The potato R locus codes for dihydroflavonol 4-reductase

The potato R locus is required for the production of red pelargonidin-based anthocyanin pigments in potato (Solanum tuberosum L.). Red color also requires tissue-specific regulatory genes, such as D (for expression in tuber skin) and F (expression in flowers). A related locus, P, is required for production of blue/purple anthocyanins; P is epistatic to R. We have previously reported that the dihydroflavonol 4-reductase gene (dfr) co-segregates with R. To test directly whether R corresponds to dfr, we placed the allele of dfr associated with red color under the control of the CaMV 35S promoter and introduced it into the potato cultivar Prince Hairy (genotype dddd rrrr P-), which has white tubers and pale blue flowers. Transgenic Prince Hairy tubers remained white, but flower color changed to purple. Three independent transgenic lines, as well as a vector-transformed line, were then crossed with the red-skinned variety Chieftain (genotype D-R-pppp), to establish populations that segregated for D, R, P, and the dfr transgene or empty vector. Markers were used to genotype progeny at D and R. Progeny carrying the empty vector in the genetic background D-rrrr produced white or purple tubers, while progeny with the same genotype and the dfr transgene produced red or purple tubers. HPLC and LC–MS/MS analyses of anthocyanins present in Chieftain and in a red-skinned progeny clone with the dfr transgene in a D-rrrr background revealed no qualitative differences. Thus, dfr can fully complement R, both in terms of tuber color and anthocyanin composition

Prevalence and factors associated with poor performance in the 5‐chair stand test: findings from the Cognitive Function and Ageing Study II and proposed Newcastle protocol for use in the assessment of sarcopenia

Background Poor performance in the 5‐chair stand test (5‐CST) indicates reduced lower limb muscle strength. The 5‐CST has been recommended for use in the initial assessment of sarcopenia, the accelerated loss of muscle strength and mass. In order to facilitate the use of the 5‐CST in sarcopenia assessment, our aims were to (i) describe the prevalence and factors associated with poor performance in the 5‐CST, (ii) examine the relationship between the 5‐CST and gait speed, and (iii) propose a protocol for using the 5‐CST. Methods The population‐based study Cognitive Function and Ageing Study II recruited people aged 65 years and over from defined geographical localities in Cambridgeshire, Newcastle, and Nottingham. The study collected data for assessment of functional ability during home visits, including the 5‐CST and gait speed. We used multinomial logistic regression to assess the associations between factors including the SARC‐F questionnaire and the category of 5‐CST performance: fast (15 s), or unable, with slow/unable classed as poor performance. We reviewed previous studies on the protocol used to carry out the 5‐CST. Results A total of 7190 participants aged 65+ from the three diverse localities of Cognitive Function and Ageing Study II were included (54.1% female). The proportion of those with poor performance in the 5‐CST increased with age, from 34.3% at age 65–69 to 89.7% at age 90+. Factors independently associated with poor performance included positive responses to the SARC‐F questionnaire, physical inactivity, depression, impaired cognition, and multimorbidity (all P < 0.005). Most people with poor performance also had slow gait speed (57.8%) or were unable to complete the gait speed test (18.4%). We found variation in the 5‐CST protocol used, for example, timing until a participant stood up for the fifth time or until they sat down afterwards. Conclusions Poor performance in the 5‐CST is increasingly common with age and is associated with a cluster of other factors that characterize risk for poor ageing such as physical inactivity, impaired cognition, and multimorbidity. We recommend a low threshold for performing the 5‐CST in clinical settings and provide a protocol for its use

Biomarker-Based HIV Incidence in a Community Sample of Men Who Have Sex with Men in Paris, France

BACKGROUND: Population-based estimates of HIV incidence in France have revealed that men who have sex with men (MSM) are the most affected population and contribute to nearly half of new infections each year. We sought to estimate HIV incidence among sexually active MSM in Paris gay community social venues. METHODOLOGY/ PRINCIPAL FINDINGS: A cross-sectional survey was conducted in 2009 in a sample of commercial venues such as bars, saunas and backrooms. We collected a behavioural questionnaire and blood sample. Specimens were tested for HIV infection and positive specimens then tested for recent infection by the enzyme immunoassay for recent HIV-1 infection (EIA-RI). We assessed the presence of antiretroviral therapy among infected individuals to rule out treated patients in the algorithm that determined recent infection. Biomarker-based cross-sectional incidence estimates were calculated. We enrolled 886 MSM participants among which 157 (18%) tested HIV positive. In positive individuals who knew they were infected, 75% of EIA-RI positive results were due to ART. Of 157 HIV positive specimens, 15 were deemed to be recently infected. The overall HIV incidence was estimated at 3.8% person-years (py) [95%CI: 1.5-6.2]. Although differences were not significant, incidence was estimated to be 3.5% py [0.1-6.1] in men having had a negative HIV test in previous year and 4.8% py [0.1-10.6] in men having had their last HIV test more than one year before the survey, or never tested. Incidence was estimated at 4.1% py [0-8.3] in men under 35 years and 2.5% py [0-5.4] in older men. CONCLUSIONS/ SIGNIFICANCE: This is the first community-based survey to estimate HIV incidence among MSM in France. It includes ART detection and reveals a high level of HIV transmission in sexually active individuals, despite a high uptake of HIV testing. These data call for effective prevention programs targeting MSM engaged in high-risk behaviours

