Healthy Eating in Jamaica: The Cost Factor.

OBJECTIVE: This study was conducted to determine the importance of food cost in securing a healthy diet to combat non-communicable diseases. Several studies have evaluated whether healthier foods or diets cost more but a full range of health criteria has rarely been explored. Rather than merely comparing high and low energy dense foods, this study also included type of fat, vitamin, mineral and fibre content of foods in classifying them as healthy and less healthy. METHOD: Both 'commonly consumed' and 'all available' foods were ranked according to their nutritional value and potential positive or negative contribution to the development of major health problems in Jamaica such as obesity and chronic diseases. The costs of 158 food items were averaged from supermarkets, municipal markets and wholesale outlets in six parishes across Jamaica. Cost differentials were then assessed in comparing healthy and less healthy foods. RESULTS: The study found that among the commonly consumed foods in Jamaica, healthy options cost J$88 (US$0.78) more than less healthy ones. However, when all the available food items were considered, the less healthy options cost more. The cheapest daily cost of a nutritionally balanced diet in Jamaica varied considerably by parish but was on average J$269 (US$2.40) per person. For a family of three, this translates approximately to the total minimum wage per week. CONCLUSION: Eating healthy in Jamaica can be achieved at low cost if appropriate information on nutrient content/value for money is provided to consumers. Effective promotions by public and private sector agencies are essential for consumer choice to be optimal.

Enrichment of vitamin D response elements in RA-associated loci supports a role for vitamin D in the pathogenesis of RA.

The aim of this study was to explore the role of vitamin D in rheumatoid arthritis (RA) pathogenesis by investigating the enrichment of vitamin D response elements (VDREs) in confirmed RA susceptibility loci and testing variants associated with vitamin D levels for association with RA. Bioinformatically, VDRE genomic positions were overlaid with non-HLA (human leukocyte antigen)-confirmed RA susceptibility regions. The number of VDREs at RA loci was compared to a randomly selected set of genomic loci to calculate an average relative risk (RR). Single-nucleotide polymorphisms (SNPs) in the DHCR7/NADSYN1 (nicotinamide adenine dinucleotide synthase 1) and CYP2R1 loci, previously associated with circulating vitamin D levels, were tested in UK RA cases (n=3870) and controls (n=8430). Significant enrichment of VDREs was seen at RA loci (P=9.23 × 10(-8)) when regions were defined either by gene (RR 5.50) or position (RR 5.86). SNPs in the DHCR7/NADSYN1 locus showed evidence of positive association with RA, rs4944076 (P=0.008, odds ratio (OR) 1.14, 95% confidence interval (CI) 1.03-1.24). The significant enrichment of VDREs at RA-associated loci and the modest association of variants in loci-controlling levels of circulating vitamin D supports the hypothesis that vitamin D has a role in the development of RA.

A genetic marker at the OLIG3/TNFAIP3 locus associates with methotrexate continuation in early inflammatory polyarthritis: results from the Norfolk Arthritis Register.

Whole-genome association studies in rheumatoid arthritis have identified single-nucleotide polymorphisms (SNPs) predisposing to disease with moderate risk. We aimed to investigate the role of these markers in predicting methotrexate (MTX) response, measured by continuation on MTX monotherapy in patients with recent onset inflammatory polyarthritis (IP). In all, 19 SNPs were genotyped in 736 patients treated with MTX following registration, or not more than 3 months before registration, to the Norfolk Arthritis Register. The association of SNPs with MTX continuation by year 1 and by year 2 was investigated using Cox proportional hazard regression models. A SNP within the OLIG3/TNFAIP3 locus (rs6920220) was associated with being less likely to maintain MTX monotherapy at year 1, hazards ratio (HR) 1.73 (1.18, 2.52) and year 2, HR 1.49 (1.11, 2.00); correlating with an increased in adverse events. Weak evidence for an effect at the PTPN22 locus was also observed. These findings require replication in other large datasets.

Examining the overlap between genome-wide rare variant association signals and linkage peaks in rheumatoid arthritis.

