The role of cell-free DNA measured by a fluorescent test in the management of isolated traumatic head injuries

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. In this study a new method to measure cell free DNA (CFD) for the management of TBI is tested. Our hypothesis was that CFD concentrations correlate to the magnitude of brain damage, and may predict the outcome of injured patients. METHODS: Twenty eight patients with isolated head injury were enrolled. Their demographic and clinical data were recorded. CFD levels were determined in patients' sera samples by a direct fluorescence method developed in our laboratory. RESULTS: Mean admission CFD values were lower in patients with mild TBI compared to severe injury (760 ± 340 ng/ml vs. 1600 ± 2100 ng/ml, p = 0.03), and in patients with complete recovery upon discharge compared to patients with disabilities (680 ± 260 ng/ml vs. 2000 ± 2300 ng/ml, p = 0.003). Patients with high CFD values had a relative risk to require surgery of 1.5 (95% CI 0.83 to 2.9) a relative risk to have impaired outcome on discharge of 2.8 (95% CI 0.75 – 10), and a longer length of stay (12 ± 13 days vs. 3.4 ± 4.8 days, p = 0.02). CFD values did not correlate with CT scan based grading. CONCLUSIONS: CFD levels may be used as a marker to assess the severity of TBI and to predict the prognosis. Its use should be considered as an additional tool along with currently used methods or as a surrogate for them in limited resources environment

Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium

Liver X receptors (LXRs) are li-gand-dependent transcription factors activated by cholesterol metabolites. These receptors induce a suite of target genes required for de novo synthesis of triglycerides and cholesterol transport in many tissues. Two different isoforms, LXRβ and LXRβ, have been well characterized in liver, adipocytes, macrophages, and intestinal epithelium among others, but their contribution to cholesterol and fatty acid efflux in the lactating mammary epithelium is poorly understood. We hypothesize that LXR regulates lipogenesis during milk fat production in lactation. Global mRNA analysis of mouse mammary epithelial cells (MECs) revealed multiple LXR/RXR targets upregulated sharply early in lactation compared with midpregnancy. LXRβ is the primary isoform, and its protein levels increase throughout lactation in MECs. The LXR agonist GW3965 markedly induced several genes involved in cholesterol transport and lipogenesis and enhanced cytoplasmic lipid droplet accumulation in the HC11 MEC cell line. Importantly, in vivo pharmacological activation of LXR increased the milk cholesterol percentage and induced sterol regulatory element-binding protein 1c (Srebp1c) and ATP-binding cassette transporter a7 (Abca7) expression in MECs. Cumulatively, our findings identify LXRβ as an important regulator of cholesterol incorporation into the milk through key nodes of de novo lipogenesis, suggesting a potential therapeutic target in women with difficulty initiating lactation.Fil: Grinman, Diego Yair. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Careaga Quiroga, Valeria Pilar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wellberg, Elizabeth A.. University of Colorado; Estados UnidosFil: Dansey, Maria Virginia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kordon, Edith Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Anderson, Steven M.. University of Colorado; Estados UnidosFil: Maier, Marta Silvia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Burton, Gerardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: MacLean, Paul S.. University of Colorado; Estados UnidosFil: Rudolph, Michael C.. University of Colorado; Estados UnidosFil: Pecci, Adali. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

The role of cell-free DNA measured by a fluorescent test in the management of isolated traumatic head injuries.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. In this study a new method to measure cell free DNA (CFD) for the management of TBI is tested. Our hypothesis was that CFD concentrations correlate to the magnitude of brain damage, and may predict the outcome of injured patients. METHODS: Twenty eight patients with isolated head injury were enrolled. Their demographic and clinical data were recorded. CFD levels were determined in patients sera samples by a direct fluorescence method developed in our laboratory. RESULTS: Mean admission CFD values were lower in patients with mild TBI compared to severe injury (760 ± 340 ng/ml vs. 1600 ± 2100 ng/ml, p = 0.03), and in patients with complete recovery upon discharge compared to patients with disabilities (680 ± 260 ng/ml vs. 2000 ± 2300 ng/ml, p = 0.003). Patients with high CFD values had a relative risk to require surgery of 1.5 (95% CI 0.83 to 2.9) a relative risk to have impaired outcome on discharge of 2.8 (95% CI 0.75 - 10), and a longer length of stay (12 ± 13 days vs. 3.4 ± 4.8 days, p = 0.02). CFD values did not correlate with CT scan based grading. CONCLUSIONS: CFD levels may be used as a marker to assess the severity of TBI and to predict the prognosis. Its use should be considered as an additional tool along with currently used methods or as a surrogate for them in limited resources environment

The role of cell-free DNA measured by a fluorescent test in the management of isolated traumatic head injuries.

BackgroundTraumatic brain injury (TBI) is a major cause of death and disability. In this study a new method to measure cell free DNA (CFD) for the management of TBI is tested. Our hypothesis was that CFD concentrations correlate to the magnitude of brain damage, and may predict the outcome of injured patients.MethodsTwenty eight patients with isolated head injury were enrolled. Their demographic and clinical data were recorded. CFD levels were determined in patients' sera samples by a direct fluorescence method developed in our laboratory.ResultsMean admission CFD values were lower in patients with mild TBI compared to severe injury (760 ± 340 ng/ml vs. 1600 ± 2100 ng/ml, p = 0.03), and in patients with complete recovery upon discharge compared to patients with disabilities (680 ± 260 ng/ml vs. 2000 ± 2300 ng/ml, p = 0.003). Patients with high CFD values had a relative risk to require surgery of 1.5 (95% CI 0.83 to 2.9) a relative risk to have impaired outcome on discharge of 2.8 (95% CI 0.75 - 10), and a longer length of stay (12 ± 13 days vs. 3.4 ± 4.8 days, p = 0.02). CFD values did not correlate with CT scan based grading.ConclusionsCFD levels may be used as a marker to assess the severity of TBI and to predict the prognosis. Its use should be considered as an additional tool along with currently used methods or as a surrogate for them in limited resources environment

Photophysics of Xanthene Dyes at High Concentrations in Solid Environments: Charge Transfer Assisted Triplet Formation

The photophysical behavior of two xanthene dyes, Eosin Y and Phloxine B, included in microcrystalline cellulose particles is studied in a wide concentration range, with emphasis on the effect of dye concentration on fluorescence and triplet quantum yields. Absolute fluorescence quantum yields in the solid-state were determined by means of diffuse reflectance and steady-state fluorescence measurements, whereas absolute triplet quantum yields were obtained by laser-induced optoacoustic spectroscopy and their dependence on dye concentration was confirmed by diffuse reflectance laser flash photolysis and time-resolved phosphorescence measurements. When both quantum yields are corrected for reabsorption and reemission of radiation, ΦF values decrease strongly on increasing dye concentration, while a less pronounced decay is observed for ΦT . Fluorescence concentration quenching is attributed to the formation of dye aggregates or virtual traps resulting from molecular crowding. Dimeric traps are however able to generate triplet states. A mechanism based on the intermediacy of charge-transfer states is proposed and discussed. Calculation of parameters for photoinduced electron transfer between dye molecules within the traps evidences the feasibility of the proposed mechanism. Results demonstrate that photoactive energy traps, capable of yielding dye triplet states, can be formed even in highly-concentrated systems with random dye distributions.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada