Deletion of the ghrelin receptor GHSR corrects the trabecular, but not the cortical bone changes in the femoral head of ob/ob mice

Background: There exists an intriguing and complex relationship between fat and bone cells with respect to aging and osteoporosis, which is mediated in part by leptin. Genetically obese mice (ob/ob), that lack leptin, have aheterogeneous bone phenotype, with differential effects on cortical and trabecular compartments. Besides its role in bone metabolism, leptin is most well known for its anorexigenic properties. Opposed in action to leptin is ghrelin, a potent orexigenic peptide hormone derived from the stomach. Ghrelin and leptin also act as each other’s antagonists in gonadal and immune system function.Objective: To determine if ghrelin opposes leptin action on bone metabolism.Methods: Characterization of femoral micro-architecture in 6 months old male wild type, ob/ob, ghrelin receptor knockout (Ghsr -/-), and ob/ob.Ghsr-/- mice using micro-computed tomography.Results: Deletion of Ghsr alone did not significantly alter bone micro-architecture in wild type mice. Deletion of leptin reduced cortical volume and thickness in the femoral head of wild type mice, while it increased endocortical volume. Tissue volume remained unaffected. Conversely, deletion of leptin increased trabecular bone volume, trabecular number and connectivity in wild type mice. Additional deletion of Ghsr in ob/ob mice restored the changes to wild type levels in trabecular bone, but not in cortical bone (all not significant).Conclusion: We found that leptin deficiency has a negative effect on cortical and a positive effect on trabecular bone micro-architecture, confirming the heterogeneous skeletal effects observed by others in ob/ob mice. Knocking out ghrelin signaling compensates for the effect of leptin deficiency on trabecular bone. These observations demonstrate the positive activity of ghrelin signaling in bone, and suggest that ghrelin and leptin have opposing actions on bone metabolism

Alignment Timescale of the Microquasar GRO J1655-40

The microquasar GRO J1655-40 has a black hole with spin angular momentum apparently misaligned to the orbital plane of its companion star. We analytically model the system with a steady state disc warped by Lense-Thirring precession and find the timescale for the alignment of the black hole with the binary orbit. We make detailed stellar evolution models so as to estimate the accretion rate and the lifetime of the system in this state. The secondary can be evolving at the end of the main sequence or across the Hertzsprung gap. The mass-transfer rate is typically fifty times higher in the latter case but we find that, in both cases, the lifetime of the mass transfer state is at most a few times the alignment timescale. The fact that the black hole has not yet aligned with the orbital plane is therefore consistent with either model. We conclude that the system may or may not have been counter-aligned after its supernova kick but that it is most likely to be close to alignment rather than counteralignment now.Comment: Accepted for publication in MNRA

Protein quality as a complementary functional unit in life cycle assessment (LCA)

Goal and theoretical commentary A number of recent life cycle assessment (LCA) studies have concluded that animal-sourced foods should be restricted—or even avoided—within the human diet due to their relatively high environmental impacts (particularly those from ruminants) compared with other protein-rich foods (mainly protein-rich plant foods). From a nutritional point of view, however, issues such as broad nutrient bioavailability, amino acid balances, digestibility and even non-protein nutrient density (e.g., micronutrients) need to be accounted for before making such recommendations to the global population. This is especially important given the contribution of animal sourced foods to nutrient adequacy in the global South and vulnerable populations of high-income countries (e.g., children, women of reproductive age and elderly). Often, however, LCAs simplify this reality by using ‘protein’ as a functional unit in their models and basing their analyses on generic nutritional requirements. Even if a ‘nutritional functional unit’ (nFU) is utilised, it is unlikely to consider the complexities of amino acid composition and subsequent protein accretion. The discussion herein focuses on nutritional LCA (nLCA), particularly on the usefulness of nFUs such as ‘protein,’ and whether protein quality should be considered when adopting the nutrient as an (n)FU. Further, a novel and informative case study is provided to demonstrate the strengths and weaknesses of protein-quality adjustment. Case study methods To complement current discussions, we present an exploratory virtual experiment to determine how Digestible Indispensable Amino Acid Scores (DIAAS) might play a role in nLCA development by correcting for amino acid quality and digestibility. DIAAS is a scoring mechanism which considers the limiting indispensable amino acids (IAAs) within an IAA balance of a given food (or meal) and provides a percentage contribution relative to recommended daily intakes for IAA and subsequent protein anabolism; for clarity, we focus only on single food items (4 × animal-based products and 4 × plant-based products) in the current case exemplar. Further, we take beef as a sensitivity analysis example (which we particularly recommend when considering IAA complementarity at the meal-level) to elucidate how various cuts of the same intermediary product could affect the interpretation of nLCA results of the end-product(s). Recommendations First, we provide a list of suggestions which are intended to (a) assist with deciding whether protein-quality correction is necessary for a specific research question and (b) acknowledge additional uncertainties by providing mitigating opportunities to avoid misinterpretation (or worse, dis-interpretation) of protein-focused nLCA studies. We conclude that as relevant (primary) data availability from supply chain ‘gatekeepers’ (e.g., international agri-food distributors and processors) becomes more prevalent, detailed consideration of IAA provision of contrasting protein sources needs to be acknowledged—ideally quantitatively with DIAAS being one example—in nLCA studies utilising protein as a nFU. We also contend that future nLCA studies should discuss the complementarity of amino acid balances at the meal-level, as a minimum, rather than the product level when assessing protein metabolic responses of consumers. Additionally, a broader set of nutrients should ideally be included when evaluating “protein-rich foods” which provide nutrients that extend beyond amino acids, which is of particular importance when exploring dietary-level nLCA

