1,059 research outputs found
Role of micronutrients in HIV infection
More than 60% of the estimated 40 million persons with HIV/AIDS worldwide live in sub-Saharan Africa, where poverty, social insecurity, food shortages and malnutrition are major problems.1 In children under the age of 5 years, who live in developing countries, malnutrition has been associated with 50% of the 10.8 million deaths mainly caused by neonatal disorders, diarrhoea, pneumonia, malaria and HIV/AIDS.2 Likewise micronutrient deficiencies are widespread and are associated with increased morbidity and mortality particularly in relation to infectious diseases.3 This review focuss on the interaction between
micronutrients and HIV/AIDS and discusses recent research findings that may have important public health implications in terms of the case management of persons with HIV/AIDS Southern African Journal of HIV Medicine Vol. 6 (2) 2005: pp. 18-2
Isolated metaphase chromosomes stabilized by DNA-intercalation or polyamine additon:A comparison
Vital signs for children at triage : a multicentre validation of the revised South African Triage Scale (SATS) for children
CITATION: Twomey, M. et al. 2013. Vital signs for children at triage : a multicentre validation of the revised South African Triage Scale (SATS) for children. South African Medical Journal, 103(5):304-308, doi:10.7196/SAMJ.6877.The original publication is available at http://www.samj.org.zaObjective. To validate a revised version of the paediatric South African Triage Scale (SATS) against admission as a reference standard
and compare the sensitivity of triage using: (i) clinical discriminators; (ii) an age-appropriate physiological composite score; and (iii) a
combination of both.
Methods. A prospective cohort study was undertaken validating the revised paediatric SATS against outcome markers of children at six
emergency centres during a 2-month period in 2011. The primary outcome marker was the proportion of children admitted. Validity
indicators including sensitivity (Se), specificity, positive predictive value and negative predictive value (NPV) were used to estimate the
validity. Associated percentages for over-/under-triage were used to further assess practical application of the paediatric SATS.
Results. A total of 2 014 children were included. The percentage of hospital admissions increased with an increase in the level of urgency
from 5% in the non-urgent patients to 73% in the emergency patients. The data demonstrated that sensitivity increased substantially when
using the SATS, which is a combination of clinical discriminators and the Triage Early Warning Score (TEWS) (Se 91.0%, NPV 95.3%),
compared with use of clinical discriminators in isolation (Se 57.1%, NPV 86.3%) or the TEWS in isolation (Se 75.6%, NPV 89.1%).
Conclusion. The results of this study illustrate that the revised paediatric SATS is a safe and robust triage tool.http://www.samj.org.za/index.php/samj/article/view/6877Publisher's versio
Concepts of health and well-being in managers: An organizational study
Global changes and new managerial challenges require new concepts of health and well-being in organizational contexts. In the South African context, health and well-being of managers have gained relevance in organizations and in management sciences. International organizations, in particular, attempt to address the increasing demand for health care and the delivery of health services to their managers. Careful and appropriate health management requires research to evaluate context-specific health concepts and strategies. The purpose and aim of this article is to assess managerial concepts on health and well-being that could be used by the organization to contribute to managerial well-being by implementing health promotion according to managerial needs. At the same time, this article contributes to salutogenetic health research that is very rare with regard to the South African organizational management research
Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)
Background: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. Methods: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. Results: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93–1.04, P=0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89–1.06, P=0.5) mutation carriers. Conclusion: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out. A Osorio1, R L Milne2, G Pita3, P Peterlongo4,5, T Heikkinen6, J Simard7, G Chenevix-Trench8, A B Spurdle8, J Beesley8, X Chen8, S Healey8, KConFab9, S L Neuhausen10, Y C Ding10, F J Couch11,12, X Wang11, N Lindor13, S Manoukian4, M Barile14, A Viel15, L Tizzoni5,16, C I Szabo17, L Foretova18, M Zikan19, K Claes20, M H Greene21, P Mai21, G Rennert22, F Lejbkowicz22, O Barnett-Griness22, I L Andrulis23,24, H Ozcelik24, N Weerasooriya23, OCGN23, A-M Gerdes25, M Thomassen25, D G Cruger26, M A Caligo27, E Friedman28,29, B Kaufman28,29, Y Laitman28, S Cohen28, T Kontorovich28, R Gershoni-Baruch30, E Dagan31,32, H