Pressurized Extraction as an Opportunity to Recover Antioxidants from Orange Peels: Heat treatment and Nanoemulsion Design for Modulating Oxidative Stress.

Orange peel by-products generated in the food industry are an important source of value-added compounds that can be potentially reused. In the current research, the effect of oven-drying (50-70 °C) and freeze-drying on the bioactive compounds and antioxidant potential from Navelina, Salustriana, and Sanguina peel waste was investigated using pressurized extraction (ASE). Sixty volatile components were identified by ASE-GC-MS. The levels of terpene derivatives (sesquitenenes, alcohols, aldehydes, hydrocarbons, and esters) remained practically unaffected among fresh and freeze-dried orange peels, whereas drying at 70 °C caused significative decreases in Navelina, Salustriana, and Sanguina peels. Hesperidin and narirutin were the main flavonoids quantified by HPLC-MS. Freeze-dried Sanguina peels showed the highest levels of total-polyphenols (113.3 mg GAE·g-1), total flavonoids (39.0 mg QE·g-1), outstanding values of hesperedin (187.6 µg·g-1), phenol acids (16.54 mg·g-1 DW), and the greatest antioxidant values (DPPH•, FRAP, and ABTS•+ assays) in comparison with oven-dried samples and the other varieties. Nanotechnology approaches allowed the formulation of antioxidant-loaded nanoemulsions, stabilized with lecithin, starting from orange peel extracts. Those provided 70-80% of protection against oxidative UV-radiation, also decreasing the ROS levels into the Caco-2 cells. Overall, pressurized extracts from freeze-drying orange peel can be considered a good source of natural antioxidants that could be exploited in food applications for the development of new products of commercial interest.

Pressurized liquid extraction to obtain chia seeds oils extracts enriched in tocochromanols. Nanoemulsions approaches to preserve the antioxidant potential.

The objective of this study was to use accelerated-solvent-extraction to achieve antioxidant extracts from chia seeds oils, enriched in tocopherols and tocotrienols, namely tocochromanols. Nanotechnology applications have been also incorporated to develop an innovative formulation of chia seeds oil nanoemulsion that preserve its antioxidant potential after conditions of oxidative stress. Chia seeds oils proved to be a valuable source of tocochromanols, from 568.84 to 855.98 µg g-1, depending on the geographical provenance. Quantitative data obtained by LC-DAD-ESI-MS/MS showed outstanding levels of γ-Tocopherol, over 83%, followed far behind by Tocopherols-(α, ß, δ) and Tocotrienols-(α, ß, δ, γ)-tocotrienols. The characteristic tocochromanols fingerprint of chia seeds oils was positively correlated with the FRAP and DPPH antioxidant activity of the extracts (between 18.81 and 138.48 mg Trolox/g). Formulation of the Chia seeds oils as nanoemulsions did not compromised the antioxidant properties of fresh extracts. Interestingly, nanoemulsions retained about the 80% of the initial antioxidant capacity after UV-induced stress, where the non-emulsified oils displayed a remarkable reduction (50-60%) on its antioxidant capacity under the same conditions. These antioxidant chia seeds formulations can constitute a promising strategy to vectorizing vitamin E isomers, in order to be used for food fortification, natural additives and to increase the self-life of food products during packing.

Impact of previous admission to an intensive care unit on stem cell transplantation outcome.

INTRODUCTION: The impact of an admission to ICU before stem cell transplantation (SCT) on post-SCT outcome is not well established. PATIENTS AND METHODS: We reviewed the medical records of patients who had received a first SCT between 2000 and 2016 in our institution. The outcome of 22 patients who required ICU admission during chemotherapy prior to SCT (ICU group) was compared with 44 matched patients (1:2) who did not need it (NO-ICU group). RESULTS: There were no differences in transplant complications, in time to neutrophil and platelet recovery or in the length of hospital stay during SCT between the ICU and NO-ICU groups. However, microbiologically documented infections were more common in the ICU group (16/20) than in the NO-ICU group (18/39) (p=.027). The 5-yr overall survival probability (CI 95%) was 49% (28-70%) in the ICU vs. 45% (29-61%) in the NO-ICU group (p=.353), while the 5-yr incidence of non-relapse mortality was 32% (14-52%) and 24% (12-38%) (p=.333), respectively. Six patients (27%) in the ICU group and 8 (18%) in the NO-ICU group required admission to the ICU during or after the SCT procedure (p=.293). Twelve (54%) patients in the ICU and 22 (50%) in the NO-ICU group died, the causes of death were similar in both groups. CONCLUSION: Our results show that admission to the ICU prior to SCT does not have a negative impact on patient outcomes following SCT and should not be considered as an exclusion criterion for SCT.

eIF1A residues implicated in cancer stabilize translation preinitiation complexes and favor suboptimal initiation sites in yeast.

