Identification of sex hormone-binding globulin in the human hypothalamus

Gonadal steroids are known to influence hypothalamic functions through both genomic and non-genomic pathways. Sex hormone-binding globulin ( SHBG) may act by a non-genomic mechanism independent of classical steroid receptors. Here we describe the immunocytochemical mapping of SHBG-containing neurons and nerve fibers in the human hypothalamus and infundibulum. Mass spectrometry and Western blot analysis were also used to characterize the biochemical characteristics of SHBG in the hypothalamus and cerebrospinal fluid (CSF) of humans. SHBG-immunoreactive neurons were observed in the supraoptic nucleus, the suprachiasmatic nucleus, the bed nucleus of the stria terminalis, paraventricular nucleus, arcuate nucleus, the perifornical region and the medial preoptic area in human brains. There were SHBG-immunoreactive axons in the median eminence and the infundibulum. A partial colocalization with oxytocin could be observed in the posterior pituitary lobe in consecutive semithin sections. We also found strong immunoreactivity for SHBG in epithelial cells of the choroid plexus and in a portion of the ependymal cells lining the third ventricle. Mass spectrometry showed that affinity-purified SHBG from the hypothalamus and choroid plexus is structurally similar to the SHBG identified in the CSF. The multiple localizations of SHBG suggest neurohypophyseal and neuroendocrine functions. The biochemical data suggest that CSF SHBG is of brain rather than blood origin. Copyright (c) 2005 S. Karger AG, Base

Estimation of Dietary Iron Bioavailability from Food Iron Intake and Iron Status

Currently there are no satisfactory methods for estimating dietary iron absorption (bioavailability) at a population level, but this is essential for deriving dietary reference values using the factorial approach. The aim of this work was to develop a novel approach for estimating dietary iron absorption using a population sample from a sub-section of the UK National Diet and Nutrition Survey (NDNS). Data were analyzed in 873 subjects from the 2000–2001 adult cohort of the NDNS, for whom both dietary intake data and hematological measures (hemoglobin and serum ferritin (SF) concentrations) were available. There were 495 men aged 19–64 y (mean age 42.7±12.1 y) and 378 pre-menopausal women (mean age 35.7±8.2 y). Individual dietary iron requirements were estimated using the Institute of Medicine calculations. A full probability approach was then applied to estimate the prevalence of dietary intakes that were insufficient to meet the needs of the men and women separately, based on their estimated daily iron intake and a series of absorption values ranging from 1–40%. The prevalence of SF concentrations below selected cut-off values (indicating that absorption was not high enough to maintain iron stores) was derived from individual SF concentrations. An estimate of dietary iron absorption required to maintain specified SF values was then calculated by matching the observed prevalence of insufficiency with the prevalence predicted for the series of absorption estimates. Mean daily dietary iron intakes were 13.5 mg for men and 9.8 mg for women. Mean calculated dietary absorption was 8% in men (50th percentile for SF 85 µg/L) and 17% in women (50th percentile for SF 38 µg/L). At a ferritin level of 45 µg/L estimated absorption was similar in men (14%) and women (13%). This new method can be used to calculate dietary iron absorption at a population level using data describing total iron intake and SF concentration

Why Behavioral And Environmental Interventions Are Needed To Improve Health At Lower Cost

http://dx.doi.org/10.1377/hlthaff.2010.111

Alginate inhibits iron absorption from ferrous gluconate in a randomized controlled trial and reduces iron uptake into Caco-2 cells

Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n=15) were given a test meal of 200g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p=0.003). Sub-group B (n=9) consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p=0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p=0.009). In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p=0.009) and 35% (p=0.003) respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (p<0.001) of that observed with ferrous gluconate alone. The results of these studies demonstrate that alginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification

Comparison of algorithms that detect drug side effects using electronic healthcare databases

The electronic healthcare databases are starting to become more readily available and are thought to have excellent potential for generating adverse drug reaction signals. The Health Improvement Network (THIN) database is an electronic healthcare database containing medical information on over 11 million patients that has excellent potential for detecting ADRs. In this paper we apply four existing electronic healthcare database signal detecting algorithms (MUTARA, HUNT, Temporal Pattern Discovery and modified ROR) on the THIN database for a selection of drugs from six chosen drug families. This is the first comparison of ADR signalling algorithms that includes MUTARA and HUNT and enabled us to set a benchmark for the adverse drug reaction signalling ability of the THIN database. The drugs were selectively chosen to enable a comparison with previous work and for variety. It was found that no algorithm was generally superior and the algorithms’ natural thresholds act at variable stringencies. Furthermore, none of the algorithms perform well at detecting rare ADRs

Determinants of immigration strategies in male crested macaques (Macaca nigra).