The campaign for a National Strategy for Gypsy site provision and the role of Public Health activism in the 1960–1970s

We trace the post-war evolution of a national approach to providing caravan sites for Gypsies and Travellers—something essential to protect the health of that population in the United Kingdom (UK). Throughout the 1950s and 1960s, the late Norman Dodds MP championed in Parliament the plight of the UK’s Gypsies and other nomads. He was instrumental in galvanising support for the 1968 Caravan Sites Act. The vision of influential individuals working in public and environmental health surmounted practical considerations and local opposition to implement the national programme of site provision envisioned by the Act. We detail this hitherto neglected aspect of Gypsy politics and policy development. In doing so, we highlight the transformative potential of public health and argue for a return to the comprehensive vision motivating these pioneers in the 1960s and 1970s

Developing a matrix to identify and prioritise research recommendations in HIV Prevention

BACKGROUND: HIV prevention continues to be problematic in the UK, as it does globally. The UK Department of Health has a strategic direction with greater focus on prevention as part of its World Class Commissioning Programme. There is a need for targeted evidence-based prevention initiatives. This is an exploratory study to develop an evidence mapping tool in the form of a matrix: this will be used to identify important gaps in contemporary HIV prevention evidence relevant to the UK. It has the potential to aid prioritisation in future research.METHODS: Categories for prevention and risk groups were developed for HIV prevention in consultation with external experts. These were used as axes on a matrix tool to map evidence. Systematic searches for publications on HIV prevention were undertaken using electronic databases for primary and secondary research undertaken mainly in UK, USA, Canada, Australia and New Zealand, 2006-9. Each publication was screened for inclusion then coded. The risk groups and prevention areas in each paper were counted: several publications addressed multiple risk groups. The counts were exported to the matrix and clearly illustrate the concentrations and gaps of literature in HIV prevention.RESULTS: 716 systematic reviews, randomised control trials and other primary research met the inclusion criteria for HIV prevention. The matrix identified several under researched areas in HIV prevention.CONCLUSIONS: This is the first categorisation system for HIV prevention and the matrix is a novel tool for evidence mapping. Some important yet under-researched areas have been identified in HIV prevention evidence: identifying the undiagnosed population; international adaptation; education; intervention combinations; transgender; sex-workers; heterosexuals and older age groups.<br/

Prevalence and correlates of frailty in an older rural African population:findings from the HAALSI cohort study

Background: Frailty is a key predictor of death and dependency, yet little is known about frailty in sub-Saharan Africa despite rapid population ageing. We describe the prevalence and correlates of phenotypic frailty using data from the Health and Aging in Africa: Longitudinal Studies of an INDEPTH Community cohort. Methods: We analysed data from rural South Africans aged 40 and over. We used low grip strength, slow gait speed, low body mass index, and combinations of self-reported exhaustion, decline in health, low physical activity and high self-reported sedentariness to derive nine variants of a phenotypic frailty score. Each frailty category was compared with self-reported health, subjective wellbeing, impairment in activities of daily living and the presence of multimorbidity. Cox regression analyses were used to compare subsequent all-cause mortality for non-frail (score 0), pre-frail (score 1–2) and frail participants (score 3+). Results: Five thousand fifty nine individuals (mean age 61.7 years, 2714 female) were included in the analyses. The nine frailty score variants yielded a range of frailty prevalences (5.4% to 13.2%). For all variants, rates were higher in women than in men, and rose steeply with age. Frailty was associated with worse subjective wellbeing, and worse self-reported health. Both prefrailty and frailty were associated with a higher risk of death during a mean 17 month follow up for all score variants (hazard ratios 1.29 to 2.41 for pre-frail vs non-frail; hazard ratios 2.65 to 8.91 for frail vs non-frail). Conclusions: Phenotypic frailty could be measured in this older South African population, and was associated with worse health, wellbeing and earlier death

Development of a UK core dataset for geriatric medicine research: a position statement and results from a Delphi consensus process

