Erasmus Mundus Master of Bioethics: a case for an effective model for international bioethics education

Designing bioethics curriculum for international postgraduate students is a challenging task. There are at least two main questions, which have to be resolved in advance: (1) what is a purpose of a particular teaching program and (2) how to respectfully arrange a classroom for students coming from different cultural and professional backgrounds. In our paper we analyze the case of the Erasmus Mundus Master of Bioethics program and provide recommendations for international bioethics education. In our opinion teaching bioethics to postgraduate international students goes beyond curriculum. It means that such a program requires not only well-defined goals, including equipping students with necessary skills and knowledge, but also it should first and foremost facilitate positive group dynamics among students and enables them to engage in dialogue to learn from one another

A screen to identify drug resistant variants to target-directed anti-cancer agents

The discovery of oncogenes and signal transduction pathways important for mitogenesis has triggered the development of target-specific small molecule anti-cancer compounds. As exemplified by imatinib (Gleevec), a specific inhibitor of the Chronic Myeloid Leukemia (CML)-associated Bcr-Abl kinase, these agents promise impressive activity in clinical trials, with low levels of clinical toxicity. However, such therapy is susceptible to the emergence of drug resistance due to amino acid substitutions in the target protein. Defining the spectrum of such mutations is important for patient monitoring and the design of next-generation inhibitors. Using imatinib and BCR/ABL as a paradigm for a drug-target pair, we recently reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations. Here we provide a detailed methodology for the screen, which can be generally applied to any drug-target pair

Effect of tadalafil on blood flow, pain, and function in chronic cold Complex Regional Pain Syndrome: a randomized controlled trial

Background. This double-blind, randomized, controlled trial investigated the effect of the phosphodiesterase-5 inhibitor tadalafil on the microcirculation in patients with cold Complex Regional Pain Syndrome (CRPS) in one lower extremity. Methods. Twenty-four patients received 20 mg tadalafil or placebo daily for 12 weeks. The patients also participated in a physical therapy program. The primary outcome measure was temperature difference between the CRPS side and the contralateral side, determined by measuring the skin temperature with videothermography. Secondary outcomes were: pain measured on a Visual Analogue Scale, muscle force measured with a MicroFet 2 dynamometer, and level of activity measured with an Activity Monitor (AM) and walking tests. Results. At the end of the study period, the temperature asymmetry was not significantly reduced in the tadalafil group compared with the placebo group, but there was a significant and clinically relevant reduction of pain in the tadalafil group. Muscle force improved in both treatment groups and the AM revealed small, non-significant improvements in time spent standing, walking, and the number of short walking periods. Conclusion. Tadalafil may be a promising new treatment for patients that have chronic cold CRPS due to endothelial dysfunction, and deserves further investigation. Trial Registration. The registration number in the Dutch Trial Register is ISRCTN60226869

Peripheral killer cells do not differentiate between asthma patients with or without fixed airway obstruction

Objective: The three main types of killer cells – CD8+ T cells, NK cells and NKT cells – have been linked to asthma and chronic obstructive pulmonary disease (COPD). However, their role in a small subset of asthma patients displaying fixed airway obstruction (FAO), similar to that seen in COPD, has not been explored. The objective of the present study was to investigate killer cell numbers, phenotype and function in peripheral blood from asthma patients with FAO, asthma patients without FAO, and healthy individuals. Methods: Peripheral CD8+ T cells (CD8+CD3+CD56−), NK cells (CD56+CD3−) and NKT-like cells (CD56+CD3+) of 14 asthma patients with FAO (post-bronchodilator FEV/FVC <0.7, despite clinician-optimised treatment), 7 asthma patients without FAO (post-bronchodilator FEV/FVC ≥0.7), and 9 healthy individuals were studied. Results: No significant differences were seen between the number, receptor expression, MAPK signalling molecule expression, cytotoxic mediator expression, and functional cytotoxicity of peripheral killer cells from asthma patients with FAO, asthma patients without FAO and healthy individuals. Conclusions: Peripheral killer cell numbers or functions do not differentiate between asthma patients with or without fixed airway obstruction

The Rho family GEF FARP2 is activated by aPKC iota to control tight junction formation and polarity

The elaboration of polarity is central to organismal development and to the maintenance of functional epithelia. Among the controls determining polarity are the PAR proteins, PAR6, aPKCι and PAR3, regulating both known and unknown effectors. Here, we identify FARP2 as a ‘RIPR’ motif-dependent partner and substrate of aPKCι that is required for efficient polarisation and junction formation. Binding is conferred by a FERM/FA domain–kinase domain interaction and detachment promoted by aPKCι-dependent phosphorylation. FARP2 is shown to promote GTP loading of Cdc42, which is consistent with it being involved in upstream regulation of the polarising PAR6–aPKCι complex. However, we show that aPKCι acts to promote the localised activity of FARP2 through phosphorylation. We conclude that this aPKCι−FARP2 complex formation acts as a positive feedback control to drive polarisation through aPKCι and other Cdc42 effectors