OBJECTIVE: With the exception of the major histocompatibility complex (MHC) and STAT4, no other rheumatoid arthritis (RA) linkage peak has been successfully fine-mapped to date. This apparent failure to identify association under peaks of linkage could be ascribed to the examination of common variation, when linkage is likely to be driven by rare variants. The purpose of this study was to investigate the overlap between genome-wide rare variant RA association signals observed in the Wellcome Trust Case Control Consortium (WTCCC) study and 11 replicating RA linkage peaks, defined as regions with evidence for linkage in >1 study. METHODS: The WTCCC data set contained 40,482 variants with minor allele frequency of ≤0.05 in 1,860 RA patients and 2,938 controls. Genotypes of all rare variants within a given gene region were collapsed into a single locus and a global P value was calculated per gene. RESULTS: The distribution of rare variant signals (association P≤10(-5)) was found to differ significantly between regions with and without linkage evidence (P=2×10(-17) by Fisher's exact test). No significant difference was observed after data from the MHC region were removed or when the effect of the HLA-DRB1 locus was accounted for. CONCLUSION: The results suggest that rare variant association signals are significantly overrepresented under linkage peaks in RA, but the effect is driven by the MHC. This is the first study to examine the overlap between linkage peaks and rare variant association signals genome-wide in a complex disease.

HLA-DPB1-COL11A2 and three additional xMHC loci are independently associated with RA in a UK cohort.

The aim of this study was to investigate the complex association pattern of the extended major histocompatibility complex (xMHC) region with rheumatoid arthritis (RA) susceptibility to identify effects independent of HLA-DRB1. A total of 1804 RA cases and 1474 controls were included. High-resolution HLA-DRB1 typing was performed. Subjects were genotyped for 1546 single-nucleotide polymorphisms (SNPs) using Affymetrix GeneChip 500 K (Santa Clara, CA, USA) as part of the Wellcome Trust Case Control Consortium Study. Statistical analysis was carried out using PLINK. To avoid confounding by RA-associated HLA-DRB1 alleles, we analyzed xMHC SNPs using a data set with pairwise matching of cases and controls on DRB1 genotypes. A total of 594 case-control pairs with identical DRB1 genotypes were identified. After this adjustment, 104 SNPs remained significantly associated with RA (P<0.05), suggesting that additional RA loci independent of HLA-DRB1 can be found in the xMHC region. Of these, four loci showed the strongest associations with RA (P<0.005): ZNF391, the olfactory receptor (OR) gene cluster, C6orf26-RDBP and HLA-DPB1-COL11A2. An additional locus mapping to the BTN (butyrophilin) cluster showed independent association with RA in anti-cyclic citrullinated peptide-positive patients exclusively. We have validated the previously described independent association of the HLA-DPB1-COL11A2 locus with RA. In addition, association with three novel independent RA loci in the xMHC region (ZNF391, OR2H1 and C6orf26-RDBP) has been detected.

A systematic investigation of confirmed autoimmune loci in early-onset psoriasis reveals an association with IL2/IL21.

BACKGROUND: Many autoimmune diseases share common susceptibility loci suggesting similar underlying cellular mechanisms involved in disease expression. OBJECTIVES: The purpose of this investigation was to study 21 genetic variants in 14 genes that are confirmed autoimmune loci in a cohort of patients with early-onset psoriasis. METHODS: Patients with early-onset psoriasis (n = 750) and controls (n = 3531) were genotyped using the Sequenom(®) MassArray™ iPLEX Gold platform. RESULTS: We found strong evidence of association with two variants in the IL2/IL21 (rs6822844, genotypic P = 3·3 × 10(-4) ; rs2069778, genotypic P = 7·86 × 10(-4)) region. CONCLUSIONS: The findings, although requiring replication, suggest that IL2/IL21 may play a key role in the pathogenesis of psoriasis as well as in other diverse autoimmune diseases.

Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis.

Recent genetic studies have led to identification of numerous loci that are associated with susceptibility to autoimmune diseases. The strategy of using information from these studies has facilitated the identification of novel juvenile idiopathic arthritis (JIA) susceptibility loci, specifically, PTPN22 and IL2RA. Several novel autoimmune susceptibility loci have recently been identified, and we hypothesise that single-nucleotide polymorphisms (SNPs) within these genes may also be JIA susceptibility loci. Five SNPs within the genes AFF3, IL2/IL21, IL7R, CTLA4 and CD226, previously associated with multiple autoimmune diseases were genotyped, in a large data set of Caucasian JIA patients and controls, and tested for association with JIA. We identified two susceptibility loci for JIA, AFF3 and the IL2/IL21 region and additional weak evidence supporting an association with the CTLA4 and IL7R genes, which warrant further investigation. All results require validation in independent JIA data sets. Further characterisation of the specific causal variants will be required before functional studies can be performed.

