Replication of the association of GLT6D1 with aggressive periodontitis in a Sudanese population

BACKGROUND: Susceptibility to aggressive periodontitis (AgP) is influenced by genetic as well as environmental factors. Studies linking gene variants to AgP have been mainly centred in developed countries with limited data from Africa.
AIM: To investigate whether previously reported candidate gene associations with AgP could be replicated in a population from Sudan.


METHODS: The investigation was a case-control design. Cases with AgP (n = 132) and controls (n = 136) were identified from patients attending the Periodontal Department in Khartoum Dental Hospital. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Analysis focused on gene variants with a minor allele frequency (MAF) > 25% in the Sudanese subjects that had previously been reported to be associated with AgP.


RESULTS: One candidate gene rs1537415 (GLT6D1) was significantly associated with AgP, OR = 1.50 (95% CI 1.04-2.17), p = 0.0295 (increasing to p = 0.09 after correction for multiple testing). The association strengthened to OR = 1.56 (95% CI 1.15-2.16), p = 0.0042 when the controls were supplemented with data from the Hap map for the Yoruba in Ibadan (n = 147) and remained significant (p = 0.013) after correction for multiple testing.


CONCLUSION: The study independently replicated the finding that rs1537415, a variant in glycosyl transferase gene GLT6D1, is associated with AgP and provided the first report of genetic associations with AgP in a Sudanese population.

On the antioxidant properties of erythropoietin and its association with the oxidative-nitrosative stress response to hypoxia in humans

Aim: The aim of this study was to examine if erythropoietin (EPO) has the potential to act as a biological antioxidant and determine the underlying mechanisms.

Methods: The rate at which its recombinant form (rHuEPO) reacts with hydroxyl (HO center dot), 2,2-diphenyl-1-picrylhydrazyl (DPPH center dot) and peroxyl (ROO center dot) radicals was evaluated in-vitro. The relationship between the erythopoietic and oxidative-nitrosative stress response to poikilocapneic hypoxia was determined separately in-vivo by sampling arterial blood from eleven males in normoxia and following 12 h exposure to 13% oxygen. Electron paramagnetic resonance spectroscopy, ELISA and ozone-based chemiluminescence were employed for direct detection of ascorbate (A(center dot-)) and N-tert-butyl-a-phenylnitrone spin-trapped alkoxyl (PBN-OR) radicals, 3-nitrotyrosine (3-NT) and nitrite (NO2-).

Results: We found rHuEPO to be a potent scavenger of HO center dot (k(r) = 1.03-1.66 x 10(11) M-1 s(-1)) with the capacity to inhibit Fenton chemistry through catalytic iron chelation. Its ability to scavenge DPPH. and ROO center dot was also superior compared to other more conventional antioxidants. Hypoxia was associated with a rise in arterial EPO and free radical-mediated reduction in nitric oxide, indicative of oxidative-nitrosative stress. The latter was confirmed by an increased systemic formation of A(center dot-), PBN-OR, 3-NT and corresponding loss of NO2- (P <0.05 vs. normoxia). The erythropoietic and oxidative-nitrosative stress responses were consistently related (r =-0.52 to 0.68, P <0.05).

Conclusion: These findings demonstrate that EPO has the capacity to act as a biological antioxidant and provide a mechanistic basis for its reported cytoprotective benefits within the clinical setting.

Advanced design optimization of cold-formed steel portal frame buildings

The design optimization of cold-formed steel portal frame buildings is considered in this paper. The objective function is based on the cost of the members for the main frame and secondary members (i.e., purlins, girts, and cladding for walls and roofs) per unit area on the plan of the building. A real-coded niching genetic algorithm is used to minimize the cost of the frame and secondary members that are designed on the basis of ultimate limit state. It iis shown that the proposed algorithm shows effective and robust capacity in generating the optimal solution, owing to the population's diversity being maintained by applying the niching method. In the optimal design, the cost of purlins and side rails are shown to account for 25% of the total cost; the main frame members account for 27% of the total cost, claddings for the walls and roofs accounted for 27% of the total cost.

Recent Developments in the Law of Torts in Northern Ireland Annual Conference of the Irish Association of Law Teachers

This paper reviews decisions from the Northern Ireland and England and Wales High Courts and Courts of Appeal as well as the UK Supreme Court relating to tort and principally to the tort of negligence in the past 12 months or so.

In structure, the paper will be presented in four parts. First, three preliminary points relating to contemporary features of the NI civil courts: personal litigants – Devine v McAteer [2012] NICA 30 (7 September 2012); pre-action protocols – Monaghan v Graham [2013] NIQB 53 (3 May 2013); and the rise of alternative dispute resolution. On the last named issue, the recent decision of PGF II SA v OMFS Company 1 Ltd [2013] EWCA Civ 1288 (23 October 2013) on unreasonable refusal to mediate, will be discussed.

Second, the paper moves to consider the law of negligence generally and case law from the NI High Court reiterating Lord Hoffmann’s view in Tomlinson v Congleton Borough Council [2004] 1 AC 46 that no duty of care arises from obvious risks of injury. In this, reference will be made to the application of the above “Hoffmann principle” in West Sussex County Council v Pierce [2013] EWCA Civ 1230 (16 October 2013), which concerned an accident sustained by a child at school. A similar set of facts was presented recently to the UK Supreme Court in Woodland v Essex County Council [2013] UKSC 66 (23 October 2013). The decision there, on non-delegable duties of care, will have a significant impact for schools in the provision of extracurricular activities.

