Toward a new prognostic-therapeutic index in geriatric oncology

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Osteoporosis and diabetes

Diabetes mellitus and osteoporosis are chronic diseases with an elevated and growing incidence in the elderly. Recent epidemiological studies have demonstrated an elevated risk of hip, humerus and foot fractures in elder diabetic subjects. While type 1 diabetes is generally associated with a mild reduction in bone mineral density (BMD), type 2 diabetes, more prevalent in old subjects, is frequently linked to a normal or high BMD. Studies on experimental models of diabetes have suggested an altered bone structure that may help to explain the elevated risk of fractures observed in these animals and may as well help to explain the paradox of an incremented risk of fractures in type 2 diabetic elderly in the presence of normal or elevated BMD. In addition, diabetic elderly have an increased risk of falls, consequent at least in part to a poor vision, peripheral neuropathy, and weaken muscular performance. Diabetes may affect bone tissue by different mechanisms including obesity, hyperinsulinemia, deposit of advanced glycosilation end products in collagen fibre, reduced circulating levels of IGF-1, hypercalciuria, renal function impairment, microangiopathy and chronic inflammation. A better understanding of these mechanisms may help implement the prevention of fractures in the growing population of mature diabetics

Should we recommend reductions in saturated fat intake or in red/processed meat consumption? The SUN prospective cohort study

Background & aims: While most studies have shown increased mortality associated with excessive red/processed meat consumption, the association of saturated fatty acids (SFA) intake with mortality is less homogeneous. We aimed to prospectively assess the association of both, meat consumption (red, processed, red + processed, and total) and SFA intake, with the risk of all-cause death. Methods: We assessed 18,540 participants of the SUN (Seguimiento Universidad de Navarra) cohort, followed-up for a mean of 9.5 years. A validated 136-item FFQ was administered at baseline. We used Cox models adjusted for potential confounders. Results: We observed 255 deaths during 176,916 person-years of follow-up. Age modified the association between meat consumption and all-cause mortality (p for interaction = 0.027, 0.075, and 0.013, for red, total, and processed meat, respectively). Among participants aged >45 years the fully-adjusted HRs (95% CIs) for one additional serving/d of red, total, and red + processed meat consumption were 1.47 (1.06, 2.04), 1.23 (1.05, 1.45), and 1.32 (1.05, 1.65), respectively, with significant linear trends (P for trend 0.022, 0.012, and 0.018, respectively). In these participants, SFA intake was non-significantly associated with mortality. However, isocaloric replacement of monounsaturated fat or carbohydrates by SFA resulted in significantly higher mortality risk. Likewise, replacing 100 g of vegetables, fruits & nuts or cereals by 100 g of red meat resulted in higher mortality risk. No association of meat consumption or SFA with all-cause mortality was observed in participants younger than 46 years. Conclusions: Among highly educated persons, aged >45 years, a high consumption of red, total, and red + processed meat was related to increased all-cause mortality, compared with those with low consumption, whereas no significant associations were found for SFA intake. Dietary guidelines should specifically limit meat consumption and not relying only in limiting SFA intake

The Semileptonic Decays D→π(ρ)eνD\to \pi(\rho) e \nu and B→π(ρ)eνB\to \pi (\rho) e \nu from QCD Sum Rules

We investigate the semileptonic decays of B and D mesons into $\pi$ and $\rho$ mesons, respectively, by means of QCD sum rules. We find that for the vector formfactors involved the pole dominance hypothesis is valid to good accuracy with pole masses in the expected range. Pole dominance, however, does not apply to the axial formfactors which results in specific predictions for the predominant polarization of the $\rho$ meson and the shape of the lepton spectrum. For the total decay rates we find $\Gamma (\bar B^0 \to \pi^+ e^- \bar\nu) = (5.1\pm 1.1)\,|V_{ub}|^2\, 10^{12}\,{\rm s^{-1}}$, $\Gamma ( D^0 \to \pi^- e^+ \nu) = (8.0\pm 1.7)\,|V_{cd}|^2\, 10^{10}\,{\rm s^{-1}}$, $\Gamma (\bar B^0 \to \rho^+ e^- \bar\nu) = (1.2\pm 0.4\,)\,|V_{ub}|^2\, 10^{13}\,{\rm s^{-1}}$ and $\Gamma (D^0 \to \rho^- e^+\nu) = (2.4\pm 0.7)\,|V_{cd}|^2\, 10^{9}\,{\rm s^{-1}}$.Comment: 23 pages, 12 figures included as uu-encoded file, needs REVTEX, TUM--T31--39/9

Leptonic Decay Constants of DsD_{s} and BsB_{s} Mesons at Finite Temperature

In the present work, $D_{s}$ and $B_{s}$ meson parameters are investigated in the framework of thermal QCD sum rules. The temperature dependence of the mass and the leptonic decay constants are investigated by using Borel transform sum rules and Hilbert moment sum rules. To increase sensitivity, the vacuum contributions are subtracted from thermal expressions and the temperature dependences of the leptonic decay constants and meson masses are studied.Comment: 9 pages, 1 table, 4 figure

Higher Resonance Contamination of pi NN Couplings Obtained Via the Three-Point Function Method in QCD Sum Rules