The translation pre-initiation complex (PIC) scans the mRNA for an AUG codon in favorable context, and AUG recognition stabilizes a closed PIC conformation. The unstructured N-terminal tail (NTT) of yeast eIF1A deploys five basic residues to contact tRNAi, mRNA, or 18S rRNA exclusively in the closed state. Interestingly, EIF1AX mutations altering the human eIF1A NTT are associated with uveal melanoma (UM). We found that substituting all five basic residues, and seven UM-associated substitutions, in yeast eIF1A suppresses initiation at near-cognate UUG codons and AUGs in poor context. Ribosome profiling of NTT substitution R13P reveals heightened discrimination against unfavorable AUG context genome-wide. Both R13P and K16D substitutions destabilize the closed complex at UUG codons in reconstituted PICs. Thus, electrostatic interactions involving the eIF1A NTT stabilize the closed conformation and promote utilization of suboptimal start codons. We predict UM-associated mutations alter human gene expression by increasing discrimination against poor initiation sites.

E1a is an exogenous in vivo tumour suppressor.

The E1a gene from adenovirus has become a major tool in cancer research. Since the discovery of E1a, it has been proposed to be an oncogene, becoming a key element in the model of cooperation between oncogenes. However, E1a's in vivo behaviour is consistent with a tumour suppressor gene, due to the block/delay observed in different xenograft models. To clarify this interesting controversy, we have evaluated the effect of the E1a 13s isoform from adenovirus 5 in vivo. Initially, a conventional xenograft approach was performed using previously unreported HCT116 and B16-F10 cells, showing a clear anti-tumour effect regardless of the mouse's immunological background (immunosuppressed/immunocompetent). Next, we engineered a transgenic mouse model in which inducible E1a 13s expression was under the control of cytokeratin 5 to avoid side effects during embryonic development. Our results show that E1a is able to block chemical skin carcinogenesis, showing an anti-tumour effect. The present report demonstrates the in vivo anti-tumour effect of E1a, showing that the in vitro oncogenic role of E1a cannot be extrapolated in vivo, supporting its future use in gene therapy approaches.

Survival of hematological patients after discharge from the intensive care unit: a prospective observational study.

INTRODUCTION: Although the survival rates of hematological patients admitted to the ICU are improving, little is known about the long-term outcome. Our objective was to identify factors related to long-term outcome in hematological patients after ICU discharge. METHODS: A prospective, observational study was carried out in seven centers in Spain. From an initial sample of 161 hematological patients admitted to one of the participating ICUs during the study period, 62 were discharged alive and followed for a median time of 23 (1 to 54) months. Univariate and multivariate analysis were performed to identify the factors related to long term-survival. Finally, variables that influence the continuation of the scheduled therapy for the hematological disease were studied. RESULTS: Mortality after ICU discharge was 61%, with a median survival of 18 (1 to 54) months. In the multivariate analysis, an Eastern Cooperative Oncology Group score (ECOG) >2 at ICU discharge (Hazard ratio 11.15 (4.626 to 26.872)), relapse of the hematological disease (Hazard ratio 9.738 (3.804 to 24.93)) and discontinuation of the planned treatment for the hematological disease (Hazard ratio 4.349 (1.286 to 14.705)) were independently related to mortality. Absence of stem cell transplantation, high ECOG and high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores decreased the probability of receiving the planned therapy for the hematological malignancy. CONCLUSIONS: Both ICU care and post-ICU management determine the long-term outcome of hematological patients who are discharged alive from the ICU.

Lack of impact of human immunodeficiency virus infection on the outcome of lymphoma patients transferred to the intensive care unit.

The impact of human immunodeficiency virus (HIV) infection on the outcome of patients with acquired immunodeficiency syndrome (AIDS)-related lymphoma with life-threatening complications requiring intensive care unit (ICU) admission is not well known. The objective of this study was to compare the outcome of patients with lymphoma transferred to the ICU according to HIV infection status. The clinical characteristics, reason for ICU admission, and outcome of 48 consecutive critically ill patients with lymphoma admitted to the ICU from January 2000 to March 2010 was retrospectively analyzed, focusing on their HIV serology status. Thirty-six patients were HIV-negative and 12 patients HIV-positive. Burkitt lymphoma was more frequent in HIV-infected patients, whereas diffuse large B-cell lymphoma was more frequent in HIV-negative patients. The main acute life-threatening diseases precipitating ICU transfer were similar in both groups. Severe neutropenia was more frequent in HIV-positive than in HIV-negative patients. With a median follow-up of 53 months after ICU admission, the overall survival probabilities were 15% (95% confidence interval [CI]: 3-27%) and 17% (95% CI: 0-38%) for HIV-negative and HIV-positive patients, respectively. The 2-year survival probabilities were 34% (95% CI: 10-58%) and 40% (95% CI: 0-43%) for HIV-negative and HIV-positive patients discharged from the ICU, respectively. In this study, HIV infection did not have a negative impact on the outcome of patients with lymphoma admitted to the ICU.

