An Appeal to the Global Health Community for a Tripartite Innovation: An "Essential Diagnostics List," "Health in All Policies," and "See-Through 21(st) Century Science and Ethics".

Diagnostics spanning a wide range of new biotechnologies, including proteomics, metabolomics, and nanotechnology, are emerging as companion tests to innovative medicines. In this Opinion, we present the rationale for promulgating an "Essential Diagnostics List." Additionally, we explain the ways in which adopting a vision for "Health in All Policies" could link essential diagnostics with robust and timely societal outcomes such as sustainable development, human rights, gender parity, and alleviation of poverty. We do so in three ways. First, we propose the need for a new, "see through" taxonomy for knowledge-based innovation as we transition from the material industries (e.g., textiles, plastic, cement, glass) dominant in the 20(th) century to the anticipated knowledge industry of the 21st century. If knowledge is the currency of the present century, then it is sensible to adopt an approach that thoroughly examines scientific knowledge, starting with the production aims, methods, quality, distribution, access, and the ends it purports to serve. Second, we explain that this knowledge trajectory focus on innovation is crucial and applicable across all sectors, including public, private, or public-private partnerships, as it underscores the fact that scientific knowledge is a co-product of technology, human values, and social systems. By making the value systems embedded in scientific design and knowledge co-production transparent, we all stand to benefit from sustainable and transparent science. Third, we appeal to the global health community to consider the necessary qualities of good governance for 21st century organizations that will embark on developing essential diagnostics. These have importance not only for science and knowledge-based innovation, but also for the ways in which we can build open, healthy, and peaceful civil societies today and for future generations.

Modified sequential Helicobacter pylori eradication therapy using high dose omeprazole and amoxicillin in the initial phase in the extensive metaboliser Turkish patients for CYP2C19 polymorphism is ineffective.

AIM: To investigate whether the sequential therapy composed of high dose omeprazole and high dose amoxicillin in the first step was effective in eradication of H. pylori and whether there was a relation between effectiveness of the therapy and CYP2C19 gene polymorphism. METHOD: 134 dyspeptic patients with H. pylori were administered a modified sequential therapy composed of omeprazole 40 mg t.i.d. and amoxicillin 1000 mg t.i.d, for the first five days followed by omeprazole 20 mg b.d., metronidazole 500 mg t.i.d. and tetracycline 500 mg t.i.d, for the next five days. CYP2C19 genotype status was determined in patients. Hp eradication status was investigated by C14 UNT four weeks after treatment. RESULTS: The eradication rates were 64.9% in ITT and 74.3% in PP analysis. In subgroup analyses, eradication rates were 73.8% and 60.8% (p: 0.145) in ITT for peptic ulcer and non-ulcer dyspepsia patients respectively and 86.1% and 69.1% (p: 0.052) in PP analysis for peptic ulcer and non-ulcer dyspepsia patients respectively. The difference was not significant. As for the CYP2C19 gene status, 81.5% of the patients had HoEM and 17.3% of the patients had HeEM, and eradication rates were 72% and 75% in ITT analysis for HoEM and HeEM respectively (p: 0.803) and 73.9% and 85.7% in PP analysis for HoEM and HeEM respectively (p: 0.347). There was not a significant difference in H. pylori eradication rates between the two groups. CONCLUSION: This modified high-dose sequential therapy was ineffective in a Turkish sample, nearly all of whom had EM in terms of CYP2C19 gene status.

Association of (-1,607) 1G/2G polymorphism of matrix metalloproteinase-1 gene with knee osteoarthritis in the Turkish population (knee osteoarthritis and MMPs gene polymorphisms).

The aim of this study was to investigate whether functional polymorphisms in the promoter of matrix metalloproteinase-1 (MMP-1), MMP-2 and MMP-9 genes were associated with susceptibility to knee osteoarthritis in the Turkish population. The MMP-1 -1,607 1G/2G (rs1799750), MMP-2 -1,306 C/T (rs243865), and MMP-9 -1,562 C/T (rs3918242) polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism assay in 157 patients diagnosed with knee osteoarthritis based on the criteria of American College of Rheumatology and in 84 controls in Mersin, Turkey. Genotype distributions and allele frequencies of MMP-1, MMP-2, and MMP-9 gene polymorphisms were compared between the patients and controls. There were significant differences between the groups regarding the genotype distribution of MMP-1 polymorphism (P = 0.001). The frequencies of 1G/1G and 1G/2G genotypes were significantly higher in the knee osteoarthritis than in the controls (P = 0.002, and P = 0.006, respectively). In addition, 1G allele frequency of MMP-1 gene was higher in the patients than in the control group (P = 0.0001). The genotype distributions and allele frequencies of MMP-2 and MMP-9 gene polymorphisms did not differ between the osteoarthritis and the control groups (P > 0.05). These findings suggest that the -1,607 1G/2G polymorphism in the MMP-1 gene may contribute to susceptibility to knee osteoarthritis in the Turkish population.

Lack of association between DRD3 gene polymorphism and response to clozapine in Turkish schizoprenia patients.

It is hypothesized that molecular components of dopaminergic system, especially the dopamine D3 receptor gene (DRD3), may play a crucial role in the pathophysiology of schizophrenia, because it is abundant in the limbic system of the brain and it binds antipsychotic drugs. Several groups attempted to find an association between a serine-to-glycine polymorphism of the DRD3 gene (Ser9Gly) and schizophrenia; however, the results were inconsistent. In this study, we aimed to investigate the relationship of the Serine/Glycine polymorphism of the DRD3 gene with therapeutic response to clozapine treatment between Turkish schizophrenia patients (N = 92) and healthy controls (N = 100). Genotype groups were comparable in BPRS, SAPS, SANS analysis of response to clozapine. Our results suggest that an association between the Ser/Gly polymorphism of DRD3 gene and response to clozapine in Turkish schizophrenia patients is unlikely to exist.

Lack of association polymorphisms of the IL1RN, IL1A, and IL1B genes with knee osteoarthritis in Turkish patients.

PURPOSE: To examine whether polymorphisms of the interleukin 1 receptor antagonist (IL1RN), interleukin 1 alpha (IL1A) and interleukin 1 beta (IL1B) genes are markers of genetic susceptibility to knee osteoarthritis in Turkish patients. METHODS: One hundred and seven patients with knee osteoarthritis and 67 controls were studied. Three polymorphisms of IL1A, IL1B, and IL1RN genes were typed from genomic DNA. Allelic frequencies were compared between patients and control subjects. RESULTS: No significant differences were observed in genotype and allele frequencies of the IL1RN VNTR, IL1A+4845, IL1B+3953 genes polymorphisms between patients and controls. Furthermore, we did not detect any association genotypes of the polymorphisms with the clinical, radiological, and laboratory profiles of patients. CONCLUSIONS: The present study suggest that the IL1RN VNTR, IL1A+4845, IL1B+3953 genes polymorphisms are not genetic markers of susceptibility to knee osteoarthritis in Turkish patients, and are unrelated to the clinical, radiological, and laboratory characteristics of knee osteoarthritis.