6.6×, 2.0×, p < 0.05 each) in the adherent cells under simulated microgravity and in the spheroids. VIM expression was significantly downregulated (0.45×, 0.44×, p < 0.05 each) in the adherent cells under simulated microgravity and in the spheroids. There was no significant alteration in the expression of MAPK1, MMP13, PTEN, and TP53. Conclusions Simulated microgravity induces spheroid formation in human breast cancer cells within 24 h and alters gene expression toward modified adhesion properties, enhanced cell repair, and phenotype preservation. Further insights into the underlying mechanisms could open up the way toward new therapies

On the Power of Robust Solutions in Two-Stage Stochastic and Adaptive Optimization Problems

We consider a two-stage mixed integer stochastic optimization problem and show that a static robust solution is a good approximation to the fully adaptable two-stage solution for the stochastic problem under fairly general assumptions on the uncertainty set and the probability distribution. In particular, we show that if the right-hand side of the constraints is uncertain and belongs to a symmetric uncertainty set (such as hypercube, ellipsoid or norm ball) and the probability measure is also symmetric, then the cost of the optimal fixed solution to the corresponding robust problem is at most twice the optimal expected cost of the two-stage stochastic problem. Furthermore, we show that the bound is tight for symmetric uncertainty sets and can be arbitrarily large if the uncertainty set is not symmetric. We refer to the ratio of the optimal cost of the robust problem and the optimal cost of the two-stage stochastic problem as the stochasticity gap. We also extend the bound on the stochasticity gap for another class of uncertainty sets referred to as positive. If both the objective coefficients and right-hand side are uncertain, we show that the stochasticity gap can be arbitrarily large even if the uncertainty set and the probability measure are both symmetric. However, we prove that the adaptability gap (ratio of optimal cost of the robust problem and the optimal cost of a two-stage fully adaptable problem) is at most four even if both the objective coefficients and the right-hand side of the constraints are uncertain and belong to a symmetric uncertainty set. The bound holds for the class of positive uncertainty sets as well. Moreover, if the uncertainty set is a hypercube (special case of a symmetric set), the adaptability gap is one under an even more general model of uncertainty where the constraint coefficients are also uncertain.National Science Foundation (U.S.) (NSF Grant DMI-0556106)National Science Foundation (U.S.) (NSF Grant EFRI-0735905

A Geometric Characterization of the Power of Finite Adaptability in Multistage Stochastic and Adaptive Optimization

In this paper, we show a significant role that geometric properties of uncertainty sets, such as symmetry, play in determining the power of robust and finitely adaptable solutions in multistage stochastic and adaptive optimization problems. We consider a fairly general class of multistage mixed integer stochastic and adaptive optimization problems and propose a good approximate solution policy with performance guarantees that depend on the geometric properties of the uncertainty sets. In particular, we show that a class of finitely adaptable solutions is a good approximation for both the multistage stochastic and the adaptive optimization problem. A finitely adaptable solution generalizes the notion of a static robust solution and specifies a small set of solutions for each stage; the solution policy implements the best solution from the given set, depending on the realization of the uncertain parameters in past stages. Therefore, it is a tractable approximation to a fully adaptable solution for the multistage problems. To the best of our knowledge, these are the first approximation results for the multistage problem in such generality. Moreover, the results and the proof techniques are quite general and also extend to include important constraints such as integrality and linear conic constraints.National Science Foundation (U.S.) (Grant EFRI-0735905

Pathways Regulating Spheroid Formation of Human Follicular Thyroid Cancer Cells under Simulated Microgravity Conditions: A Genetic Approach

Microgravity induces three-dimensional (3D) growth in numerous cell types. Despite substantial efforts to clarify the underlying mechanisms for spheroid formation, the precise molecular pathways are still not known. The principal aim of this paper is to compare static 1g-control cells with spheroid forming (MCS) and spheroid non-forming (AD) thyroid cancer cells cultured in the same flask under simulated microgravity conditions. We investigated the morphology and gene expression patterns in human follicular thyroid cancer cells (UCLA RO82-W-1 cell line) after a 24 h-exposure on the Random Positioning Machine (RPM) and focused on 3D growth signaling processes. After 24 h, spheroid formation was observed in RPM-cultures together with alterations in the F-actin cytoskeleton. qPCR indicated more changes in gene expression in MCS than in AD cells. Of the 24 genes analyzed VEGFA, VEGFD, MSN, and MMP3 were upregulated in MCS compared to 1g-controls, whereas ACTB, ACTA2, KRT8, TUBB, EZR, RDX, PRKCA, CAV1, MMP9, PAI1, CTGF, MCP1 were downregulated. A pathway analysis revealed that the upregulated genes code for proteins, which promote 3D growth (angiogenesis) and prevent excessive accumulation of extracellular proteins, while genes coding for structural proteins are downregulated. Pathways regulating the strength/rigidity of cytoskeletal proteins, the amount of extracellular proteins, and 3D growth may be involved in MCS formation

