Melatonin modulates the cadmium-induced expression of MT-2 and MT-1 metallothioneins in three lines of human tumor cells (MCF-7, MDA-MB-231 and HeLa)

Cadmium (Cd) is a human carcinogen present in tobacco smoke and contaminated industrial soils. Metallothioneins (MTs) are intracellular proteins involved in protecting against Cd. The toxic effects of Cd can be modified by compounds able to modulate MTs synthesis. Melatonin has oncostatic properties and has also been shown to counteract the toxic effects of Cd. In this study we examine the possible role of melatonin in Cd-induced expression of several MT isoforms (MT-2A, MT-1X, MT-1F and MT-1E) in three human tumor cell lines (MCF-7, MDA-MB-231 and HeLa). We found that, in all cell types, melatonin increases Cd-induced expression of MT-2A, which is considered to protect against Cd toxicity. As regards MT-1 subtypes, which have been related with cell invasiveness and high histological grade tumors, melatonin caused Cd-induced expression in both breast cancer cell lines to decrease. These effects point towards melatonin's possible role as a preventive agent for carcinogenesis dependent on Cd contamination.     

Methodological issues associated with clinical trials in epilepsy

Introduction: despite methodological advances in epilepsy clinical trials, the proportion of patients reaching seizure-freedom has not substantially changed over the years. We review the main methodological limitations of current trials, the possible strategies to overcome these limits, and the issues that need to be addressed in next future.

Area covered: references were identified by PubMed search until March 2017 and unpublished literature was searched on ClinicalTrials.gov. Add-on trials mainly involve refractory epilepsy subjects, reducing overall response to the investigational drug. The inclusion of subjects with earlier disease from less developed countries has partially allowed overcoming this limitation, but has introduced more random variability of results. Monotherapy trials rise methodological, economical, and ethical concerns with different regulatory requirements in European Union and in the United States of America. Newer trial designs, such as futility trials or ‘time-to-event’ design, have been implemented. Moreover, both add-on and monotherapy trials results might be affected by patient’s ability to recognize and record seizures, and by randomness of seizures occurrence over time. Possible strategies to achieve more reliable outcomes are detailed.

Expert commentary: clinical trial methodology needs to be optimized to better address regulatory agencies requirements and to encounter both patients’ and clinicians’ needs.     

Assessment of the Relative Catch Performance of a Surrounding Net without the Purse Line as an Alternative to a Traditional Boat Seine in Small-Scale Fisheries

The catch performance of a traditional Ligurian boat seine, which is not in line with the European Union regulation, was compared with an experimental surrounding net without the purse line as a potential legal alternative. The relative catch performance between the two gear types was assessed using a new catch comparison method requiring neither paired data collection nor equal number of hauls with the two gears. The comparison was based on the catches of the three species that comprise the bulk of the catch in traditional Ligurian boat seine fisheries: Bogue Boops boops, Saddle Bream Oblada melanura, and Blotched Picarel Spicara maena. The experimental gear exhibited poor catch efficiency for all three species, since it was estimated that the catches would only be 2, 64, and 6%, respectively, of those with the boat seine. For both Bogue and Blotched Picarel these reductions in catch performance were found to be highly significant proving that the experimental surrounding net is not a viable solution to replace the traditional boat seine.

Received February 4, 2015; accepted September 15, 2015     

Busulfan- or Thiotepa-Based Conditioning in Myelofibrosis: A Phase II Multicenter Randomized Study from the GITMO Group

We report a randomized study comparing fludarabine in combination with busulfan (FB) or thiotepa (FT), as conditioning regimen for hematopoietic stem cell transplantation (HSCT) in patients with myelofibrosis. The primary study endpoint was progression-free survival (PFS).Sixty patients were enrolled with a median age of 56 years and an intermediate-2 or high-risk score in 65%, according to the Dynamic International Prognostic Staging System (DIPSS). Donors were HLA-identical sibling (n = 25), matched unrelated (n = 25) or single allele mismatched unrelated (n = 10). With a median follow-up of 22 months (range, 1 to 68 months), outcomes at 2 years after HSCT in the FB arm versus the FT arm were as follows: PFS, 43% versus 55% (P = .28); overall survival (OS), 54% versus 70% (P = .17); relapse/progression, 36% versus 24% (P = .24); nonrelapse mortality (NRM), 21% in both arms (P = .99); and graft failure, 14% versus 10% (P = .96). A better PFS was observed in patients with intermediate-1 DIPSS score (P = .03). Both neutrophil engraftment and platelet engraftment were significantly influenced by previous splenectomy (hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.16 to 4.51; P = .02) and splenomegaly at transplantation (HR, 0.51; 95% CI, 0.27 to 0.94; P = .03). In conclusion, the clinical outcome after HSCT was comparable when using either a busulfan or thiotepa based conditioning regimen.     

Learning styles and gross anatomy assessment outcomes at a Colombian School of Medicine

The term, “learning styles” refers to the concept that individuals have as regards the method of instruction or study that is most efficient for them. It has been proposed that optimal learning occurs when the preferences of the primary learning style of the student correspond to the course content and the method of instruction. The Visual, Aural, Written/Read and Kinesthetic (VARK) model is a preferred instruction model. The objective of the study was to investigate the relationship between the VARK preferences and the Gross Anatomy test results of a group of students from the Universidad del Norte. The study included 111 (61 female and 50 male) students enrolled in their third semester of medical school in the skeletomuscular system during the summer of 2015. The VARK Aural and Kinesthetic modes were the most common (34.2% and 26.1%, respectively), while Visual was the learning style with the lowest number of representatives (9%). The multimodal style was preferred by 12.6% of the students involved. There was no significant statistical relationship (X² = 2.61; p = .62 and X² = 5.4; p = .24) between the VARK modes and the mid-term test results. The Aural and Kinesthetic modes showed significant negative correlations with the mid-term electronic multiple-choice assessment (r_s = ?0.19; p = .03; and (r_s = ?0.24; p = .01). Although different teaching strategies were offered to the students, no significant differences were observed. However, the students with Aural and Kinesthetic modes did show a negative correlation with the mid-term electronic multiple-choice assessment.