Ethical aspects of human biobanks: a systematic review

Aim

To systematically assess the existing literature on ethical aspects of human biobanks.

Method

We searched the Web of Science and PubMed databases to find studies addressing ethical problems in biobanks with no limits set (study design, study population, time period, or language of publication). All identified articles published until November 2010 were included. We analyzed the type of published articles, journals publishing them, involvement of countries/institutions, year of publication, and citations received, and qualitatively assessed every article in order to identify ethical issues addressed by the majority of published research on human biobanking.

Results

Hundred and fifty four studies satisfied our review criteria. The studies mainly came from highly developed countries and were all published in the last two decades, with over half of them published in 2009 or 2010. They most commonly discussed the informed consent, privacy and identifiability, return of results to participants, importance of public trust, involvement of children, commercialization, the role of ethics boards, international data exchange, ownership of samples, and benefit sharing.

Conclusions

The focus on ethical aspects is strongly present through the whole biobanking research field. Although there is a consensus on the old and most typical ethical issues, with further development of the field and increasingly complex structure of human biobanks, these issues will likely continue to arise and accumulate, hence requiring constant re-appraisal and continuing discussion.Biobanks comprise organized collections of human biological samples, usually associated personal health information, which are used together for biomedical research. Research results are generally very important for the society and biobanks have been heavily supported by many governments. Thus, in the recent few years biobanks have undergone rapid proliferation and have become increasingly complex. Their complexity has arisen from an increasingly diverse set of research purposes, and of types and sources of the samples. For instance, biobanks could comprise the collections of human bodily substances of all kinds, such as cells, tissues, blood, or DNA. They range in capacity from small collections of samples to large-scale national repositories. The collected samples could be population-based or disease-specific, originating from diverse profile of individuals, eg, minors or adult persons. Biobanks may contain anonymous human samples or samples linked to the specific personal information. Also, there are various purposes of biobanks, such as diagnostic, therapeutic, or research. Biobanks could be an ownership of public or private subjects, the latter being non-profit or profit based. As a consequence, such a diversity of biobanking is associated with a broad spectrum of ethical and legal issues (1-5).Ethical issues are commonly present in many aspects of biobanking. The fact that biobanks deal with human samples, invading an individual autonomy or limiting self-control, provokes a number of ethical issues. Who is actually competent to give informed consent and donate a sample? When individuals donate part of their body to a biobank, how is that human sample processed? Who is the owner of the sample? Who should decide how it should be used? Who has the right to know individual results of research? These and many more ethical dilemmas exist in the ethical framework of biobanks. With the recent rapid developments in biobanking, all of these issues are magnified with plenty of further new questions continuously arising. Ethical framework has been the most controversial issue in the domain of biobanking. Thus, it is not surprising that there is a substantial literature focusing on ethical dilemas in biobanking, such as informed consent, privacy, protection, and returning of results to participants (6-9).Due to these reasons, it is very important that researchers are provided with a current review of the literature on the ethics of biobanking in a systematic way, to document the latest consensus on ethical issues in biobanking and to highlight emerging issues. For that purpose, we reviewed the existing literature on ethical aspects of human biobanks. We aimed to develop a systematic framework for categorizing ethical concerns relevant to human biobanks and to monitor the impact of research into ethical issues. This could help the ethical boards in decision making when dealing with issues within the framework of biobanking. Moreover, we believe that such kind of work could stimulate policymakers and lawmakers to create an adequate legal framework for biobanking, an important, but still largely unregulated issue.     

Tracking of BMI,fatness and cardiorespiratory fitness from adolescence to middle adulthood: the Zagreb Growth and Development Longitudinal Study

Background: Effective intervention strategies aiming to improve cardiorespiratory fitness and to decrease body fatness are needed. However, long-term stability of these traits is not well understood.

Aim: To assess long-term tracking of cardiorespiratory fitness and body fatness from late adolescence to middle adulthood.

Subjects and methods: The sample consisted of 50 participants (31 boys) from the Zagreb Growth and Development Longitudinal Study who were followed up in adulthood (median age?=?43). Fatness was evaluated through BMI and skin-folds, while cardiorespiratory fitness was assessed using a cardiopulmonary exercise test. Inter-age partial correlation coefficients were calculated to evaluate tracking.