We investigate the size of potential higher pseudoscalar resonance contaminations of the estimates of isospin-conserving and isospin-violating $\pi NN$ couplings obtained using the 3-point function method in QCD sum rules. For the isospin-conserving case it is shown that conventional models of the isovector pseudoscalar spectral function imply resonance decay constants large enough to create significant contaminations, and that assuming these models are incorrect, and that the decay constants are actually much smaller, implies physically implausible values for the flavor-breaking quark condensate ratios. For the isospin-violating case it is shown explicitly that such resonance contamination is unavoidably present and precludes using the 3-point function method as a means of estimating the at present unmeasured isospin-violating $\pi NN$ couplings.Comment: 8 page

Improved Determination of the Mass of the 1−+1^{-+} Light Hybrid Meson From QCD Sum Rules

We calculate the next-to-leading order (NLO) $\alpha_s$-corrections to the contributions of the condensates $$ and $^2$ in the current-current correlator of the hybrid current g\barq(x)\gamma_{\nu}iF_{\mu\nu}^aT^aq(x) using the external field method in Feynman gauge. After incorporating these NLO contributions into the Laplace sum-rules, the mass of the $J^{PC}$=$1^{-+}$ light hybrid meson is recalculated using the QCD sum rule approach. We find that the sum rules exhibit enhanced stability when the NLO $\alpha_s$-corrections are included in the sum rule analysis, resulting in a $1^{-+}$ light hybrid meson mass of approximately 1.6 GeV.Comment: revtex4, 10 pages, 7 eps figures embedded in manuscrip

Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice

Insulin resistance and impaired glucose homoeostasis are important indicators of Type 2 diabetes and are early risk factors of AD (Alzheimer's disease). An essential feature of AD pathology is the presence of BACE1 (β-site amyloid precursor protein-cleaving enzyme 1), which regulates production of toxic amyloid peptides. However, whether BACE1 also plays a role in glucose homoeostasis is presently unknown. We have used transgenic mice to analyse the effects of loss of BACE1 on body weight, and lipid and glucose homoeostasis. BACE1−/− mice are lean, with decreased adiposity, higher energy expenditure, and improved glucose disposal and peripheral insulin sensitivity than wild-type littermates. BACE1−/− mice are also protected from diet-induced obesity. BACE1-deficient skeletal muscle and liver exhibit improved insulin sensitivity. In a skeletal muscle cell line, BACE1 inhibition increased glucose uptake and enhanced insulin sensitivity. The loss of BACE1 is associated with increased levels of UCP1 (uncoupling protein 1) in BAT (brown adipose tissue) and UCP2 and UCP3 mRNA in skeletal muscle, indicative of increased uncoupled respiration and metabolic inefficiency. Thus BACE1 levels may play a critical role in glucose and lipid homoeostasis in conditions of chronic nutrient excess. Therefore strategies that ameliorate BACE1 activity may be important novel approaches for the treatment of diabetes

Flavour SU(3) Symmetry in Charmless B Decays

QCD sum rules are used to estimate the flavour SU(3)-symmetry violation in two-body B decays to pions and kaons. In the factorizable amplitudes the SU(3)-violation manifests itself in the ratio of the decay constants f_K/f_pi and in the differences between the B->K, B_s->K and B->pi form factors. These effects are calculated from the QCD two-point and light-cone sum rules, respectively, in terms of the strange quark mass and the ratio of the strange and nonstrange quark-condensate densities. Importantly, QCD sum rules predict that SU(3) breaking in the heavy-to-light form factors can be substantial and does not vanish in the heavy-quark mass limit. Furthermore, we investigate the strange-quark mass dependence of nonfactorizable effects in the B->K pi decay amplitudes. Taking into account these effects we estimate the accuracy of several SU(3)-symmetry relations between charmless B-decay amplitudes.Comment: Two references added, version to be published in Phys.Rev.D, 21 pages, 12 postscript figure

Fast food consumption and gestational diabetes incidence in the SUN project

Background: Gestational diabetes prevalence is increasing, mostly because obesity among women of reproductive age is continuously escalating. We aimed to investigate the incidence of gestational diabetes according to the consumption of fast food in a cohort of university graduates. Methods: The prospective dynamic ‘‘Seguimiento Universidad de Navarra’’ (SUN) cohort included data of 3,048 women initially free of diabetes or previous gestational diabetes who reported at least one pregnancy between December 1999 and March 2011. Fast food consumption was assessed through a validated 136-item semi-quantitative food frequency questionnaire. Fast food was defined as the consumption of hamburgers, sausages, and pizza. Three categories of fast food were established: low (0–3 servings/month), intermediate (.3 servings/month and #2 servings/week) and high (.2 servings/week). Non-conditional logistic regression models were used to adjust for potential confounders. Results: We identified 159 incident cases of gestational diabetes during follow-up. After adjusting for age, baseline body mass index, total energy intake, smoking, physical activity, family history of diabetes, cardiovascular disease/hypertension at baseline, parity, adherence to Mediterranean dietary pattern, alcohol intake, fiber intake, and sugar-sweetened soft drinks consumption, fast food consumption was significantly associated with a higher risk of incident gestational diabetes, with multivariate adjusted OR of 1.31 (95% conficence interval [CI]:0.81–2.13) and 1.86 (95% CI: 1.13–3.06) for the intermediate and high categories, respectively, versus the lowest category of baseline fast food consumption (p for linear trend: 0.007). Conclusion: Our results suggest that pre-pregnancy higher consumption of fast food is an independent risk factor for gestational diabetes