Ethical Approach to Prevention of Schizophrenia - Concepts and Challenges.

Patients with schizophrenia, nowadays chronic, frequently disabling mental disorder, get initial treatment after detection of a psychotic episode, seemingly late, potentially preventable stage of illness. As our knowledge about the nature of schizophrenia and other diseases of the spectrum is growing, so are the early interventions becoming more possible, and it is important to conceptualize the clinical, legal and moral issues emerging with new preventive treatments. Every intervention, especially in pre-clinical population, demands a careful risk-benefit assessment and having basic bioethical principles - primacy of patient's welfare, beneficience/non-maleficience, autonomy and justice - in mind. We believe that pharmacological treatments, considering today's drugs safety and effectiveness profiles, should stay reserved for cases with higly probable negative outcomes to patient's wellbeing, and that all other low-risk interventions, like psychosocial treatments, should be considered for reducing the conversion to disorder, if possible, or relieving the distress in vulnerable persons, when such vulnerability gets detected. How to recognize persons at risk before the start of the disorder, without missing the majority of cases or burdening healthy persons with stigma, is another challenge and not only mental health professionals should be included in finding the solutions. The broadest public, and especially the experts that will build the safety-net for the at-risk individuals, should get best possible appropriate education about the schizophrenia in order to stigmatize less and help more.

Ethical Overview of Placebo Control in Psychiatric Research - Concepts and Challenges.

Permissibility of placebo controls in psychiatric research is raising everlasting controversies. The main ethical issue remains: whether, when, under what conditions, and to what extent is it justifiable to disregard subject's present (best) interest for the presumably "greater" ones. In relation to this main ethical concern, two distinct arguments arose: proponents of placebo controls trials (placebo ortxodoxy) and proponents of active controls trials (active-control orthodoxy). More recently, in new ethical guidelines, Declaration of Helsinki and International Ethical Guidelines for Biomedical Research Involving Human Subjects, a "middle way" approach was formulated, acceptable to both sides of the argument, saying placebo controls can be justified under certain conditions: when and only when, they firstly present undisputed methodological reasoning, and secondly, fulfill certain ethical considerations - mainly regarding the permissibility of accompanied risks. These ethical evaluations are inevitably contextual and evoke the need for the principle of proportionality. In scope of recent findings of substantial and progressively increasing placebo response in psychiatric research, contextual factors are identified and both theoretical and practical challenges are discussed.

Informed consent in psychiatric research - concepts and challenges.

Research involving vulnerable population of mentally impaired persons is raising considerable controversies from its very beginnings. These controversies are created around everlasting tensions between two positive duties: the duty to protect vulnerable subjects, and the duty not to deny them potential benefits. Most of the contemporary ethical guidelines and regulations, including most recent revision of the Declaration of Helsinki, permit these researches under certain ethical conditions. The notion of informed consent as a cornerstone of bioethics emerges as essential requisite of moral research. We are presenting some key concepts and safeguards regarding informed consent that researcher needs to be aware off when conducting a research involving mentally impaired persons. Theoretical and practical challenges that are arising from these safeguards are discussed with an overview of most recent scientific data. Lastly, we briefly address the most important legal standings that will be introduced in 2015, by new Croatian Law on the Protection of Persons with Mental Disorders.

Replication error-positive samples found in pheochromocytomas.

UNLABELLED: Adenomatous polyposis coli, (APC) and E-cadherin (CDH1) tumor suppressor genes were investigated in human pheochromocytoma. Both genes are components of adherens junctions, but are also involved in wnt signalling in which one of the target molecules is c-myc protein. MATERIALS AND METHODS: Fifteen sporadic pheochromocytomas were tested for gene instability by PCR/loss of heterozygosity. Detection of c-myc protein was performed using immunohistochemistry. RESULTS: One sample with allelic imbalance of the APC gene and one with allelic imbalance of the CDH1 gene were found. Interestingly, another type of genomic instability was detected--replication error-positive samples (RER+). Four out of 13 heterozygous samples were RER-positive (30.8%). The instability is the result of impaired cellular mismatch repair. Immunohistochemistry showed increased levels of c-myc in comparison to normal adrenal tissue. CONCLUSION: Our results suggest that microsatellite genetic instabilities of the E-cadherin gene have a role in pheochromocytoma development and progression. Detected instability indicates that mismatch repair may be targeted in pheochromocytoma. Increased expression of c-myc protein as well as allelic imbalances of APC and CDH 1 genes suggest that the wnt signalling pathway may have a role in this malignancy.

Blending problem-based learning with Web technology positively impacts student learning outcomes in acid-base physiology.

World Wide Web (Web)-based learning (WBL), problem-based learning (PBL), and collaborative learning are at present the most powerful educational options in higher education. A blended (hybrid) course combines traditional face-to-face and WBL approaches in an educational environment that is nonspecific as to time and place. To provide educational services for an undergraduate second-year elective course in acid-base physiology, a rich, student-centered educational Web-environment designed to support PBL was created by using Web Course Tools courseware. The course is designed to require students to work in small collaborative groups using problem solving activities to develop topic understanding. The aim of the study was to identify the impact of the blended WBL-PBL-collaborative learning environment on student learning outcomes. Student test scores and satisfaction survey results from a blended WBL-PBL-based test group (n = 37) were compared with a control group whose instructional opportunities were from a traditional in-class PBL model (n = 84). WBL students scored significantly (t = 3.3952; P = 0.0009) better on the final acid-base physiology examination and expressed a positive attitude to the new learning environment in the satisfaction survey. Expressed in terms of a difference effect, the mean of the treated group (WBL) is at the 76th percentile of the untreated (face-to-face) group, which stands for a "medium" effect size. Thus student progress in the blended WBL-PBL collaborative environment was positively affected by the use of technology.

Genetic changes of the E-cadherin and APC tumour suppressor genes in clear cell renal cell carcinoma.

AIMS: The roles of tumour suppressor genes: adenomatous polyposis coli (APC) and E-cadherin (CDH1) were investigated in clear cell renal cell carcinoma. METHODS: Forty-five human clear cell renal cell carcinomas were tested for APC gene instability by polymerase chain reaction/loss of heterozygosity using the restriction fragment length polymorphism method. E-cadherin gene was analysed by PCR amplification of tetranucleotide marker (D16S752) and the alleles were visualised by PAGE/silver staining. RESULTS: The overall proportion of loss of heterozygosity of the APC gene was 37.5% (9/24). D16S752 marker linked to E-cadherin gene (informativeness 91%) revealed three samples with loss of heterozygosity (7.5%). Interestingly, replication error phenotype was detected in 9.1% of clear cell renal cell carcinoma samples. Multivariate statistical analysis of samples informative for both APC and E-cadherin genes showed that, in this data set, loss of heterozygosity of the APC gene is correlated with advanced age and more severe TNM stages. Genetic changes of the E-cadherin gene, on the other hand, appear to be correlated with younger age groups and less severe TNM stages. CONCLUSIONS: Our results suggest that alterations, both in APC and E-cadherin genes, are involved in the evolution and progression of clear cell renal cell carcinoma. Microsatellite genetic instability of the E-cadherin gene indicates that another cellular mechanism, mismatch repair, may also be targeted in this malignancy.