[Relationship between procalcitonin serum levels and complications and outcome of patients with hematological malignancy admitted to Intensive Care Unit]. / Relación entre los valores séricos de procalcitonina y las complicaciones y supervivencia de pacientes con hemopatías malignas ingresados en una Unidad de Vigilancia Intensiva.

BACKGROUND AND OBJECTIVE: Patients with hematological neoplasms transferred to an Intensive Care Unit (ICU) for a life-threatening complication have a poor outcome. In these patients, it is crucial to identify clinical and biologic parameters with potential prognostic significance. This study prospectively evaluated the usefulness of serum procalcitonin (PCT) levels as a predictor of complications (infectious or not) and outcome in these patients. PATIENTS AND METHOD: One hundred patients with hematological malignancy were admitted to the ICU from October 2004 until August 2009. In 59 of them serum PCT levels were daily measured from the ICU admission until a maximum period of 10 consecutive days. RESULTS: Hematological diseases were acute leukemia (n=30), lymphoma and other lymphoproliferative disorders (n=18), multiple myeloma (n=7) and other (n=4). Twenty-five patients (42%) had received hematopoietic stem cell transplantation. Thirty-seven patients (63%) presented neutropenia. Those patients who could not be discharged alive from the ICU presented higher PCT levels on days 1, 2 and 3. PCT levels were significantly higher in those patients with neutropenia or septic shock or other causes of hemodynamic instability. The presence of a microbiologically documented infection, respiratory failure or the need of mechanical ventilation support did not significantly affect PCT levels in this study. CONCLUSIONS: Early serum PCT levels measurement might be useful for predicting mortality in patients with hematological malignancy requiring advanced life support.

[Similar prognosis for transplanted and non-transplanted patients with hematological malignancy admitted to the intensive care unit]. / Similar supervivencia de los pacientes con neoplasia hematológica trasplantados y no trasplantados que requieren ingreso en una unidad de vigilancia intensiva.

BACKGROUND AND OBJECTIVE: There is scarce information on the influence of stem cell transplantation (SCT) on the prognosis of patients with hematological malignancies admitted to an intensive care unit (ICU). PATIENTS AND METHOD: The mortality during ICU admission, long-term survival and the prognostic factors for survival were analyzed and compared in transplanted vs. non-transplanted patients. RESULTS: 116 critically-ill patients with a hematological malignancy transferred to the ICU in a single institution were analyzed. Thirty patients had received SCT prior to ICU admission. Transplanted and non-transplanted patients were comparable for demographic variables (except age and disease status) and reasons for ICU admission. No differences were found in overall survival or survival after discharge from ICU between transplanted and non-transplanted patients. Thirty-nine out of 85 non-transplanted patients (46%) and 11 out of 31 transplanted patients (35%) could be discharged from the ICU. The prognostic factors for survival in non-transplanted patients were need of mechanical ventilation or cardiovascular vasoactive drugs. However, only the liver function impairment predicted the outcome in the transplanted patients through the multivariate analysis. CONCLUSIONS: A significant proportion of patients admitted to ICU were discharged despite previous SCT. These patients did not have a worse prognosis than those transferred to the ICU with a hematologic malignancy, although the prognostic factors for survival were different in the 2 groups of patients.

[Neutropenic enterocolitis in adult patients with acute leukemia or stem cell transplant recipients: study of 7 cases]. / Enterocolitis neutropénica en adultos con leucemia aguda o receptores de un trasplante de progenitores hematopoyéticos: estudio de 7 casos.