Association of the CCR5 gene with juvenile idiopathic arthritis.

The CC chemokine receptor 5 (CCR5) has been shown to be important in the recruitment of T-helper cells to the synovium, where they accumulate, drive the inflammatory process and the consequent synovitis and joint destruction. A 32 base-pair insertion/deletion variant (CCR5Δ32) within the gene leads to a frame shift and a nonfunctional receptor. CCR5Δ32 has been investigated for its association with juvenile idiopathic arthritis (JIA), with conflicting results. The aim of this study was to investigate whether CCR5Δ32 is associated with JIA in an UK population. CCR5Δ32 was genotyped in JIA cases (n=1054) and healthy controls (n=3129) and genotype and allele frequencies were compared. A meta-analysis of our study combined with previously published studies was performed. CCR5Δ32 was significantly associated with protection from developing JIA, in this UK data set (P(trend)=0.006, odds ratio (OR) 0.79 95% confidence interval (95% CI): 0.66-0.94). The meta-analysis of all published case-control association studies confirmed the protective association with JIA (P=0.001 OR 0.82 95% CI: 0.73-0.93). CCR5Δ32 is a functional variant determining the number of receptors on the surface of T cells, and it is hypothesized that the level of CCR5 expression could influence the migration of proinflammatory T cells into the synovium and thus susceptibility to JIA.

Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms.

BACKGROUND: The use of methotrexate is limited by interindividual variability in response. Previous studies in patients with either rheumatoid arthritis or psoriasis suggest that genetic variation across the methotrexate metabolic pathway might enable prediction of both efficacy and toxicity of the drug. OBJECTIVES: To assess if single nucleotide polymorphisms (SNPs) across four genes that are relevant to methotrexate metabolism [folypolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR) and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC)] are related to treatment outcomes in patients with psoriasis. METHODS: DNA was collected from 374 patients with psoriasis who had been treated with methotrexate. Data were available on individual outcomes to therapy, namely efficacy and toxicity. Haplotype-tagging SNPs (r(2) > 0.8) for the four genes with a minor allele frequency of > 5% were selected from the HAPMAP phase II data. Genotyping was undertaken using the MassARRAY spectrometric method (Sequenom). RESULTS: There were no significant associations detected between clinical outcomes in patients with psoriasis treated with methotrexate and SNPs in the four genes investigated. CONCLUSIONS: Genetic variation in four key genes relevant to the intracellular metabolism of methotrexate does not appear to predict response to methotrexate therapy in patients with psoriasis.

Development and application of a catchment scale pesticide fate and transport model for use in drinking water risk assessment.

This paper describes the development and application of IMPT (Integrated Model for Pesticide Transport), a parameter-efficient tool for predicting diffuse-source pesticide concentrations in surface waters used for drinking water supply. The model was applied to a small UK headwater catchment with high frequency (8h) pesticide monitoring data and to five larger catchments (479-1653km(2)) with sampling approximately every 14days. Model performance was good for predictions of both flow (Nash Sutcliffe Efficiency generally >0.59 and PBIAS <10%) and pesticide concentrations, although low sampling frequency in the larger catchments is likely to mask the true episodic nature of exposure. The computational efficiency of the model, along with the fact that most of its parameters can be derived from existing national soil property data mean that it can be used to rapidly predict pesticide exposure in multiple surface water resources to support operational and strategic risk assessments.

Detection of drug-resistant HIV-1 strains.

Human immunodeficiency virus (HIV-1) encodes proteins essential to its replication cycle. Reverse transcriptase, protease, and viral envelope gp120 are three proteins that have been targeted for antiviral drug development. Eleven inhibitors of reverse transcriptase, seven inhibitors of protease, and one inhibitor of viral envelope binding have been approved for use. Antiretroviral therapy has reversed the mortality rate of HIV-infected persons, but over time, therapy-resistant virus variants may outgrow. A large body of information is now available to relate specific amino acid sequences in the resistant variants to specific drug regimens. Designing therapy to compensate for virus resistance results in improved patient outcomes. The advent of microsequencing technologies paved the way for direct sequencing of DNA products generated by polymerase chain reactions, thus dramatically lowering the cost of HIV gene sequencing. Designing therapy according to genetic analysis of HIV variants will not only also improve clinical outcome, but will also deter the transmission of drug-resistant strains.