Third, I will review a NI case of note on the duty of care of solicitors in the context of professional negligence in the context of conflicting advice by counsel.

Fourth, I will examine a series of cases on employer liability and including issues such as the duty of care towards the volunteer worker; tort and safety at work principles generally; and, more specifically, the duty of care of the employer towards an employee who suffers psychiatric illness as a result of stress and/or harassment at work. On the issue of workplace stress, the NI courts have made extensive reference to the Hale LJ principles found in the Court of Appeal decision of Hatton v Sutherland [2002] 1 All ER 1 and applied to those who have suffered trauma in reporting on or policing “the troubles” in Northern Ireland. On the issue of statutory harassment at work, the paper will also mention the UK Supreme Court’s decision in Hayes v Willoughby [2013] UKSC 17 (20 March 2013).

Inhibition of cellular proliferation by the Wilms tumor suppressor WT1 requires association with the inducible chaperone Hsp70

The Wilms tumor suppressor WT1 encodes a zinc finger transcription factor that is expressed in glomerular podocytes during a narrow window in kidney development. By immunoprecipitation and protein microsequencing analysis, we have identified a major cellular protein associated with endogenous WT1 to be the inducible chaperone Hsp70. WT1 and Hsp70 are physically associated in embryonic rat kidney cells, in primary Wilms tumor specimens and in cultured cells with inducible expression of WT1. Colocalization of WT1 and Hsp70 is evident within podocytes of the developing kidney, and Hsp70 is recruited to the characteristic subnuclear clusters that contain WT1. The amino-terminal transactivation domain of WT1 is required for binding to Hsp70, and expression of that domain itself is sufficient to induce expression of Hsp70 through the heat shock element (HSE). Substitution of a heterologous Hsp70-binding domain derived from human DNAJ is sufficient to restore the functional properties of a WT1 protein with an amino-terminal deletion, an effect that is abrogated by a point mutation in DNAJ that reduces binding to Hsp70. These observations indicate that Hsp70 is an important cofactor for the function of WT1, and suggest a potential role for this chaperone during kidney differentiation.

Association of common gene variants in the WNT/β-catenin pathway with colon cancer recurrence

Wnt/β-catenin signaling has a central role in the development and progression of most colon cancers (CCs). Germline variants in Wnt/β-catenin pathway genes may result in altered gene function and/or activity, thereby causing inter-individual differences in relation to tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of Wnt/β-catenin pathway genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II CC. A total of 234 patients treated with 5-fluorouracil-based chemotherapy were included in this study. Whole-blood samples were analyzed for putative functional germline polymorphisms in SFRP3, SFRP4, DKK2, DKK3, Axin2, APC, TCF7L2, WNT5B, CXXC4, NOTCH2 and GLI1 genes by PCR-based restriction fragment-length polymorphism or direct DNA sequencing. Polymorphisms with statistical significance were validated in an independent study cohort. The minor allele of WNT5B rs2010851 T>G was significantly associated with a shorter TTR (10.7 vs 4.9 years; hazard ratio: 2.48; 95% CI, 0.96-6.38; P=0.04) in high-risk stage II CC patients. This result remained significant in multivariate Cox's regression analysis. This study shows that the WNT5B germline variant rs2010851 was significantly identified as a stage-dependent prognostic marker for CC patients after 5-fluorouracil-based adjuvant therapy.

Defining consensus norms for palliative care of people with intellectual disabilities in Europe using Delphi methods: A White Paper from the European Association of Palliative care

Background: People with intellectual disabilities often present with unique challenges that make it more difficult to meet their
palliative care needs.
Aim: To define consensus norms for palliative care of people with intellectual disabilities in Europe.
Design: Delphi study in four rounds: (1) a taskforce of 12 experts from seven European countries drafted the norms, based on available empirical knowledge and regional/national guidelines; (2) using an online survey, 34 experts from 18 European countries evaluated the draft norms, provided feedback and distributed the survey within their professional networks. Criteria for consensus
were clearly defined; (3) modifications and recommendations were made by the taskforce; and (4) the European Association for
Palliative Care reviewed and approved the final version.
Setting and participants: Taskforce members: identified through international networking strategies. Expert panel: a purposive sample identified through taskforce members’ networks.
Results: A total of 80 experts from 15 European countries evaluated 52 items within the following 13 norms: equity of access, communication, recognising the need for palliative care, assessment of total needs, symptom management, end-of-life decision making, involving those who matter, collaboration, support for family/carers, preparing for death, bereavement support, education/training
and developing/managing services. None of the items scored less than 86% agreement, making a further round unnecessary. In light of respondents’ comments, several items were modified and one item was deleted.
Conclusion: This White Paper presents the first guidance for clinical practice, policy and research related to palliative care for people with intellectual disabilities based on evidence and European consensus, setting a benchmark for changes in policy and practice.

Association of a Mediterranean type diet with age-related macular degeneration in the EUREYE study

Investigative Ophthalmology & Visual Science Volume 56 Issue 7 Pages 3760-3760