Jernström33, M S Askmalm34, B Arver35, B Malmer36, SWE-BRCA37, S M Domchek38, K L Nathanson38, J Brunet39, T Ramón y Cajal40, D Yannoukakos41, U Hamann42, HEBON37, F B L Hogervorst43, S Verhoef43, EB Gómez García44,45, J T Wijnen46,47, A van den Ouweland48, EMBRACE37, D F Easton49, S Peock49, M Cook49, C T Oliver49, D Frost49, C Luccarini50, D G Evans51, F Lalloo51, R Eeles52, G Pichert53, J Cook54, S Hodgson55, P J Morrison56, F Douglas57, A K Godwin58, GEMO59,60,61, O M Sinilnikova59,60, L Barjhoux59,60, D Stoppa-Lyonnet61, V Moncoutier61, S Giraud59, C Cassini62,63, L Olivier-Faivre62,63, F Révillion64, J-P Peyrat64, D Muller65, J-P Fricker65, H T Lynch66, E M John67, S Buys68, M Daly69, J L Hopper70, M B Terry71, A Miron72, Y Yassin72, D Goldgar73, Breast Cancer Family Registry37, C F Singer74, D Gschwantler-Kaulich74, G Pfeiler74, A-C Spiess74, Thomas v O Hansen75, O T Johannsson76, T Kirchhoff77, K Offit77, K Kosarin77, M Piedmonte78, G C Rodriguez79, K Wakeley80, J F Boggess81, J Basil82, P E Schwartz83, S V Blank84, A E Toland85, M Montagna86, C Casella87, E N Imyanitov88, A Allavena89, R K Schmutzler90, B Versmold90, C Engel91, A Meindl92, N Ditsch93, N Arnold94, D Niederacher95, H Deißler96, B Fiebig97, R Varon-Mateeva98, D Schaefer99, U G Froster100, T Caldes101, M de la Hoya101, L McGuffog49, A C Antoniou49, H Nevanlinna6, P Radice4,5 and J Benítez1,3 on behalf of CIMB
HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.
Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification
Arsenic-related DNA copy-number alterations in lung squamous cell carcinomas
BACKGROUND: Lung squamous cell carcinomas (SqCCs) occur at higher rates following arsenic exposure. Somatic DNA copy-number
alterations (CNAs) are understood to be critical drivers in several tumour types. We have assembled a rare panel of lung tumours
from a population with chronic arsenic exposure, including SqCC tumours from patients with no smoking history.
METHODS: Fifty-two lung SqCCs were analysed by whole-genome tiling-set array comparative genomic hybridisation. Twenty-two
were derived from arsenic-exposed patients from Northern Chile (10 never smokers and 12 smokers). Thirty additional cases were
obtained for comparison from North American smokers without arsenic exposure. Twenty-two blood samples from healthy
individuals from Northern Chile were examined to identify germline DNA copy-number variations (CNVs) that could be excluded
from analysis.
RESULTS: We identified multiple CNAs associated with arsenic exposure. These alterations were not attributable to either smoking
status or CNVs. DNA losses at chromosomes 1q21.1, 7p22.3, 9q12, and 19q13.31 represented the most recurrent events.
An arsenic-associated gain at 19q13.33 contains genes previously identified as oncogene candidates.
CONCLUSIONS: Our results provide a comprehensive approach to molecular characteristics of the arsenic-exposed lung cancer
genome and the non-smoking lung SqCC genome. The distinct and recurrent arsenic-related alterations suggest that this group of
tumours may be considered as a separate disease subclass
A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers
Nat Genet
Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 x 10(-8)). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification
Living in rural New England amplifies the risk of depression in patients with HIV
<p>Abstract</p> <p>Background</p> <p>The importance of depression as a complication of HIV infection is increasingly understood, and people living in rural areas are at increased risk for depression. However, it is not known whether living in rural areas amplifies the risk of depression in patients with HIV.</p> <p>Methods</p> <p>We compared the prevalence of depression between rural and metropolitan HIV patients seen at the Dartmouth-Hitchcock HIV Program in a retrospective cohort study. Using the validated Rural-Urban Commuting Area Score, we categorized patients as living in small town/rural areas, micropolitan or metropolitan towns. Then, using a multivariate logistic regression model to adjust for demographic factors that differed between rural and metropolitan patients, we estimated the impact of living in rural areas on the odds of depression.</p> <p>Results</p> <p>Among 646 patients with HIV (185 small town/rural, 145 micropolitan, 316 metropolitan), rural patients were older, white, male, and men who have sex with men (ANOVA, F-statistic < 0.05). The prevalence of depression was highest in rural patients (59.5 vs. 51.7 vs. 41.2%, F statistic < 0.001), particularly rural patients on antiretroviral therapy (72.4 vs. 53.5 vs. 38.2%, F-statistic < 0.001. A multivariate logistic regression model showed that the odds of depression in rural patients with HIV were 1.34 (P < 0.001).</p> <p>Conclusion</p> <p>HIV-infected patients living in rural areas, particularly those on antiretroviral therapy, are highly vulnerable to depression.</p
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