BACKGROUND AND OBJECTIVE: Neutropenic enterocolitis (NE) is a complication arising in neutropenic patients with acute leukemia or solid tumours while treated with intensive chemotherapy. The optimal therapeutic procedures have not been well established. PATIENTS AND METHOD: Seven cases of NE diagnosed and treated in a tertiary hospital between 2000 and 2007 are described. Their clinico-biological characteristics, therapeutic procedures and evolution were analysed retrospectively. RESULTS: Five of the patients were males, their median age was 39 years. Acute myeloblastic leukemia was the most frequent diagnosis (5 cases). Two other patients had received an stem cell transplantation. Abdominal pain was present in all patients, diarrhoea in 6, and fever in 5. Microorganisms were isolated from blood cultures in 4 cases (Clostridium septicum, Escherichia coli, Pseudomonas aeruginosa and Aeromonas hydrophila). Abnormal mural thickening of the caecum was observed in the 6 cases in which a computed tomography scan could be performed. The median mural thickness at its maximum section was 11 mm (range: 8-16). All patients first received medical treatment with wide spectrum antibiotics and intestinal rest, and abdominal surgery was indicated in 6 cases after a median time from first symptom of 4 days (range: 0-12). NE was confirmed histologically in all 6 patients. Five patients required admission in Intensive Care Unit and 2 (29%) died as a result of NE. CONCLUSIONS: NE is a severe complication of patients with hematologic malignancies submitted to intensive chemotherapy or receiving stem cell transplantation. Abdominal computed tomography scan is the most valuable diagnostic tool. Prompt surgical intervention may improve the prognosis in patients with NE.

Outcome and prognostic factors in patients with hematologic malignancies admitted to the intensive care unit: a single-center experience.

Patients who are admitted to the intensive care unit (ICU) with hematologic malignancies have a poor prognosis, although outcomes have improved in recent years. This study analyzed ICU mortality, short- and long-term survival, and prognostic factors for 100 consecutive critically ill patients with a hematologic malignancy who were admitted to our polyvalent ICU from January 2000 to May 2006. The median age was 55 years (range, 15-75 years; male-female ratio, 60:40). The main acute life-threatening diseases precipitating ICU transfer were respiratory failure (45 patients, 45%) and septic shock (33 patients, 33%). Forty-two patients (42%) were discharged from the ICU. The ICU mortality rate from 2004 to 2006 was lower than from 2000 to 2003 (49% versus 69%, P < .047). The 1- and 2-year probabilities of survival for patients discharged from the ICU were 67% (95% confidence interval [CI], 51%-84%) and 54% (95% CI, 34%-73%), respectively. A multivariate analysis revealed hemodynamic instability (odds ratio, 2.11; 95% CI, 1.17-3.83; P = .014) and mechanical ventilation (odds ratio, 4.27; 95% CI, 1.70-10.74; P = .002) to be the main predictors of a poor survival prognosis. Almost half of patients with hematologic malignancy and life-threatening complications can be discharged from the ICU. Age and underlying disease characteristics do not influence ICU outcome, which is mainly determined by hemodynamic and ventilatory status.

Intraoperative presacral electron boost following preoperative chemoradiation in T3-4Nx rectal cancer: initial local effects and clinical outcome analysis.

BACKGROUND AND PURPOSE: To analyze early results of a single institution experience using adjuvant intraoperative electron radiation therapy (IOERT) presacral boost in locally advanced rectal cancer following preoperative chemoradiation. MATERIALS AND METHODS: In a 63 month period (March 1995-June 2000), 100 consecutive T(3-4)N(x) rectal cancer patients were treated with preoperative chemoradiation (45-50 Gy plus oral Tegafur or 5-Fluorouracil continuous intravenous infusion), radical surgery and IOERT presacral boost (mean dose, 12.5 Gy; range, 10-15 Gy). Adjuvant chemotherapy (5-FU-leucovorin: 4-6 cycles) was given to 52 patients. The median age was 63 years, and 39 patients were >or=70 years old (65 males). Clinical staging was performed with computed tomography (94%) and/or endorectal ultrasound (71%) categorizing 90 cT(3), 10 cT(4), 20 cN(x), and 36 cN(+). Abdomino-perineal resection was performed in 41 cases. RESULTS: The IOERT cancellation rate was 6%. With a median follow-up of 23 months in IOERT treated patients, three developed pelvic recurrence: one anastomotic and one in the posterior vaginal wall (simultaneously with distant metastatic disease); and one presacral (in-field IOERT) as the only site of initial failure. Distant metastasis has been observed in 14 patients (exceptionally in pT(0-1) downstaged patients: 1/20; 5%). Overall treatment tolerances, including neoadjuvant and surgical segments, were acceptable. The actuarial 4-year estimations of local control, disease-free and overall survival are 94, 75 and 65%, respectively. CONCLUSIONS: IOERT electron boost to the presacral region is feasible to integrate systematically in the intensive combined treatment of locally advanced rectal cancer, including neoadjuvant chemoradiation segment. Topography of pelvic recurrences identified 2/3 relapses located in non-IOERT boosted anatomic intrapelvic sites: posterior vaginal wall and anastomotic suture. Presacral recurrence in locally advanced rectal cancer seems to be of low incidence, in a non-subspecialized academic surgical practice coordinated with a multidisciplinary oncology evaluation context, if an IOERT boost is included as a component of treatment together with preoperative chemoradiation.