Association of protein kinase C alpha (PRKCA) gene with multiple sclerosis in a UK population.

Twin, family and adoption studies suggest that susceptibility to multiple sclerosis is substantially mediated by genetic factors. Linkage to human chromosome 17q, homologous to a locus linked to experimental animal models of multiple sclerosis, has been widely replicated and the region likely to harbour a multiple sclerosis susceptibility gene has recently been refined to a 2.5 Mb region of 17q22-24. The candidate multiple sclerosis susceptibility gene, protein kinase C alpha (PRKCA), maps within this interval and association with 35 single-nucleotide polymorphism (SNP) markers, spanning the gene with a median spacing of 7.8 kb, was tested using a case-control approach. Single-marker genotype and estimated haplotype frequencies were compared in UK unrelated cases with multiple sclerosis (n = 184) and healthy controls (n = 340) in order to investigate association with susceptibility to disease. A haplotype of two SNPs mapping to the proximal region of the gene showed evidence for association with susceptibility (Bonferroni-corrected P value = 1.1 x 10(-5)). These findings suggest that further investigation of the PRKCA gene is warranted, particularly in cohorts with evidence of linkage to 17q22. Most of the SNPs investigated in this study were intronic and screening to identify disease-associated functional mutations is now required. Our results suggest that the promoter and proximal gene region should be not only included but prioritized in any screening strategy.

Identification of a locus for a form of spondyloepiphyseal dysplasia on chromosome 15q26.1: exclusion of aggrecan as a candidate gene.

We have investigated a family with an autosomal dominant form of spondyloepiphyseal dysplasia (SED) characterised by short stature and severe premature degenerative arthropathy. Previous studies have excluded linkage between this condition and the locus for the type II collagen gene. Here we report the identification of linkage between this disorder and a locus on the long arm of chromosome 15 between markers D15S979 and D15S1004. According to current linkage maps and sequence data, this locus includes that of the aggrecan gene (AGC1). Our linkage data from the SED family show, however, that AGC1 maps to a locus that is proximal to D15S979. This proximal location for AGC1 is further supported by linkage data from a second family with an autosomal recessive form of multiple epiphyseal dysplasia that also maps to the SED locus. In both families AGC1 is therefore excluded as a candidate gene.

The plant cell cycle in context.

Biological scientists are eagerly confronting the challenge of understanding the regulatory mechanisms that control the cell division cycle in eukaryotes. New information will have major implications for the treatment of growth-related diseases and cancer in animals. In plants, cell division has a key role in root and shoot growth as well as in the development of vegetative storage organs and reproductive tissues such as flowers and seeds. Many of the strategies for crop improvement, especially those aimed at increasing yield, involve the manipulation of cell division. This review describes, in some detail, the current status of our understanding of the regulation of cell division in eukaryotes and especially in plants. It also features an outline of some preliminary attempts to exploit transgenesis for manipulation of plant cell division.

Treatment of cutaneous squamous cell carcinomas by intralesional interferon alfa-2b therapy.

BACKGROUND AND DESIGN: Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. RESULTS: Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. CONCLUSIONS: This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result.

An analysis of a general practitioner's workload in a disabled housing development.

Workload in a newly opened disabled housing unit was studied for the years 1989, 1993 and 1995. The impact on one general practitioner was evaluated, and dramatically higher consulting, referral and prescribing rates were demonstrated. The opening of a unit for young disabled people has important implications for the workload of a general practitioner and adequate resources need to be provided.

An investigation of spinal bone mineral density measured laterally: a normal range for UK women.