Results: Body mass index and skin-folds showed moderate tracking from age 15 years to middle adulthood (partial r?=?0.55, p?r?=?0.52, p?r?=?0.38, p?r?=?0.30, p?=?0.03), while ventilatory aerobic and anaerobic thresholds did not show significant tracking.

Conclusions: The results of this study indicate that preventive efforts aiming to increase cardiorespiratory fitness should include all adolescents, irrespective of their cardiorespiratory fitness status. Conversely, strategies aiming at obesity prevention should focus on high-risk groups of adolescents.     

Impact of cell death manipulation on the efficacy of photodynamic therapy-generated cancer vaccines

The main task of cancer vaccines is to deliver tumor-specific antigens to antigen-presenting cells for immune recognition that can lead to potent and durable immune response against treated tumor. Using photodynamic therapy (PDT)-generated vaccines as an example of autologous whole-cell cancer vaccines, the importance is discussed of the expression of death-associated molecules on cancer vaccine cells. This aspect appears critical for the optimal capture of vaccine cells by host’s sentinel phagocytes in order that the tumor antigenic material is processed and presented for immune recognition and elimination of targeted malignancy. It is shown that changing death pattern of vaccine cells by agents modulating apoptosis, autophagy or necrosis can significantly alter the therapeutic impact of PDT-generated vaccines. Improved therapeutic effect was observed with inhibitors of necrosis/necroptosis using IM-54, necrostatin-1 or necrostatin-7, as well as with lethal autophagy inducer STF62247. In contrast, reduced vaccine potency was found in case of treating vaccine cells with apoptosis inhibitors or lethal autophagy inhibitor spautin-1. Therefore, PDT-generated cancer vaccine cells undergoing apoptosis or lethal autophagy are much more likely to produce therapeutic benefit than vaccine cells that are necrotic. These findings warrant further detailed examination of the strategy using cell death modulating agents for the enhancement of the efficacy of cancer vaccines.     

Quantitative assessment of regional left ventricular function with cardiac MRI: three-dimensional centersurface method.

OBJECTIVES: The purpose of this study was to provide the first in vivo validation of a three-dimensional (3D) method to quantify regional left ventricular (LV) function with cardiac magnetic resonance (CMR) imaging after myocardial infarction (MI). BACKGROUND: Current cardiac methods to analyze LV function are limited by geometric assumptions and observer biases. METHODS: MI was induced percutaneously by 90-min proximal left circumflex artery balloon occlusion in 25 Yucatan minipigs. Cine and contrast-enhanced (CE) CMR imaging was performed at 5 days (n = 21) and 8 weeks (n = 22) post-MI. Twelve control animals without MI were also imaged. Regional wall thickening was measured orthogonal to the myocardial wall using the centersurface method. The left ventricle was divided into 16 segments (six basal 60 degrees , six middle 60 degrees , four apical 90 degrees ). Normal ranges for segmental wall thickness and wall thickening were defined as mean +/- 2D in control hearts. Hypokinesis was defined as a segmental thickening value below the normal range. RESULTS: Hypokinesis following MI was identified in the inferior, inferolateral and anterolateral segments when compared with controls and corresponded to areas of infarction by CE CMR. The aggregate wall thickening was also expressed as a percentage at 5 days (Infarct zone: 15% +/- 16% vs. NonInfarct zone 33% +/- 20%, P < 0.001) and 8 weeks (Infarct zone 20% +/- 20% vs. NonInfarct zone 32% +/- 22%, P < 0.001). CONCLUSIONS: The centersurface method can quantify regional wall thickening and spatially identify regions of abnormal function in 3D after MI without relying on geometric assumptions. This method may be a valuable tool to quantify regional LV function in the assessment of myocardial viability, ischemia, infarction, and the response to therapeutic interventions.     

Association of PTPN22 C1858T and CTLA-4 A49G polymorphisms with type 1 diabetes in Croatians

In this case–control study the association between the PTPN22 1858T and CTLA-4 49G gene variants and T1D in Croatian population was examined. We found that distribution of PTPN22 C1858T and CTLA-4 A49G genotypes between T1D patient (n = 102) and control (n = 193) groups differ significantly (p < 0.0001 and p = 0.012, respectively). Moreover, although the risk alleles of both SNPs are distributed more frequently in patients, the significant difference is observed only for PTPN22 1858T allele (p < 0.0001). This is therefore the first evidence that analyzed gene variants contribute to T1D pathogenesis in Croatian population.     