Immigration into a new group can produce substantial costs due to resistance from residents, but also reproductive benefits. Whether or not individuals base their immigration strategy on prospective costbenefit ratios remains unknown. We investigated individual immigration decisions in crested macaques, a primate species with a high reproductive skew in favour of high-ranking males. We found two different strategies. Males who achieved low rank in the new group usually immigrated after another male had immigrated within the previous 25 days and achieved high rank. They never got injured but also had low prospective reproductive success. We assume that these males benefitted from immigrating into a destabilized male hierarchy. Males who achieved high rank in the new group usually immigrated independent of previous immigrations. They recieved injuries more frequently and therefore bore immigration costs. They, however, also had higher reproductive success prospects. We conclude that male crested macaques base their immigration strategy on relative fighting ability and thus potential rank in the new group i.e. potential reproductive benefits, as well as potential costs of injury

A qualitative study of health care professionals' views and experiences of paediatric advance care planning

Background Good end-of-life care planning is vital to ensure optimal care is provided for patients and their families. Two key factors are open and honest advance care planning conversations between the patient (where possible), family, and health care professionals, focusing on exploring what their future wishes are; and the development of an advance care plan document. However, in paediatric and neonatal settings, there has been little research to demonstrate how advance care planning conversations take place. This study explored health care professionals’ views and experiences of paediatric advance care planning in hospitals, community settings and hospices. MethodsA qualitative methodology was employed using purposive sampling of health care professionals involved in the end-of-life care for children aged 0–18 years known to the hospital palliative care team, and had died at least three months before, but less than 18 months prior to the study. Ethics committee approval was obtained for the study. Located in the North of England, the study involved three hospitals, a children’s hospice, and community services. Data were collected using semi-structured, digitally recorded, telephone interviews. All interviews were transcribed verbatim and subjected to thematic analysis. ResultsTwenty-one health care professionals participated, including generalist paediatric staff as well as specialist palliative care staff.Two themes were generated from the study: The timing of planning conversations, including waiting for the relationship with the family to form; the introduction of parallel planning; avoiding a crisis situation. Secondly, supporting effective conversations around advance care planning, including where to have the conversation; introducing the conversation; and how to approach the topic encompassing the value of advance care planning and documentation for families. Conclusion The timing of when to start the advance care planning conversations remains an issue for health care professionals. The value of doing it in stages and considering the environment where the conversations are held was noted. Timely planning was seen as vital to avoid difficult conversations at a crisis point and for co-ordination of care. Good advance care planning is to provide the best person-centred care for the child and experience for the family

Second primary cancers after radiation for prostate cancer: a review of data from planning studies

A review of planning studies was undertaken to evaluate estimated risks of radiation induced second primary cancers (RISPC) associated with different prostate radiotherapy techniques for localised prostate cancer. A total of 83 publications were identified which employed a variety of methods to estimate RISPC risk. Of these, the 16 planning studies which specifically addressed absolute or relative second cancer risk using dose–response models were selected for inclusion within this review. There are uncertainties and limitations related to all the different methods for estimating RISPC risk. Whether or not dose models include the effects of the primary radiation beam, as well as out-of-field regions, influences estimated risks. Regarding the impact of IMRT compared to 3D-CRT, at equivalent energies, several studies suggest an increase in risk related to increased leakage contributing to out-of-field RISPC risk, although in absolute terms this increase in risk may be very small. IMRT also results in increased low dose normal tissue irradiation, but the extent to which this has been estimated to contribute to RISPC risk is variable, and may also be very small. IMRT is often delivered using 6MV photons while conventional radiotherapy often requires higher energies to achieve adequate tissue penetration, and so comparisons between IMRT and older techniques should not be restricted to equivalent energies. Proton and brachytherapy planning studies suggest very low RISPC risks associated with these techniques. Until there is sufficient clinical evidence regarding RISPC risks associated with modern irradiation techniques, the data produced from planning studies is relevant when considering which patients to irradiate, and which technique to employ

Higher incidence of premenopausal breast cancer in less developed countries; myth or truth?

Background: Fundamental etiologic differences have been suggested to cause earlier onset of breast cancer in less developed countries (LDCs) than in more developed countries (MDCs). We explored this hypothesis using world-wide breast cancer incidence data. Methods: We compared international age-standardized incidence rates (ASR) of pre- (<50 years) and postmenopausal (≥50 years) breast cancers as well as temporal trends in ASRs of pre-and postmenopausal breast cancer among selected countries during 1975–2008. We used joinpoint log-linear regression analysis to estimate annual percent changes (APC) for premenopausal and postmenopausal breast cancer in the northern Europe and in Black and White women population in the US. Results: Premenopausal breast cancers comprised a substantially higher proportion of all incident breast cancers in LDCs (average 47.3%) compared to MDCs (average 18.5%). However, the ASR of premenopausal breast cancer was consistently higher in MDCs (29.4/100,000) than LDCs (12.8/100,000). The ASR of postmenopausal cancer was about five-fold higher in the MDCs (307.6/100,000) than the LDCs (65.4/100,000). The APC of breast cancer in Denmark was substantially higher in postmenopausal (1.33%) than premenopausal cancer (0.98%). Higher incidence of breast cancer among the white than black women in the US was pertained only to the postmenopausal cancer. Conclusion: The substantial and consistent lower age-specific incidence of breast cancer in LDCs than in MDCs contradicts the theory of earlier onset. Demographic differences with fewer old women in LDCs and lower prevalence of risk factors of postmenopausal cancer are the most likely explanation to the lower mean age at diagnosis in these countries

Diagnostic and economic evaluation of new biomarkers for Alzheimer's disease: the research protocol of a prospective cohort study

Doc number: 72 Abstract Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model. Methods/design: In a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered. Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period. A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers. Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems. Trial registration: NCT0145089