A UK normal range for 250 volunteers was established for bone mineral density (BMD) of the lumbar spine (L2-L4) measured laterally in the decubitus position. Two software defined regions of interest ("Body" and "Mid") within the vertebral body were analysed throughout. As expected, a negative correlation of BMD with age was found for Body (r = -0.55, p < 0.001) and Mid (r = -0.56, p < 0.001). The age related bone loss from young to old (20-80 years) was 40% in L3 (Body) and 45% in L3 (Mid). In 22% of the cases only L3 could be measured owing to the influence of rib over L2 and interference of the iliac crest over L4. Age related normal ranges (+/- 2 standard deviations) for the three lumbar vertebra L2, L3, L4 for young normals (age 19-39 years) were found to be 0.54 to 1.02, 0.49 to 1.05 and 0.5 to 1.14 g cm-2 respectively for the Body region and 0.49 to 0.97, 0.45 to 1.01 and 0.45 to 1.13 g cm-2 respectively for the Mid region. These ranges can now be used as reference values for patients with suspected osteoporosis and possibly for future fracture prediction. The in vivo precision in 19 volunteers was found to be 4.2% and 5.6% on Body and Mid respectively. The short term (less than 1 week) in vitro precision was 3.1% and 2.7% respectively. From these data it appears that there is a greater measured age related drop in BMD in the vertebral body (measured laterally) than in the entire vertebra (measured anterior-posteriorly) indicating that the lateral measurement may prove to be more sensitive in predicting fracture. The precision of these results indicates that lateral measurements of the spine are not yet useful for monitoring individuals over short term periods and are less useful for studying the effects of drug treatment than the more traditional anterior-posterior measurement of the spine and femur.

Adolescent sexual strategies.

PURPOSE: The aim of this study has been to survey adolescents' strategies to promote sexual encounters and to compare those used by males and females. We examined the predictions that sexual strategies of young adolescents are fewer and less adult-like and that those of male adolescents are more coercive. We also examined the predictions from evolutionary psychology that suggest in sexual strategies, males communicate emotional involvement, long-term interest, and resource investment, whereas females communicate sexual availability and fertility. METHODS: The sample consisted of 153 African-American, white, Chinese-American, and Mexican-American adolescents. A strategy inventory was developed and mention of strategies by males and females were compared. RESULTS: Significant gender differences in mention of strategies were found. Males mentioned a higher percentage of coercive strategies such as pressuring and raping as well as a higher percentage of strategies such as lying and getting a partner drunk or high. Males and females both mentioned a higher percentage of strategies communicating commitment and investment. Females mentioned more strategies which signaled sexual availability. Adolescent strategies were fewer than those reported by adults and less focused on appearance enhancement and the intricacies of dating. CONCLUSIONS: Findings suggest the need for special targeting of coercive situations, use of sexual strategies as a prompt for counterstrategies aimed at abstinence, use of sexual strategies as a context for condom use promotion, and reinforcement of female preparatory strategies.

PIP: 153 sexually active 11th and 12th graders attending two inner-city high schools in San Francisco participated in a study of strategies adolescents use to secure sexual intercourse with a partner. The study sample comprised 20 male and 16 female African-Americans, 21 male and 22 female Caucasians, 17 male and 18 female Chinese-Americans, and 19 male and 20 female Mexican-Americans aged 14-19 years (mean age, 16.96 years). Non-English-speaking and special education students were excluded from study. Relative to females, males reported using a higher degree of pressure, rape, lying, and getting a partner drunk or high to encourage sexual involvement. Both sexes reported suggesting interest in developing commitment and a relationship with the intended sex partner to achieve the goal of intercourse. Females mentioned more strategies than males which signaled sexual availability. Relative to adults, the study participants reported fewer strategies and were less focused upon appearance enhancement and the intricacies of dating.

Types of adolescent sexual relationships and associated perceptions about condom use.

PURPOSE: The purpose of this study was to describe the various types of adolescent sexual relationships and to examine the association between the type of sexual relationship and adolescents' perceptions about the consistency with which other adolescents use condoms. METHODS: Adolescents attending a university-based adolescent medicine clinic completed a self-administered questionnaire. Subjects were asked to rate the importance of six qualities (caring about each other, length of time of relationship, ability to talk about anything, ability to talk about sex and condoms, doing things together, and attraction to partner's looks) for each of four different types of sexual relationships (steady, casual, friends, and "one-night stands"). Subjects were also asked to estimate the frequency with which adolescents use condoms with each type of sexual partner. RESULTS: Questionnaires were completed by 75 sexually experienced adolescents. The mean age of the sample was 16.6 years, and 41.3% were male. All qualities, except attraction to partner's looks, were rated more important for steady partners compared with the other partner types, and more important for sexual relationships with casual partners and friends than for "one-night stands" (p < .001). Sexually experienced subjects believed that condoms are used less frequently with steady partners and more frequently with "one-night stands" (p < .001). CONCLUSIONS: Interventions designed to increase the consistency with which adolescents use condoms should take into account the different types of sexual relationships, each with distinct expectancies about the consistency of condom use.