Self-Ligation Esthetic Brackets with Low Frictional Resistance

Objective:To test the frictional resistance forces (FRS) generated between several archwires and (1) interactive self-ligating (ISL) brackets and (2) conventionally ligated (CL) brackets.Materials and Methods:Frictional forces produced between three different archwire combinations and self-ligating (SL) brackets (ceramic and metal-slot or all-metal) and CL brackets (metal or ceramic) were evaluated in a dry environment. The three ISL brackets tested were In-Ovation-C, In-Ovation-R, and Damon 3. The three CL brackets were Mystique with Neo Clip, Clarity, and Ovation. Each bracket was tested with 0.020″ SS, 0.019″ × 0.025″ SS and 0.018″ × 0.018″ coated SS.Results:The ISL brackets generally exhibited the lowest frictional forces irrespective of the bracket material and the wire size, and CL brackets exhibited consistently higher frictional forces. Mystique with Neo Clip produced the lowest frictional resistance of all brackets. The In-Ovation-C brackets demonstrated significantly lower frictional resistance than the SL brackets In-Ovation-R and Damon 3 as well as the CL brackets Clarity and Ovation.Conclusions:The ISL ceramic brackets produced the lowest frictional resistance of all the self-ligating brackets. The CL ceramic brackets produced the greatest friction.     

Relative importance of attribute preferences for radial vs. femoral arterial access: A crowdsourcing study of healthy online‐recruited volunteers

Introduction: Percutaneous coronary intervention (PCI) is typically performed with vascular access provided by the radial or femoral artery. However, little is known about how patients value aspects of these different vascular access approaches. Methods : Conjoint analysis is a survey‐based statistical technique used in market research that helps determine how individuals value different attributes that make up a particular product or services. We utilized conjoint analysis to assess the relative importance of four attributes associated with PCI: access site, risk of bleeding, hospital stay, and radiation exposure. Participants were healthy individuals recruited by Amazon Mechanical Turk (MTURK). After completing a conjoint analysis survey, the software Conjoint.ly was used to calculate the relative importance for these four different attributes of PCI. Results : The relative importance of hospital stay, radiation exposure, bleeding risk, and procedure site was 32.7% (95% CI 29.5–35.8), 27.3% (95% CI 24.8–29.8), 24.4% (95% CI 22.3–26.5), and 15.7% (95% CI 13.6–17.8), respectively. The difference between these groups was statistically significant (P‐value < 0.00001). The difference between duration of hospital stay and radiation exposure was statistically significant (P‐value < 0.00433). Conclusion : Patients undergoing PCI place largest relative value on duration of hospital stay. Access site appears the least valued attribute. These findings carry implications to guide further research on access site choices and the consent process in the context of shared decision‐making.     

Glucose-insulin interaction in obese individuals with asymptomatic reactive hypoglycemia

Summary The interrelationship of glucose and insulin was investigated in obese nondiabetic subjects with asymptomatic reactive hypoglycemia. Results were compared to those obtained from obese control subjects and normal individuals. The diagnostic criteria for asymptomatic reactive hypoglycemia were the appearance of blood glucose values of 40 mg/dl and below during the postabsorptive phase of a 6-h OGTT and the absence of related symptoms. The blood glucose nadir occurred earlier in obese hypoglycemics than in obese controls. Maximum insulin response was similar in both obese groups, but occurred significantly later in obese hypoglycemics than in obese subjects without hypoglycemia and normal subjects. In obese hypoglycemics the blood glucose nadir was inversely proportional to the time of the insulin peak (i.e. the later the insulin peak the lower the blood glucose nadir) but correlated poorly to maximum insulin values. Delayed insulin response was found to be the major abnormality in asymptomatic reactive hypoglycemia and a probable cause of the decreased ability to maintain post-hyperglycemic glucose homeostasis. Decreased glucose tolerance in some obese hypoglycemics pre-treated with prednisolone suggests that asymptomatic reactive hypoglycemia could be the manifestation of an early diabetic stage.