New Marker of Colon Cancer Risk Associated with Heme Intake: 1,4-Dihydroxynonane Mercapturic Acid

Background: Red meat consumption is associated with an increased risk of colon cancer. Animal studies show that heme, found in red meat, promotes preneoplastic lesions in the colon, probably due to the oxidative properties of this compound. End products of lipid peroxidation, such as 4-hydroxynonenal metabolites or 8-iso-prostaglandin-F2 (8-iso-PGF2), could reflect this oxidative process and could be used as biomarkers of colon cancer risk associated with heme intake. Methods: We measured urinary excretion of 8-iso-PGF2 and 1,4-dihydroxynonane mercapturic acid (DHN-MA), the major urinary metabolite of 4-hydroxynonenal, in three studies. In a short-term and a carcinogenesis long-term animal study, we fed rats four different diets (control, chicken, beef, and blood sausage as a high heme diet). In a randomized crossover human study, four different diets were fed (a 60 g/d red meat baseline diet, 120 g/d red meat, baseline diet supplemented with heme iron, and baseline diet supplemented with non-heme iron). Results: DHN-MA excretion increased dramatically in rats fed high heme diets, and the excretion paralleled the number of preneoplastic lesions in azoxymethane initiated rats (P < 0.0001). In the human study, the heme supplemented diet resulted in a 2-fold increase in DHN-MA (P < 0.001). Urinary 8-iso-PGF2 increased moderately in rats fed a high heme diet (P < 0.0001), but not in humans. Conclusion: Urinary DHN-MA is a useful noninvasive biomarker for determining the risk of preneoplastic lesions associated with heme iron consumption and should be further investigated as a potential biomarker of colon cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2274–9

Freeze-Dried Ham Promotes Azoxymethane-Induced Mucin-Depleted Foci and Aberrant Crypt Foci in Rat Colon

Processed and red meat consumption is associated with the risk of colorectal cancer. Meta-analyses have suggested that the risk associated with processed meat is higher. Most processed meats are cured and cooked, which leads to formation of free nitrosyl heme. We speculated that free nitrosyl heme is more toxic than native myoglobin. The promoting effect of a freeze-dried, cooked, cured ham diet was looked for in a 100-day study. Colon carcinogenesis endpoints were aberrant crypt foci and mucin depleted foci (MDF). A second study (14 days) was designed 1) to compare the effect of ham, hemoglobin, and hemin; and 2) to test the effect of sodium chloride, nitrite, and phosphate in diet on early biomarkers associated with heme-induced promotion. In the 100-day study, control and ham-fed rats had 3.5 and 8.5 MDF/colon, respectively (P < 0.0001). Promotion was associated with cytotoxicity and lipid peroxidation. In the short-term study, cytotoxicity and lipid peroxidation of fecal water, and the urinary marker of lipid peroxidation, increased dramatically in ham- and hemin-fed rat. In contrast, the hemoglobin diet, sodium chloride, nitrite, phosphate diet had no effect. Freeze-dried cooked ham can promote colon carcinogenesis in a rodent model. Hemin, but not hemoglobin, mimicked ham effect on early biochemical markers associated with carcinogenesis

An assessment of implementation of community - oriented primary care in Kenyan family medicine postgraduate medical education programmes

Background and objectives: Family medicine postgraduate programmes in Kenya are examining the benefits of Community-Oriented Primary Care (COPC) curriculum, as a method to train residents in population-based approaches to health care delivery. Whilst COPC is an established part of family medicine training in the United States, little is known about its application in Kenya. We sought to conduct a qualitative study to explore the development and implementation of COPC curriculum in the first two family medicine postgraduate programmes in Kenya. Method: Semi-structured interviews of COPC educators, practitioners, and academic stakeholders and focus groups of postgraduate students were conducted with COPC educators, practitioners and academic stakeholders in two family medicine postgraduate programmes in Kenya. Discussions were transcribed, inductively coded and thematically analysed. Results: Two focus groups with eight family medicine postgraduate students and interviews with five faculty members at two universities were conducted. Two broad themes emerged from the analysis: expected learning outcomes and important community-based enablers. Three learning outcomes were (1) making a community diagnosis, (2) understanding social determinants of health and (3) training in participatory research. Three community-based enablers for sustainability of COPC were (1) partnerships with community health workers, (2) community empowerment and engagement and (3) institutional financial support. Conclusions: Our findings illustrate the expected learning outcomes and important communitybased enablers associated with the successful implementation of COPC projects in Kenya and will help to inform future curriculum development in Kenya