BACKGROUND: There is lack of standardisation in assessment tools used in geriatric medicine research, which makes pooling of data and cross-study comparisons difficult. METHODS: We conducted a modified Delphi process to establish measures to be included within core and extended datasets for geriatric medicine research in the United Kingdom (UK). This included three complete questionnaire rounds, and one consensus meeting. Participants were selected from attendance at the NIHR Newcastle Biomedical Research Centre meeting, May 2019, and academic geriatric medicine e-mailing lists. Literature review was used to develop the initial questionnaire, with all responses then included in the second questionnaire. The third questionnaire used refined options from the second questionnaire with response ranking. RESULTS: Ninety-eight responses were obtained across all questionnaire rounds (Initial: 19, Second: 21, Third: 58) from experienced and early career researchers in geriatric medicine. The initial questionnaire included 18 questions with short text responses, including one question for responders to suggest additional items. Twenty-six questions were included in the second questionnaire, with 108 within category options. The third questionnaire included three ranking, seven final agreement, and four binary option questions. Results were discussed at the consensus meeting. In our position statement, the final consensus dataset includes six core domains: demographics (age, gender, ethnicity, socioeconomic status), specified morbidities, functional ability (Barthel and/or Nottingham Extended Activities of Daily Living), Clinical Frailty Scale (CFS), cognition, and patient-reported outcome measures (dependent on research question). We also propose how additional variables should be measured within an extended dataset. CONCLUSIONS: Our core and extended datasets represent current consensus opinion of academic geriatric medicine clinicians across the UK. We consider the development and further use of these datasets will strengthen collaboration between researchers and academic institutions

Process skill rather than motor skill seems to be a predictor of costs for rehabilitation after a stroke in working age; a longitudinal study with a 1 year follow up post discharge

<p>Abstract</p> <p>Background</p> <p>In recent years a number of costs of stroke studies have been conducted based on incidence or prevalence and estimating costs at a given time. As there still is a need for a deeper understanding of factors influencing these costs the aim of this study was to calculate the direct and indirect costs in a younger (<65) sample of stroke patients and to explore factors affecting the costs.</p> <p>Methods</p> <p>Fifty-eight patients included in a study of home rehabilitation and followed for 1 year after discharge from the rehabilitation unit, were interviewed about their use of health care services, assistance, medications and assistive devices. Costs (defined as the cost for society) were calculated. A linear regression of cost and variables of functioning, ability, community integration and health-related quality of life was done.</p> <p>Results</p> <p>Inpatient care contributed substantially to the direct cost with a mean length of stay of 92 days. Rehabilitation during the first year constituted of an average of 28 days in day clinics, 38 physiotherapy sessions and 20 occupational therapy sessions. The total direct mean cost was 80 020 € and the indirect cost 35 129 €. The direct costs were influenced by the process skill (the ability to plan and perform a given task and to adapt when needed) and presence of aphasia. Indirect costs for informal care giving increased for patients with a lower health-related quality of life as well as a low score on home integration.</p> <p>Conclusion</p> <p>Costs are high in this group of young (< 65 years) stroke patients compared to other studies, partly due to the length of the stay and partly to loss of productivity.</p

The potato developer (D) locus encodes an R2R3 MYB transcription factor that regulates expression of multiple anthocyanin structural genes in tuber skin

A dominant allele at the D locus (also known as I in diploid potato) is required for the synthesis of red and purple anthocyanin pigments in tuber skin. It has previously been reported that D maps to a region of chromosome 10 that harbors one or more homologs of Petuniaan2, an R2R3 MYB transcription factor that coordinately regulates the expression of multiple anthocyanin biosynthetic genes in the floral limb. To test whether D acts similarly in tuber skin, RT-PCR was used to evaluate the expression of flavanone 3-hydroxylase (f3h), dihydroflavonol 4-reductase (dfr) and flavonoid 3′,5′-hydroxylase (f3′5′h). All three genes were expressed in the periderm of red- and purple-skinned clones, while dfr and f3′5′h were not expressed, and f3h was only weakly expressed, in white-skinned clones. A potato cDNA clone with similarity to an2 was isolated from an expression library prepared from red tuber skin, and an assay developed to distinguish the two alleles of this gene in a diploid potato clone known to be heterozygous Dd. One allele was observed to cosegregate with pigmented skin in an F1 population of 136 individuals. This allele was expressed in tuber skin of red- and purple-colored progeny, but not in white tubers, while other parental alleles were not expressed in white or colored tubers. The allele was placed under the control of a doubled 35S promoter and transformed into the light red-colored cultivar Désirée, the white-skinned cultivar Bintje, and two white diploid clones known to lack the functional allele of D. Transformants accumulated pigment in tuber skin, as well as in other tissues, including young foliage, flower petals, and tuber flesh