Metabolic View on Human Healthspan: A Lipidome-Wide Association Study.

As ageing is a major risk factor for the development of non-communicable diseases, extending healthspan has become a medical and societal necessity. Precise lipid phenotyping that captures metabolic individuality could support healthspan extension strategies. This study applied 'omic-scale lipid profiling to characterise sex-specific age-related differences in the serum lipidome composition of healthy humans. A subset of the COmPLETE-Health study, composed of 73 young (25.2 ± 2.6 years, 43% female) and 77 aged (73.5 ± 2.3 years, 48% female) clinically healthy individuals, was investigated, using an untargeted liquid chromatography high-resolution mass spectrometry approach. Compared to their younger counterparts, aged females and males exhibited significant higher levels in 138 and 107 lipid species representing 15 and 13 distinct subclasses, respectively. Percentage of difference ranged from 5.8% to 61.7% (females) and from 5.3% to 46.0% (males), with sphingolipid and glycerophophospholipid species displaying the greatest amplitudes. Remarkably, specific sphingolipid and glycerophospholipid species, previously described as cardiometabolically favourable, were found elevated in aged individuals. Furthermore, specific ether-glycerophospholipid and lyso-glycerophosphocholine species displayed higher levels in aged females only, revealing a more favourable lipidome evolution in females. Altogether, age determined the circulating lipidome composition, while lipid species analysis revealed additional findings that were not observed at the subclass level

Effect of an eight-week high-intensity interval training programme on circulating sphingolipid levels in middle-aged adults at elevated cardiometabolic risk (SphingoFIT)-Protocol for a randomised controlled exercise trial.

Evidence indicates that sphingolipid accumulation drives complex molecular alterations promoting cardiometabolic diseases. Clinically, it was shown that sphingolipids predict cardiometabolic risk independently of and beyond traditional biomarkers such as low-density lipoprotein cholesterol. To date, little is known about therapeutic modalities to lower sphingolipid levels. Exercise, a powerful means to prevent and treat cardiometabolic diseases, is a promising modality to mitigate sphingolipid levels in a cost-effective, safe, and patient-empowering manner. This randomised controlled trial will explore whether and to what extent an 8-week fitness-enhancing training programme can lower serum sphingolipid levels of middle-aged adults at elevated cardiometabolic risk (n = 98, 50% females). The exercise intervention will consist of supervised high-intensity interval training (three sessions weekly), while the control group will receive physical activity counselling based on current guidelines. Blood will be sampled early in the morning in a fasted state before and after the 8-week programme. Participants will be provided with individualised, pre-packaged meals for the two days preceding blood sampling to minimise potential confounding. An 'omic-scale sphingolipid profiling, using high-coverage reversed-phase liquid chromatography coupled to tandem mass spectrometry, will be applied to capture the circulating sphingolipidome. Maximal cardiopulmonary exercise tests will be performed before and after the 8-week programme to assess patient fitness changes. Cholesterol, triglycerides, glycated haemoglobin, the homeostatic model assessment for insulin resistance, static retinal vessel analysis, flow-mediated dilatation, and strain analysis of the heart cavities will also be assessed pre- and post-intervention. This study shall inform whether and to what extent exercise can be used as an evidence-based treatment to lower circulating sphingolipid levels. The trial was registered on www.clinicaltrials.gov (NCT06024291) on August 28, 2023

Atopic conditions and brain tumor risk in children and adolescents—an international case-control study (CEFALO)

In this study, atopic conditions were not associated with risk of brain tumors in children and adolescents or of glioma in particular. Results are not consistent with findings for adult glioma, possibly explained by a different distribution of histological subtypes. Only a few studies on atopic conditions and pediatric brain tumors are currently available, and the evidence is conflictin