Diagnostic accuracy of the Patient Health Questionnaire-9 for assessment of depression in type II diabetes mellitus and/or coronary heart disease in primary care

Background Depression is common among type 2 diabetes mellitus (DM2)/coronary heart disease (CHD) patients and is associated with adverse health effects. A promising strategy to reduce burden of disease is to identify patients at risk for depression in order to offer indicated prevention. This study aims to assess the diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9) to be used as a tool to identify high risk patients. Methods In this cross-sectional study, 586 consecutive DM2/CHD patients aged >18 were recruited through 23 general practices. PHQ-9 outcomes were compared to the Mini International Neuropsychiatric Interview (MINI), which was considered the reference standard. Diagnostic accuracy was evaluated for minor and major depression, comparing both sum- and algorithm based PHQ-9 scores. Results For minor depression, the optimal cut-off score was 8 (sensitivity 71%, specificity 71% and an AUC of 0.74). For major depression, the optimal cut-off score was 10 resulting in a sensitivity of 84%, a specificity of 82%, and an AUC of 0.88. The positive predictive value of the PHQ-9 algorithm for diagnosing minor and major depression was 25% and 33%, respectively. Limitations Two main limitations apply. MINI Interviewers were not blinded for PHQ-9 scores and less than 10% of all invited patients could be included in the analyses. This could have resulted in biased outcomes. Conclusions The PHQ-9 sum score performs well in identifying patients at high risk of minor and major depression. However, the PHQ-9 showed suboptimal results for diagnostic purposes. Therefore, it is recommended to combine the use of the PHQ-9 with further diagnostics to identify depression

Homocysteine levels and the risk of osteoporotic fracture

BACKGROUND: Very high plasma homocysteine levels are characteristic of homocystinuria, a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis. We therefore hypothesized that mildly elevated homocysteine levels might be related to age-related osteoporotic fractures. METHODS: We studied the association between circulating homocysteine levels and the risk of incident osteoporotic fracture in 2406 subjects, 55 years of age or older, who participated in two separate prospective, population-based studies. In the Rotterdam Study, there were two independent cohorts: 562 subjects in cohort 1, with a mean follow-up period of 8.1 years; and 553 subjects in cohort 2, with a mean follow-up period of 5.7 years. In the Longitudinal Aging Study Amsterdam, there was a single cohort of 1291 subjects, with a mean follow-up period of 2.7 years. Multivariate Cox proportional-hazards regression mode

Protein quality as a complementary functional unit in life cycle assessment (LCA)

Goal and theoretical commentary. A number of recent life cycle assessment (LCA) studies have concluded that animal-sourced foods should be restricted—or even avoided—within the human diet due to their relatively high environmental impacts (particularly those from ruminants) compared with other protein-rich foods (mainly protein-rich plant foods). From a nutritional point of view, however, issues such as broad nutrient bioavailability, amino acid balances, digestibility and even non-protein nutrient density (e.g., micronutrients) need to be accounted for before making such recommendations to the global population. This is especially important given the contribution of animal sourced foods to nutrient adequacy in the global South and vulnerable populations of high-income countries (e.g., children, women of reproductive age and elderly). Often, however, LCAs simplify this reality by using ‘protein’ as a functional unit in their models and basing their analyses on generic nutritional requirements. Even if a ‘nutritional functional unit’ (nFU) is utilised, it is unlikely to consider the complexities of amino acid composition and subsequent protein accretion. The discussion herein focuses on nutritional LCA (nLCA), particularly on the usefulness of nFUs such as ‘protein,’ and whether protein quality should be considered when adopting the nutrient as an (n)FU. Further, a novel and informative case study is provided to demonstrate the strengths and weaknesses of protein-quality adjustment. Case study methods. To complement current discussions, we present an exploratory virtual experiment to determine how Digestible Indispensable Amino Acid Scores (DIAAS) might play a role in nLCA development by correcting for amino acid quality and digestibility. DIAAS is a scoring mechanism which considers the limiting indispensable amino acids (IAAs) within an IAA balance of a given food (or meal) and provides a percentage contribution relative to recommended daily intakes for IAA and subsequent protein anabolism; for clarity, we focus only on single food items (4 × animal-based products and 4 × plant-based products) in the current case exemplar. Further, we take beef as a sensitivity analysis example (which we particularly recommend when considering IAA complementarity at the meal-level) to elucidate how various cuts of the same intermediary product could affect the interpretation of nLCA results of the end-product(s). Recommendations. First, we provide a list of suggestions which are intended to (a) assist with deciding whether protein-quality correction is necessary for a specific research question and (b) acknowledge additional uncertainties by providing mitigating opportunities to avoid misinterpretation (or worse, dis-interpretation) of protein-focused nLCA studies. We conclude that as relevant (primary) data availability from supply chain ‘gatekeepers’ (e.g., international agri-food distributors and processors) becomes more prevalent, detailed consideration of IAA provision of contrasting protein sources needs to be acknowledged—ideally quantitatively with DIAAS being one example—in nLCA studies utilising protein as a nFU. We also contend that future nLCA studies should discuss the complementarity of amino acid balances at the meal-level, as a minimum, rather than the product level when assessing protein metabolic responses of consumers. Additionally, a broader set of nutrients should ideally be included when evaluating “protein-rich foods” which provide nutrients that extend beyond amino acids, which is of particular importance when exploring dietary-level nLCA