19 research outputs found
Simple methodology for the quantitative analysis of fatty acids in human red blood cells
In the last years, there has been an increasing
interest in evaluating possible relations between fatty acid
(FA) patterns and the risk for chronic diseases. Due to the
long life span (120 days) of red blood cells (RBCs), their
FA profile reflects a longer term dietary intake and was
recently suggested to be used as an appropriate biomarker
to investigate correlations between FA metabolism and diseases.
Therefore, the aim of this work was to develop and
validate a simple and fast methodology for the quantification
of a broad range of FAs in RBCs using gas chromatography
with flame ionization detector, as a more common
and affordable equipment suitable for biomedical and
nutritional studies including a large number of samples. For
this purpose, different sample preparation protocols were
tested and compared, including a classic two-step method
(Folch method) with modifications and different one-step methods, in which lipid extraction and derivatization were
performed simultaneously. For the one-step methods, different
methylation periods and the inclusion of a saponification
reaction were evaluated. Differences in absolute FA
concentrations were observed among the tested methods,
in particular for some metabolically relevant FAs such as
trans elaidic acid and eicosapentaenoic acid. The one-step
method with saponification and 60 min of methylation time
was selected since it allowed the identification of a higher
number of FAs, and was further submitted to in-house validation.
The proposed methodology provides a simple, fast
and accurate tool to quantitatively analyse FAs in human
RBCs, useful for clinical and nutritional studies.This work received financial support from the
European Union (FEDER funds through COMPETE) and National
Funds (FCT, Fundação para a Ciência e Tecnologia) through project
PTDC/SAU-ENB/116929/2010 and EXPL/EMS-SIS/2215/2013.
ROR acknowledges PhD scholarship SFRH/BD/97658/2013 attributed
by FCT (Fundação para a Ciência e Tecnologia).info:eu-repo/semantics/publishedVersio
Regioisomeric and substituent effects upon the outcome of the reaction of 1-borodienes with nitrosoarene compounds
A study of the reactivity of 1-borodienes with nitrosoarene compounds has been carried out showing an outcome that differs according to the hybridization state of the boron moiety. Using an sp2 boron substituent, a one-pot hetero-Diels–Alder/ring contraction cascade occurred to afford N-arylpyrroles with low to good yields depending on the electronic properties of the substituents on the borodiene, whereas an sp3 boron substituent led to the formation of stable boro-oxazines with high regioselectivity in most of the cases, in moderate to good yields. 1H and 11B NMR studies on two boro-oxazine regioisomers showed that selective deprotection can be performed. Formation of either the pyrrole or the furan derivative is pH- and regioisomer-structure-dependent. The results obtained, together with previous B3LYP calculations, support mechanistic proposals which suggest that pyrrole, or furan, formation proceeds via oxazine formation, followed by a boryl rearrangement and an intramolecular addition–elimination sequence
Regioisomeric and Substituent Effects upon the Outcome of the Reaction of 1-Borodienes with Nitrosoarene Compounds
A consistent frame for sensitivity filtering and the vertex assigned morphing of optimal shape
How does feeding organic broilers high levels of alfalfa silage affect the meat quality?
Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients
DDD: Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. While Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the hazard associated with liver transplantation in HCC (HALTHCC) in an international cohort. From 2002-2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-LT levels of alpha feto-protein, model for end stage liver disease sodium score, and tumor burden score was recalibrated amongst a randomly selected cohort (n=1,021) and validated in the remainder (n=3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion(VI) and poorly differentiated component(PDC) increased with increasing HALTHCC score. The lowest risk patients (HALTHCC 0-5) had lower rates of VI and PDC than the highest risk patients (HALTHCC>35) (VI:7.7%[1.2-14.2] vs 70.6%[48.3-92.9] and PDC:4.6%[0.1-9.8%] vs 47.1%[22.6-71.5]; P<0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (C-index=0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C-index=0.71) and overall survival (C-index=0.63). CONCLUSION: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre-LT risk amongst candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted. This article is protected by copyright. All rights reserved
Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients
Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. Although Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma (HALTHCC), in an international cohort. From 2002 to 2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-LT levels of alpha-fetoprotein, Model for End-Stage Liver Disease Sodium score, and tumor burden score was recalibrated among a randomly selected cohort (n = 1,021) and validated in the remainder (n = 3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion (VI) and poorly differentiated component (PDC) increased with increasing HALTHCC score. The lowest-risk patients (HALTHCC 0-5) had lower rates of VI and PDC than the highest-risk patients (HALTHCC > 35) (VI, 7.7%[ 1.2-14.2] vs. 70.6% [48.3-92.9] and PDC:4.6% [0.1%-9.8%] vs. 47.1% [22.6-71.5]; P < 0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (OS; C-index = 0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C-index = 0.71) and OS (C-index = 0.63). Conclusion: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre-LT risk among candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted