Autoimmunity and Environment: Am I at risk?

The complex interplay between environmental factors and genetic susceptibility plays an essential role in disease pathogenesis. This is especially true for autoimmunity, where clinical reports, genomic and epidemiological studies, as well as animal models have identified several environmental and genetic risk factors associated with autoimmune disease. The complexity of this relationship is demonstrated by the vast array of environmental factors that have now been implicated in the induction, and possibly the maintenance of autoimmune disease. The multitude of environmental factors implicated includes both infectious and non-infectious agents. Here, we review one specific autoimmune disease, primary biliary cirrhosis (PBC), as a model for environmental risk factors acting in concert with genetic susceptibility in the disease pathogenesis. PBC is an ideal model, as both infectious and non-infectious environmental agents have been identified as risk factors, and their study provides clues for unravelling the pathogenesis of the disease.     

Customers or research participants?: Guidance for research practices in commercialization of personal genomics

Genet Med 2012:14(10):833–835     

What is a meaningful result? Disclosing the results of genomic research in autism to research participants

Developments in genomics research have been accompanied by a controversial ethical injunction: that researchers disclose individually relevant research results to research participants. With the explosion of genomic research on complex psychiatric conditions such as autism, researchers must increasingly contend with whether – and which results – to report. We conducted a qualitative study with researchers and participants involved in autism genomics research, including 4 focus groups and 23 interviews with parents of autistic children, and 23 interviews with researchers. Respondents considered genomic research results ‘reportable'' when results were perceived to explain cause, and answer the question ‘why;'' that is, respondents set a standard for reporting individually relevant genetic research results to individual participants that is specific to autism, reflecting the metaphysical value that genetic information is seen to offer in this context. In addition to this standard of meaning, respondents required that results be deemed ‘true.'' Here, respondents referenced standards of validity that were context nonspecific. Yet in practice, what qualified as ‘true'' depended on evidentiary standards within specific research disciplines as well as fundamental, and contested, theories about how autism is ‘genetic.'' For research ethics, these finding suggest that uniform and context-free obligations regarding result disclosure cannot readily be specified. For researchers, they suggest that result disclosure to individuals should be justified not only by perceived meaning but also by clarity regarding appropriate evidentiary standards, and attention to the status of epistemological debates regarding the nature and cause of disorders.     

Will it hurt less if I believe I can control it? Influence of actual and perceived control on perceived pain intensity in healthy male individuals: a randomized controlled study

We explored the effects of uncontrollability and subjective helplessness (SHL) on perceived pain intensity (PPI) in 64 healthy men randomly assigned to groups receiving controllable (C) or uncontrollable (UC) painful electric skin stimuli. SHL (d = 1.43), perceived unpleasantness (d = 1.03), and PPI (d = 0.58) were more pronounced in the UC group than in the C group. Multiple regression and bootstrap analyses for testing mediation showed a direct relationship between stressor uncontrollability and PPI (r = 0.28; P < .05), which disappeared when adjusted for the SHL increase (β = 0.49, P < .001). SHL changes were associated with objective uncontrollability (r = 0.59, P < .001). PPI and unpleasantness were positively correlated (r = 0.37, P < .01). The study suggests that the effect of objective controllability on pain intensity ratings is mediated mainly by ratings of SHL.     

Influenza A and B co-infection: a case–control study and review of the literature

Influenza virus infection remains a major cause of morbidity and mortality during winter seasons. Bacterial and virus co-infection is a commonly described situation in these patients. However, data on co-infection by influenza A and B viruses are lacking. In this study, we present the cases of co-infection by influenza A and B viruses during the winter season of 2014–2015 in our institution. We analyzed 2759 samples from 2111 patients and found that 625 samples corresponding to 609 patients were positive for influenza A or B virus. A total of 371 patients had influenza A, 228 had influenza B, and 10 (1.6 %) had influenza A and B virus detection in the same sample. The median age of co-infected patients was 78.6 years, and only one of the co-infected patients died because of the infection. Comparison with a control group of mono-infected patients revealed that co-infection was significantly associated with nosocomial acquisition [odds ratio (OR)?=?4.5, 95 % confidence interval (CI)?=?1.05–19.25, p?=?0.042]. However, co-infection was not associated with worse outcome, previous underlying condition, or vaccination status. Multivariate analysis revealed that co-infection was not an independent risk factor for death and that no single risk factor could predict co-infection.     

Periodontal infections and community-acquired pneumonia: a case–control study

The aim of this study was to evaluate if the presence of periodontal infections (PI) is associated with community-acquired pneumonia (CAP) in a group of patients admitted to a hospital. A total of 140 patients were enrolled in this case–control study, with 70 patients having CAP (case group) and the other 70 patients diagnosed with other systemic diseases (control group). A periodontal examination was carried out to assess pocket probing depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), and presence of bacterial plaque (BP). CAL and BOP showed higher scores in the case group over the control group. They were, respectively, 3.16?±?2.43 mm and 0.33?±?0.24 % for the case group, and 1.99?±?2.23 mm and 0.25?±?0.24 % for the control group (p?<?0.05). High scores for BP were observed in both groups (case: 97.1 %; control: 98.6 %, p?=?1.0000). Chronic periodontitis (CP) was more frequent in patients with CAP (case: 61.4 %; control: 41.4 %). The presence of moderate or severe CP increased the risk for CAP [odds ratio (OR)?=?4.4, 95 % confidence interval (CI)?=?1.4–13.8], even when adjusted for age, ethnicity, gender, and smoking. Moderate and severe chronic periodontitis were associated with CAP in this study.     

The who,what, and why of research participants’ intentions to request a broad range of secondary findings in a diagnostic genomic sequencing study

PurposeIn a diagnostic exome sequencing study (the North Carolina Clinical Genomic Evaluation by Next-Generation Exome Sequencing project, NCGENES), we investigated adult patients’ intentions to request six categories of secondary findings (SFs) with low or no medical actionability and correlates of their intentions.MethodsAt enrollment, eligible participants (n = 152) completed measures assessing their sociodemographic, clinical, and literacy-related characteristics. Prior to and during an in-person diagnostic result disclosure visit, they received education about categories of SFs they could request. Immediately after receiving education at the visit, participants completed measures of intention to learn SFs, interest in each category, and anticipated regret for learning and not learning each category.ResultsSeventy-eight percent of participants intended to learn at least some SFs. Logistic regressions examined their intention to learn any or all of these findings (versus none) and interest in each of the six individual categories (yes/no). Results revealed little association between intentions and sociodemographic, clinical, or literacy-related factors. Across outcomes, participants who anticipated regret for learning SFs reported weaker intention to learn them (odds ratios (ORs) from 0.47 to 0.71), and participants who anticipated regret for not learning these findings reported stronger intention to learn them (OR 1.61–2.22).ConclusionIntentions to request SFs with low or no medical actionability may be strongly influenced by participants’ desire to avoid regret.     

The perceptual control of goal-directed locomotion: a common control architecture for interception and navigation?

Intercepting a moving object while locomoting is a highly complex and demanding ability. Notwithstanding the identification of several informational candidates, the role of perceptual variables in the control process underlying such skills remains an open question. In this study we used a virtual reality set-up for studying locomotor interception of a moving ball. The subject had to walk along a straight path and could freely modify forward velocity, if necessary, in order to intercept—with the head—a ball moving along a straight path that led it to cross the agents displacement axis. In a series of experiments we manipulated a local (ball size) and a global (focus of expansion) component of the visual flow but also the egocentric orientation of the ball. The experimental observations are well captured by a dynamic model linking the locomotor acceleration to properties of both global flow and egocentric direction. More precisely the changes in locomotor velocity depend on a linear combination of the change in bearing angle and the change in egocentric orientation, allowing the emergence of adaptive behavior under a variety of circumstances. We conclude that the mechanisms underlying the control of different goal-directed locomotion tasks (i.e. steering and interceptive tasks) could share a common architecture.     

How does the collection of genetic test results affect research participants?

The collection of genetic test results has become routine in clinical research. Yet, there are few data on the impact of this practice. The present study provides the first empirical data that we are aware of on the impact this practice has on research participants. The findings suggest that collection of genetic test results in the research setting increases many individuals' desire to know the results themselves. Some respondents attributed this effect to the fact that the data existed, while others did not want investigators to have information about them that they did not possess. A smaller proportion of respondents assumed that investigators who had collected genetic test results would monitor their clinical significance over time. These respondents were less inclined to want to know their genetic test results once an investigator was aware of them. Investigators and IRBs should recognize these phenomena and address them in the design and conduct of studies which collect genetic information.     

Transitions in a postural task: do the recruitment and suppression of degrees of freedom stabilize posture?

In this study, we examined flexibility in postural coordination by inducing transitions between postural patterns. Previous work demonstrated that the postural control system produces two task-specific postural patterns as a function of the frequency of support surface translation. For slow translation frequencies (<0.5 Hz), subjects ride on the platform reminiscent of upright stance (ride pattern), and for fast frequencies (≥0.75 Hz) subjects actively fixed the head and trunk in space (head fixed pattern) during anterior-posterior platform motion. To study the adaptation of the postural control system, we had subjects stand on a support surface undergoing increases (from 0.2 to 1.0 Hz in 0.1-Hz steps) and decreases (from 1.0 to 0.2 Hz in 0.1-Hz steps) in translation frequency with the eyes open and closed. Kinematic measures of sagittal plane body motion revealed a gradual transition between these two postural patterns as a function of frequency scaling. In both the increasing and decreasing frequency conditions with visual input, center of mass displacements gradually decreased and increased, respectively, whereas upper-trunk (and head) displacement decreased gradually within the ride pattern until a head fixed pattern was observed without any significant changes in displacement for translation frequencies at and above 0.6 Hz. Without visual input, the scaling of the ride pattern was similar except the transition to the head fixed pattern never emerged with increasing frequency; instead, a less stable pattern exhibiting slow drift in head-trunk anterior-posterior motion (drift pattern) was observed at and above 0.5 Hz oscillations. The stability of the head fixed pattern at fast frequencies was clearly dependent on visual input suggesting that vision was more critical for trunk and head control in space at high than low translation frequencies. Head velocity was kept constant, and lower with vision, as translation frequency (and velocity) changed suggesting a head velocity threshold constraint across postural patterns. The gradual transition from the ride to the head fixed pattern was made possible by the recruitment of available degrees of freedom in the form of ankle, then knee, and then hip joint motion. In turn, the transition from the head fixed or drift pattern was made possible by the gradual suppression of available degrees of freedom in the form of reducing hip, then knee, and then ankle motion. The gradual change in postural kinematics without instabilities and hysteresis suggests that the ability to recruit and suppress biomechanical degrees of freedom allows the postural control system to gradually change postural strategies without suffering a loss of stability. The results are discussed in light of possible self-organizing mechanisms in the multisensory control of posture. Electronic Publication     

HLA DR/DQ alleles and risk of type I diabetes in childhood: a population–based case–control study

Abstract The objective was to evaluate HLA DR/DQ alleles and their risk factor for type 1 diabetes in the Abruzzo region (central Italy). Sixty incident cases from the Abruzzo region were studied together with 120 unrelated control subjects living in the same administrative areas. The relative risk of diabetes associated with the alleles under study was calculated by deriving the odds ratio (OR) maximum likelihood estimates and their 95% confidence intervals (CI) by the exponentiation of the logistic regression beta–parameter. The combination DRB1*03/DQA1*0501/DQB1*0201 was found in 20.0% of patients and 7.1% of the control subjects, conferring an OR of 4.04 and a CI of 1.97–8.49. The combination DRB1*04/DQA1*0301/DQB1*0302 was found in 23.3% of diabetic patients and 6.7% of controls, giving an OR of 5.69 and a CI of 2.77–12.05. DRB1*11/DQA1*0505/DQB1*0301 and DQA1*0505/DQB1*0301 were negatively associated with type 1 diabetes (OR=0.27, CI 0.11–0.57; OR=0.07, CI 0.02–0.19). The DQA1 genotype at risk was found to be DQA1*0301/DQA1*0501: OR=23.80, CI 2.97–190.89, as it occurred with the highest frequency in the patient group. The DQB1 genotype at risk was found to be DQB1*0201/DQB1*0302, which occurred in 13.3% of patients but in only 1.1% of the control group (OR=29.75, CI 5.36–549.25). Our results shed further light on the risk of development of this disease during a specific time period in an area where the overall incidence of type 1 diabetes is known.     

Use of next generation sequencing technologies in research and beyond: are participants with mental health disorders fully protected?

Background

Interest in biobanking for collection of specimens for non-communicable diseases research has grown in recent times. This paper explores the perspectives of Nigerians on donation of specimen for the biobanking research.

Methods

We conducted 16 Focus Group Discussions (FGD) with individuals from different ethnic, age and socio-economic groups in Kano (North), Enugu (Southeast), Oyo States (Southwest) and Abuja, the Federal Capital Territory (Central) of Nigeria. We used topic guides and prompt statements to explore the knowledge and understanding of interviewees to general issues about biobanking of biospecimens, their use and specifically about role of biobanking in non-communicable diseases research.

Results

A total of 123 individuals participated in 16 focus group discussions in 2011. Our participants had limited knowledge of the concept of biobanking but accepted it once they were educated about it and saw it as a worthwhile venture. Half of our study participants supported use of broad consent, a quarter supported restricted consent while the remaining quarter were in favour of tiered consent. Most discussants support shipment of their samples to other countries for further research, but they prefer those collaborations to be done only with competent, ethical researchers and they would like to receive feedback about such projects. The majority preferred health care as a benefit from participation, particularly for any unexpected condition that may be discovered during the course of the research instead of financial compensation. Participants emphasized the need to ensure that donated samples were not used for research that contradicts their religious beliefs.

Conclusions

Our study demonstrates that our participants accepted biobanking once they understand it but there were different attitudes to elements of biobanking such as type of consent. Our study highlights the need to carefully document population attitudes to elements of modern scientific research and the consenting process.     

Polymicrobial pneumococcal bacteraemia: a case–control study

European Journal of Clinical Microbiology & Infectious Diseases - Polymicrobial bacteraemia involving Streptococcus pneumoniae and other bacteria (e.g. Escherichia coli, Staphylococcus aureus,...     

Gene and cancer therapy--pseudorabies virus: a novel research and therapeutic tool?

The past decade has been marked by significant advances in the application of gene transfer into living cells of animals and humans, with the resulting catapulting of preclinical and basic scientific concepts into therapeutic trials. A variety of virus-mediated gene delivery techniques have proved to be superior to other methodologies. This article concisely reviews the current status of gene and tumor therapy, focusing on virus-based technologies, describes the molecular biology of neurotropic herpesviruses and the application of herpes simplex virus, a relative of pseudorabies virus (PRV) in gene transfer and cancer therapy protocols. Finally, it addresses the issue of whether PRV, a nonhuman pathogen, could serve as a suitable research and therapeutic tool as concerns genetic and tumor therapy.     

At the centre of a science of psychopathology? Characteristics and limitations of cognitive research

In this brief paper I will suggest that the cognitive approach has four characteristics which must place it at the centre of any complete science of psychopathology: (1) it leads to testable hypotheses about abnormal mental states; (2) it establishes a link between normal psychology and abnormal mental processes, and therefore obviates the need to dichotomise behaviour into the normal and the abnormal; (3) it has the potential to make apparently bizarre and irrational behaviour understandable; and (4) it is neutral with regard to the relative contributions that biology and the environment make to the aetiology of psychiatric disorders. I also identify three limitations of contemporary cognitive models of psychiatric disorders: (1) an over-reliance on conventional methods of psychiatric classification; (2) an underemphasis on social aspects of cognition; and (3) a failure to integrate findings obtained from different models. Once these limitations are overcome, cognitive research is likely to lead to a revolution in our understanding of abnormal behaviour.     

Polymorphisms of methylenetetrahydrofolate reductase and methionine synthase genes and bladder cancer risk: a case–control study with meta-analysis

Folate deficiency due to the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) variants leads to carcinogenesis by affecting DNA synthesis, repair, and methylation. We hypothesized that the MTHFR C677T, A1298C, and MS A2756G polymorphisms are associated with risk of bladder cancer. In a case-control study of 239 bladder cancer cases and 250 cancer-free controls, we found that the MTHFR 677TT genotype was statistically significantly associated with an increased risk of bladder cancer compared with the 677CC genotype (OR = 2.06, 95% CI = 1.16-3.64). Furthermore, the TA haplotype was associated with a significantly increased bladder cancer risk (OR = 1.38, 95% CI = 1.05-1.81) than was the most common haplotype, CA (e.g., CA denotes MTHFR 677C -1298A). We also found that the combined genotypes with 4-6 variant (risk) alleles (i.e., MTHFR 677T, 1298A, and MS 2756G alleles) were associated with an increased risk of bladder cancer (OR = 1.62, 95% CI = 1.03-2.53) compared with those with 0-3 variants, and this increased risk was more pronounced among subgroup of older people (OR = 1.71, 95% CI = 1.03-2.83). A meta-analysis of seven studies did not show a significant risk of bladder cancer in the MTHFR polymorphisms. The MTHFR polymorphisms and their haplotypes appear to jointly contribute to risk of bladder cancer.     

Scared to lose control? General and health locus of control in females with a phobia of vomiting

The term emetophobia (i.e., a fear of vomiting) exists as rather an elusive predicament, often eluding conventional treatment. The present study involved 149 participants, consisting of 51 emetophobics, 48 phobic controls (i.e. those who suffered from a different phobia), and 50 nonphobic controls. Participants were administered the Rotter (1966) Locus of Control Scale and the Health Locus of Control Scale by B.S. Wallston, Wallston, Kaplan, and Maides (1976). Significant differences were found among the three groups; specifically, that emetophobics had a significantly higher internal Locus of Control Scale score with regard to both general and health-related issues than did the two control groups. It is suggested that vomiting phobics may have a fear of losing control, and that their vomiting phobia is reflective of this alternative, underlying problem. More research is required to explore the association between emetophobia and issues surrounding control; however, the current study suggests that it may be helpful for therapists to consider this aspect when treating a patient with vomiting phobia.