Cooking fish and drinking milk? Patterns in pottery use in the southeastern Baltic, 3300–2400 cal BC

yesA study of pottery vessel contents and use was undertaken in order to obtain information on food processed in Subneolithic and Neolithic vessels from Nida and Šventoji (3300–2400 cal BC). The aim is to assess pottery use during major changes in the coastal environment and in material culture. Bulk carbon and nitrogen isotope, lipid biomarker and compound specific carbon isotope analysis was undertaken on ‘foodcrusts’, charred deposits adhering to vessel surfaces, and absorbed residues from different vessel types. In addition, three archaeological seal bones were analysed for bulk collagen and compound specific carbon isotope analysis to establish collagen-lipid offsets to inform interpretation of the data. The results show that the majority of the vessels were used for processing aquatic products. At Nida the data suggest exploitation of freshwater resources and, in the later stages of occupation, dairying. Analysis of a small number of Subneolithic vessels from Šventoji produced results that are also consistent with processing of aquatic products. Other substances identified include Pinaceae sp. resin or tar and beeswax. These data demonstrate that identifying patterns in pottery use contributes to understanding Neolithisation processes

Dose-Specific Adverse Drug Reaction Identification in Electronic Patient Records: Temporal Data Mining in an Inpatient Psychiatric Population

BACKGROUND: Data collected for medical, filing and administrative purposes in electronic patient records (EPRs) represent a rich source of individualised clinical data, which has great potential for improved detection of patients experiencing adverse drug reactions (ADRs), across all approved drugs and across all indication areas. OBJECTIVES: The aim of this study was to take advantage of techniques for temporal data mining of EPRs in order to detect ADRs in a patient- and dose-specific manner. METHODS: We used a psychiatric hospital’s EPR system to investigate undesired drug effects. Within one workflow the method identified patient-specific adverse events (AEs) and links these to specific drugs and dosages in a temporal manner, based on integration of text mining results and structured data. The structured data contained precise information on drug identity, dosage and strength. RESULTS: When applying the method to the 3,394 patients in the cohort, we identified AEs linked with a drug in 2,402 patients (70.8 %). Of the 43,528 patient-specific drug substances prescribed, 14,736 (33.9 %) were linked with AEs. From these links we identified multiple ADRs (p < 0.05) and found them to occur at similar frequencies, as stated by the manufacturer and in the literature. We showed that drugs displaying similar ADR profiles share targets, and we compared submitted spontaneous AE reports with our findings. For nine of the ten most prescribed antipsychotics in the patient population, larger doses were prescribed to sedated patients than non-sedated patients; five patients exhibited a significant difference (p < 0.05). Finally, we present two cases (p < 0.05) identified by the workflow. The method identified the potentially fatal AE QT prolongation caused by methadone, and a non-described likely ADR between levomepromazine and nightmares found among the hundreds of identified novel links between drugs and AEs (p < 0.05). CONCLUSIONS: The developed method can be used to extract dose-dependent ADR information from already collected EPR data. Large-scale AE extraction from EPRs may complement or even replace current drug safety monitoring methods in the future, reducing or eliminating manual reporting and enabling much faster ADR detection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40264-014-0145-z) contains supplementary material, which is available to authorised users

Caracterización de hábitos de higiene y ambientes en lugares de atención integral a población infantil

RESUMEN Objetivo: Identificar hábitos de higiene de niños y cuidadores para la prevención y el control de enfermedades infecciosas en lugares de atención en Bogotá, Colombia; asimismo, caracterizar las bacterias en las superficies de estos ambientes. Método: Se diseñaron, validaron y aplicaron dos instrumentos para evaluar hábitos saludables y se tomaron muestras de superficies en cocinas, baños, salones, colchonetas y juguetes de 230 lugares. Las bacterias aisladas fueron clasificadas por metodologías automatizadas. Resultados: Se aislaron 699 bacterias, donde el mayor porcentaje de crecimiento fue en cocinas (36%). Estos resultados contrastan con lo observado, donde se evidenció que la mayoría de las cocinas se encontraron limpias (80%). La encuesta reportó que 93% de los cuidadores reconocen lavarse las manos antes de manipular alimentos y 23% informó utilizar elementos de protección para la manipulación de alimentos. Conclusión: Se evidencia la necesidad de acompañar e intervenir los hábitos de higiene y de cuidado del ambiente en lugares de atención a población infantil