Prevalence Rates of Mental Disorders in Chilean Prisons

PMCID: PMC371883

The epidemiology of injuries across the weight-training sports

Background: Weight-training sports, including weightlifting, powerlifting, bodybuilding, strongman, Highland Games, and CrossFit, are weight-training sports that have separate divisions for males and females of a variety of ages, competitive standards, and bodyweight classes. These sports may be considered dangerous because of the heavy loads commonly used in training and competition. Objectives: Our objective was to systematically review the injury epidemiology of these weight-training sports, and, where possible, gain some insight into whether this may be affected by age, sex, competitive standard, and bodyweight class. Methods: We performed an electronic search using PubMed, SPORTDiscus, CINAHL, and Embase for injury epidemiology studies involving competitive athletes in these weight-training sports. Eligible studies included peer-reviewed journal articles only, with no limit placed on date or language of publication. We assessed the risk of bias in all studies using an adaption of the musculoskeletal injury review method. Results: Only five of the 20 eligible studies had a risk of bias score ≥75 %, meaning the risk of bias in these five studies was considered low. While 14 of the studies had sample sizes >100 participants, only four studies utilized a prospective design. Bodybuilding had the lowest injury rates (0.12–0.7 injuries per lifter per year; 0.24–1 injury per 1000 h), with strongman (4.5–6.1 injuries per 1000 h) and Highland Games (7.5 injuries per 1000 h) reporting the highest rates. The shoulder, lower back, knee, elbow, and wrist/hand were generally the most commonly injured anatomical locations; strains, tendinitis, and sprains were the most common injury type. Very few significant differences in any of the injury outcomes were observed as a function of age, sex, competitive standard, or bodyweight class. Conclusion: While the majority of the research we reviewed utilized retrospective designs, the weight-training sports appear to have relatively low rates of injury compared with common team sports. Future weight-training sport injury epidemiology research needs to be improved, particularly in terms of the use of prospective designs, diagnosis of injury, and changes in risk exposure

Open tension free repair of inguinal hernias; the Lichtenstein technique

BACKGROUND: Recurrences have been a significant problem following hernia repair. Prosthetic materials have been increasingly used in hernia repair to prevent recurrences. Their use has been associated with several advantages, such as less postoperative pain, rapid recovery, low recurrence rates. METHODS: In this retrospective study, 540 tension-free inguinal hernia repairs were performed between August 1994 and December 1999 in 510 patients, using a polypropylene mesh (Lichtenstein technique). The main outcome measure was early and late morbidity and especially recurrence. RESULTS: Inguinal hernia was indirect in 55 % of cases (297 patients), direct in 30 % (162 patients) and of the pantaloon (mixed) type in 15 % (81 patients). Mean patient age was 53.7 years (range, 18 – 85). Follow-up was completed in 407 patients (80 %) by clinical examination or phone call. The median follow-up period was 3.8 years (range, 1 – 6 years). Seroma and hematoma formation requiring drainage was observed in 6 and 2 patients, respectively, while transient testicular swelling occurred in 5 patients. We have not observed acute infection or abscess formation related to the presence of the foreign body (mesh). In two patients, however, a delayed rejection of the mesh occurred 10 months and 4 years following surgery. There was one recurrence of the hernia (in one of these patients with late mesh rejection) (recurrence rate = 0.2 %). Postoperative neuralgia was observed in 5 patients (1 %). CONCLUSION: Lichtenstein tension-free mesh inguinal hernia repair is a simple, safe, comfortable, effective method, with extremely low early and late morbidity and remarkably low recurrence rate and therefore it is our preferred method for hernia repair since 1994

Melarsoprol cyclodextrin inclusion complexes as promising oral candidates for the treatment of human African trypanosomiasis

Human African trypanosomiasis (HAT), or sleeping sickness, results from infection with the protozoan parasites &lt;i&gt;Trypanosoma brucei&lt;/i&gt; (&lt;i&gt;T.b.&lt;/i&gt;) &lt;i&gt;gambiense&lt;/i&gt; or &lt;i&gt;T.b.rhodesiense&lt;/i&gt; and is invariably fatal if untreated. There are 60 million people at risk from the disease throughout sub-Saharan Africa. The infection progresses from the haemolymphatic stage where parasites invade the blood, lymphatics and peripheral organs, to the late encephalitic stage where they enter the central nervous system (CNS) to cause serious neurological disease. The trivalent arsenical drug melarsoprol (Arsobal) is the only currently available treatment for CNS-stage &lt;i&gt;T.b.rhodesiense&lt;/i&gt; infection. However, it must be administered intravenously due to the presence of propylene glycol solvent and is associated with numerous adverse reactions. A severe post-treatment reactive encephalopathy occurs in about 10% of treated patients, half of whom die. Thus melarsoprol kills 5% of all patients receiving it. Cyclodextrins have been used to improve the solubility and reduce the toxicity of a wide variety of drugs. We therefore investigated two melarsoprol cyclodextrin inclusion complexes; melarsoprol hydroxypropyl-&#846;-cyclodextrin and melarsoprol randomly-methylated-&#946;-cyclodextrin. We found that these compounds retain trypanocidal properties &lt;i&gt;in vitro&lt;/i&gt; and cure CNS-stage murine infections when delivered orally, once per day for 7-days, at a dosage of 0.05 mmol/kg. No overt signs of toxicity were detected. Parasite load within the brain was rapidly reduced following treatment onset and magnetic resonance imaging showed restoration of normal blood-brain barrier integrity on completion of chemotherapy. These findings strongly suggest that complexed melarsoprol could be employed as an oral treatment for CNS-stage HAT, delivering considerable improvements over current parenteral chemotherapy