Treatment allocation in patients with hepatocellular carcinoma: Need for a paradigm shift?

Letter

Optimization of frying process in food safety

The mechanics of frying are fairly simple. Hot oil serves as a heat exchange medium in which heat is transferred to the food being fried. As a result, the heat converts water within the food to steam and melts the fat within the food. The steam and fat then migrate from the interior of the food through the exterior and into the oil. Conversely, some of the frying oil is absorbed into the food being fried. The chemistry occurring in the frying oil and in the food being fried includes a myriad of thermal and oxidative reactions involving lipids, proteins, carbohydrates and minor food constituents. Decomposition products by autoxidation above 100°C, polimerization without oxigen between 200-300°C and thermal oxidation at 200°C, can be produced in frying oil and their amounts are related to different chemical and physical parameters such as temperature, heating time, type of oil used and food being fried, oil turnover rate, management of the oil and finally type of equipment used. Different studies have remarked as the toxicity of these by-products, is due to their chemistry and concentration. Since the prime requirement in food quality is the safety of the products, attainable through preventive analysis of the risks and total control through all frying processes, in this work the critical points of particular importance are identify and showed: Oil composition, and in particular its antioxidant capacity. Proper fryer design. Food/oil ratio. Good manufactured practice. Beside the quality screening has to be direct towards the chemical quality evaluation by easy and rapid analysis of oil (colour, polar compounds, free fatty acids and antioxidant capacity) and food fried (panel test and/or consumer test). Conclusion, to maintain high quality in the frying medium, choose efficient equipment, select a fat with desirable flavour and good antioxidant capacity, eliminate crackling as soon and often as possible, choose better components with minimal but desirable browning tendencies, and monitor the quality of the fat being used

Child Neurology: A Case Series of Heterogeneous Neuropsychiatric Symptoms and Outcome in Very Early-Onset Narcolepsy Type 1

Narcolepsy type 1 is a central disorder of hypersomnolence characterized by excessive daytime sleepiness, cataplexy (i.e., sudden loss of muscle tone during wakefulness triggered by emotions), and REM sleep-related manifestations that can present with a peculiar phenotype when arising at a pediatric age. Several features of childhood-onset narcolepsy type 1 are also common in neuropsychiatric conditions; discrete neuropsychiatric comorbidity has also been demonstrated. Here, we report on 3 children with very early narcolepsy type 1. All 3 patients had psychiatric features at the time of symptom onset coupled with peculiar motor disturbances. The course of narcolepsy symptoms also paralleled neuropsychiatric symptoms, suggesting a possible intrinsic link between sleep and psychological features. Multidisciplinary management is mandatory for pediatric narcolepsy type 1 since prompt disease management addressing neuropsychiatric symptoms could lead to better clinical outcomes and quality of life

Efficient Delivery of MicroRNA and AntimiRNA Molecules Using an Argininocalix[4]arene Macrocycle

MicroRNAs (miRNAs) are short non-coding RNA molecules acting as gene regulators by repressing translation or by inducing degradation of the target RNA transcripts. Altered expression of miRNAs may be involved in the pathogenesis of many severe human diseases, opening new avenues in the field of therapeutic strategies, i.e., miRNA targeting or miRNA mimicking. In this context, the efficient and non-toxic delivery of premiRNA and antimiRNA molecules might be of great interest. The aim of the present paper is to determine whether an argininocalix[4]arene is able to efficiently deliver miRNA, premiRNA, and antimiRNA molecules to target cells, preserving their biological activity. This study points out that (1) the toxicity of argininocalix[4]arene 1 is low, and it can be proposed for long-term treatment of target cells, being that this feature is a pre-requisite for the development of therapeutic protocols; (2) the delivery of premiRNA and antimiRNA molecules is efficient, being higher when compared with reference gold standards available; and (3) the biological activity of the premiRNAs and antimiRNAs is maintained. This was demonstrated using the argininocalix[4]arene 1 in miRNA therapeutic approaches performed on three well-described experimental model systems: (1) the induction of apoptosis by antimiR-221 in glioma U251 cells; (2) the induction of apoptosis by premiR-124 in U251 cells; and (3) the inhibition of pro-inflammatory IL-8 and IL-6 genes in cystic fibrosis IB3-1 cells. Our results demonstrate that the argininocalix[4]arene 1 should be considered a very useful delivery system for efficient transfer to target cells of both premiRNA and antimiRNA molecules, preserving their biological activity

An active feedback recovery technique from disruption events induced by m=2 n=1 tearing modes in ohmically heated tokamak plasmas

We present experimental results of magnetic feedback control on the m=2, n=1 tearing mode in RFX-mod operated as a circular ohmically heated tokamak. The feedback suppression of the non-resonant m=2, n=1 Resistive Wall Mode (RWM) in q(a)<2 plasmas is a well-established result of RFX-mod. The control of the tearing counterpart, which develops in q(a)>2 equilibrium, is instead a more difficult issue. In fact, the disruption induced by a growing amplitude m=2, n=1 tearing mode can be prevented by feedback only when the resonant surface q=2 is close to the plasma edge, namely 2<q(a)<2.5, and the electron density does not exceed approximately half of the Greenwald limit. A combined technique of tearing mode and q(a) control has been therefore developed to recover the discharge from the most critical conditions: the potentially disruptive tearing mode is converted into the relatively benign RWM by suddenly decreasing q(a) below 2. The experiments demonstrate the concept with 100% of successful cases. The q(a) control has been performed through the plasma current, given the capability of the toroidal loop-voltage power supply of RFX-mod. We also propose a path for controlling q(a) by acting on the plasma shape, which could be applied to medium size elongated tokamaks

