Sex hormone binding globulin and insulin resistance

Sex hormone binding globulin (SHBG) is a glycoprotein composed of two 373-amino-acid subunits. The SHBG gene and a promotor region have been identified. The SHBG receptor has yet to be cloned but is known to act through a G-protein-linked second-messenger system following plasma membrane binding. The principal function of SHBG has traditionally been considered to be that of a transport protein for sex steroids, regulating circulating concentrations of free (unbound) hormones and their transport to target tissues. Recent research suggests that SHBG has functions in addition to the binding and transport of sex steroids. Observational studies have associated a low SHBG concentration with an increased incidence of type 2 diabetes mellitus (DM) independent of sex hormone levels in men and women. Genetic studies using Mendelian randomization analysis linking three single nucleotide polymorphisms of the SHBG gene to risk of developing type 2 DM suggest SHBG may have a role in the pathogenesis of type 2 DM. The correlation between SHBG and insulin resistance that is evident in a number of cross-sectional studies is in keeping with the suggestion that the association between SHBG and incidence of type 2 DM is explained by insulin resistance. Several potential mechanisms may account for this association, including the identification of dietary factors that influence SHBG gene transcription. Further research to characterize the SHBG-receptor and the SHBG second messenger system is required. An interventional study examining the effects on insulin resistance of altering SHBG concentrations may help in determining whether this association is causal.

The development of the PROMPT (PRescribing Optimally in Middle-aged People’s Treatments) criteria

BACKGROUND: Whilst multimorbidity is more prevalent with increasing age, approximately 30% of middle-aged adults (45-64 years) are also affected. Several prescribing criteria have been developed to optimise medication use in older people (≥65 years) with little focus on potentially inappropriate prescribing (PIP) in middle-aged adults. We have developed a set of explicit prescribing criteria called PROMPT (PRescribing Optimally in Middle-aged People's Treatments) which may be applied to prescribing datasets to determine the prevalence of PIP in this age-group.

METHODS: A literature search was conducted to identify published prescribing criteria for all age groups, with the Project Steering Group (convened for this study) adding further criteria for consideration, all of which were reviewed for relevance to middle-aged adults. These criteria underwent a two-round Delphi process, using an expert panel consisting of general practitioners, pharmacists and clinical pharmacologists from the United Kingdom and Republic of Ireland. Using web-based questionnaires, 17 panellists were asked to indicate their level of agreement with each criterion via a 5-point Likert scale (1 = Strongly Disagree, 5 = Strongly Agree) to assess the applicability to middle-aged adults in the absence of clinical information. Criteria were accepted/rejected/revised dependent on the panel's level of agreement using the median response/interquartile range and additional comments.

RESULTS: Thirty-four criteria were rated in the first round of this exercise and consensus was achieved on 17 criteria which were accepted into the PROMPT criteria. Consensus was not reached on the remaining 17, and six criteria were removed following a review of the additional comments. The second round of this exercise focused on the remaining 11 criteria, some of which were revised following the first exercise. Five criteria were accepted from the second round, providing a final list of 22 criteria [gastro-intestinal system (n = 3), cardiovascular system (n = 4), respiratory system (n = 4), central nervous system (n = 6), infections (n = 1), endocrine system (n = 1), musculoskeletal system (n = 2), duplicates (n = 1)].

CONCLUSIONS: PROMPT is the first set of prescribing criteria developed for use in middle-aged adults. The utility of these criteria will be tested in future studies using prescribing datasets.

Temperature dependence of the mid-infrared dielectric function of YBCO in the ab plane

We have excited mid-infrared surface plasmons in two YBCO thin films of contrasting properties using attenuated total reflection of light and found that the imaginary part of the dielectric function decreases linearly with reduction in temperature. This result is in contrast with the commonly reported conclusion of infrared normal reflectance studies. If sustained it may clarify the problem of understanding the normal state properties of YBCO and the other cuprates. The dielectric function of the films, epsilon = epsilon(1) + i epsilon(2), was determined between room temperature and 80K: epsilon(1) was found to be only slightly temperature dependent but somewhat sample dependent, probably as a result of surface and grain boundary contamination. The imaginary part, epsilon(2), (and the real part of the conductivity, sigma(1),) decreased linearly with reduction in temperature in both films. Results obtained were: for film 1: epsilon(1) = - 14.05 - 0.0024T and epsilon(2) - 4.11 + 0.086T and for film 2: epsilon(1) = - 24.09 + 0.0013T and epsilon(2) = 7.66 + 0.067T where T is the temperature in Kelvin. An understanding of the results is offered in terms of temperature-dependent intrinsic intragrain inelastic scattering and temperature-independent contributions: elastic and inelastic grain boundary scattering and optical interband (or localised charge) absorption. The relative contribution of each is estimated. A key conclusion is that the interband (or localised charge) absorption is only similar to 10%. Most importantly, the intrinsic scattering rate, 1/tau, decreases linearly with fall in temperature, T, in a regime where current theory predicts dependence on frequency, omega, to dominate. The coupling constant, lambda, between the charge carriers and the thermal excitations has a value of 1.7, some fivefold greater than the far infrared value. These results imply a need to restate the phenomenology of the normal state of high temperature superconductors and seek a corresponding theoretical understanding.

DC resistance and dielectric function at 3392 nm of YBCO films from 300 K to 80 K

The dielectric function of a YBCO film was determined at 3392nm at temperatures down to 80K. Results obtained were epsilon(i) = -24.09 - 0.0013T and epsilon(i) = 7.66 + 0.067T. The results for epsilon(i) are compared with the de resistance of the film. Intrinsic intragrain scattering, elastic and inelastic grain boundary scattering and optical interband absorption are estimated as 82%, 5%, 13% and 10% respecively at 0K.

Phylogeny and ancient DNA of Sus provides insights into neolithic expansion in Island Southeast Asia and Oceania

Human settlement of Oceania marked the culmination of a global colonization process that began when humans first left Africa at least 90,000 years ago. The precise origins and dispersal routes of the Austronesian peoples and the associated Lapita culture remain contentious, and numerous disparate models of dispersal (based primarily on linguistic, genetic, and archeological data) have been proposed. Here, through the use of mtDNA from 781 modern and ancient Sus specimens, we provide evidence for an early human-mediated translocation of the Sulawesi warty pig (Sus celebensis) to Flores and Timor and two later separate human-mediated dispersals of domestic pig (Sus scrofa) through Island Southeast Asia into Oceania. Of the later dispersal routes, one is unequivocally associated with the Neolithic (Lapita) and later Polynesian migrations and links modern and archeological Javan, Sumatran, Wallacean, and Oceanic pigs with mainland Southeast Asian S. scrofa. Archeological and genetic evidence shows these pigs were certainly introduced to islands east of the Wallace Line, including New Guinea, and that so-called "wild" pigs within this region are most likely feral descendants of domestic pigs introduced by early agriculturalists. The other later pig dispersal links mainland East Asian pigs to western Micronesia, Taiwan, and the Philippines. These results provide important data with which to test current models for human dispersal in the region. © 2007 by The National Academy of Sciences of the USA.