Emergency Surgery in the Elderly: Could Laparoscopy Be Useful in Frailty? A Single-Center Prospective 2-Year Follow-Up in 120 Consecutive Patients

Background: the general population is aging across the world. Therefore, even surgical interventions in the elderly—in particular those involving emergency surgical admissions—are becoming more frequent. The elderly population is often frail (in multiple physiological systems, this is often defined as age-related cumulative decline). This study involved a 2-year follow-up evaluation of frail elderly patients treated with urgent surgical intervention at Santa Maria Regina della Misericordia Hospital, General Surgery Department, in Adria (Italy). Method: a prospective, single-center, 2-year follow-up study of 120 patients &gt;65 years old, treated at our department for surgical abdominal emergencies. We considered co-morbidities (ASA—American Society of Anesthesiologists Physical Status Classification System—score), type of surgery (laparoscopy, laparotomy or converted), frailty score, mortality, and complications at 30 days and at 2 years. Conclusions: 70 (58.4%) patients had laparoscopy, 49 (40.8) had laparotomy, and in 1 (0.8%) case, surgery was converted from laparoscopy to laparotomy. Mortality strictly depends on the type of surgery (laparotomy vs. laparoscopy), complications during recovery, and a lower Fried frailty criteria score, on average. The long-term follow-up can be a useful tool to highlight a safer surgical approach, such as laparoscopy, in frail elderly patients. We consider the laparoscopic approach feasible in emergency situations, with similar or better outcomes than laparotomy, especially in frail elderly patients

The role of antiplatelet therapies on incidence and mortality of hepatocellular carcinoma

Aim To evaluate the impact of antiplatelet therapy (APT)on the incidence of hepatocellular carcinoma (HCC) and mortality following its treatment. Methods A systematic literature search was performed using PubMed and Cochrane Central Register of Controlled Trials Databases. Two HCC clinical settings were explored: (i) incidence, and (ii) death after any HCC treatment. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the pooled data between patients who received or did not receive APT. Results A total of 20 studies were identified, of whom 15 focused on HCC incidence, including 2,685,009 patients, and five on post-treatment death, including 3281 patients. APT was associated with an overall reduced risk of HCC incidence (OR: 0.63; 95%CI = 0.51-0.79; p &lt; 0.001) as well as of post-treatment mortality (OR: 0.54; 95%CI = 0.35-0.83; p = 0.006). Conclusions Current data suggest that APT correlated with higher HCC incidence and poor overall survival following tumour treatment

A peptide-nucleic acid targeting miR-335-5p enhances expression of cystic fibrosis transmembrane conductance regulator (CFTR) gene with the possible involvement of the CFTR scaffolding protein NHERF1

(1) Background: Up-regulation of the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) might be of great relevance for the development of therapeutic protocols for cystic fibrosis (CF). MicroRNAs are deeply involved in the regulation of CFTR and scaffolding proteins (such as NHERF1, NHERF2 and Ezrin). (2) Methods: Content of miRNAs and mRNAs was analyzed by RT-qPCR, while the CFTR and NHERF1 production was analyzed by Western blotting. (3) Results: The results here described show that the CFTR scaffolding protein NHERF1 can be upregulated in bronchial epithelial Calu-3 cells by a peptide-nucleic acid (PNA) targeting miR-335-5p, predicted to bind to the 3′-UTR sequence of the NHERF1 mRNA. Treatment of Calu-3 cells with this PNA (R8-PNA-a335) causes also up-regulation of CFTR. (4) Conclusions: We propose miR-335-5p targeting as a strategy to increase CFTR. While the efficiency of PNA-based targeting of miR-3355p should be verified as a therapeutic strategy in CF caused by stop-codon mutation of the CFTR gene, this approach might give appreciable results in CF cells carrying other mutations impairing the processing or stability of CFTR protein, supporting its application in personalized therapy for precision medicine

Enzymatic spermine metabolites induce apoptosis associated with increase of p53, caspase-3 and mir-34a in both neuroblastoma cells, SJNKP and the N-Myc-amplified form IMR5

Neuroblastoma (NB) is a common malignant solid tumor in children and accounts for 15% of childhood cancer mortality. Amplification of the N-Myc oncogene is a well-established poor prognostic marker in NB patients and strongly correlates with higher tumor aggression and resistance to treatment. New therapies for patients with N-Myc-amplified NB need to be developed. After treating NB cells with BSAO/SPM, the detection of apoptosis was determined after annexin V-FITC labeling and DNA staining with propidium iodide. The mitochondrial membrane potential activity was checked, labeling cells with the probe JC-1 dye. We analyzed, by real-time RT-PCR, the transcript of genes involved in the apoptotic process, to determine possible down-or upregulation of mRNAs after the treatment on SJNKP and the N-Myc-amplified IMR5 cell lines with BSAO/SPM. The experiments were carried out considering the proapoptotic genes Tp53 and caspase-3. After treatment with BSAO/SPM, both cell lines displayed increased mRNA levels for all these proapoptotic genes. Western blotting analysis with PARP and caspase-3 antibody support that BSAO/SPM treatment induces high levels of apoptosis in cells. The major conclusion is that BSAO/SPM treatment leads to antiproliferative and cytotoxic activity of both NB cell lines, associated with activation of apoptosis