ABSTRACT
Annual costs are enormous for musculoskeletal diseases such as osteoporosis and sarcopenia and for bone and muscle injuries, costing billions annually in health care. Although it is clear ...that muscle and bone development, growth, and function are connected, and that muscle loads bone, little is known regarding cellular and molecular interactions between these two tissues. A conference supported by the National Institutes of Health (NIH) and the American Society for Bone and Mineral Research (ASBMR) was held in July 2012 to address the enormous burden of musculoskeletal disease. National and international experts in either bone or muscle presented their findings and their novel hypotheses regarding muscle‐bone interactions to stimulate the exchange of ideas between these two fields. The immediate goal of the conference was to identify critical research themes that would lead to collaborative research interactions and grant applications focusing on interactions between muscle and bone. The ultimate goal of the meeting was to generate a better understanding of how these two tissues integrate and crosstalk in both health and disease to stimulate new therapeutic strategies to enhance and maintain musculoskeletal health.
Functionality of Sugars in Foods and Health Clemens, Roger A.; Jones, Julie M.; Kern, Mark ...
Comprehensive reviews in food science and food safety,
20/May , Letnik:
15, Številka:
3
Journal Article
Recenzirano
Overweight and obesity are global health problems that affect more than 1.9 billion adults who are overweight, and of these 600 million are obese. In the United States, these problems affect 60% of ...the population. Critical to these statistics is the association with increased risk of cardiovascular disease, type 2 diabetes, and metabolic syndrome among other noncommunicable diseases. Many factors, including sugars, have been charged as potential causes. However, obesity and overweight and their attendant health problems continue to increase despite the fact that there is a decline in the consumption of sugars. Sugars vary in their types and structure. From a food science perspective, sugars present an array of attributes that extend beyond taste, flavor, color, and texture to aspects such as structure and shelf‐life of foods. From a public health perspective, there is considerable controversy about the effect of sugar relative to satiety, digestion, and noncommunicable diseases. This comprehensive overview from experts in food science, nutrition and health, sensory science, and biochemistry describes the technical and functional roles of sugar in food production, provides a balanced evidence‐based assessment of the literature and addresses many prevalent health issues commonly ascribed to sugar by the media, consumer groups, international scientific organizations, and policy makers. The preponderance of the evidence indicates that sugar as such does not contribute to adverse health outcomes when consumed under isocaloric conditions. The evidence generally indicates, as noted by the 2010 Dietary Guidelines Advisory Committee, that sugar, like any other caloric macronutrient, such as protein and fat, when consumed in excess leads to conditions such as obesity and related comorbidities. More recently, the 2015‐2020 Dietary Guidelines for Americans recommended limiting dietary sugar to 10% of total energy in an effort to reduced the risk of these noncommunicable diseases.
Objective
We hypothesized that specific mutations in the β‐glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous ...Parkinson's disease (PD) patients, whereas non‐neuropathic GD mutations confer intermediate progression rates.
Methods
A total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of genetic variation in GBA on longitudinal cognitive decline were evaluated using mixed random and fixed effects and Cox proportional hazards models.
Results
Overall, 10.3% of patients with PD and GBA sequencing carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence interval CI, 1.60–6.25) and a hastened decline in Mini–Mental State Exam scores compared to noncarriers (p = 0.0009). Carriers of complex GBA alleles (0.7%) had an HR of 3.22 (95% CI, 1.18–8.73; p = 0.022). By contrast, the common, non‐neuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92–4.18) or nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89–2.05) did not reach significance.
Interpretation
Mutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into “high gear.” These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674–685
Variants in the
gene have been identified as a common risk factor for Parkinson's disease (PD). In addition to pathogenic mutations (those associated with Gaucher disease), a number of ...'non-pathogenic' variants also occur at increased frequency in PD. Previous studies have reported that pathogenic variants adversely affect the clinical course of PD. The role of 'non-pathogenic'
variants on PD course is less clear. In this study, we report the effect of
variants in incident PD patients with long-term follow-up.
The study population consisted of patients in the Cambridgeshire Incidence of Parkinson's disease from General Practice to Neurologist and Parkinsonism: Incidence, Cognition and Non-motor heterogeneity in Cambridgeshire cohorts. Patients were grouped into non-carriers, carriers of 'non-pathogenic'
variants and carriers of pathogenic
mutations. Survival analyses for time to development of dementia, postural instability and death were carried out. Cox regression analysis controlling for potential confounders were used to determine the impact of
variants on these outcome measures.
variants were identified in 14.4% of patients. Pathogenic and 'non-pathogenic'
variants were associated with the accelerated development of dementia and a more aggressive motor course. Pathogenic
variants were associated with earlier mortality in comparison with non-carriers, independent of the development of dementia.
variants, including those not associated with Gaucher disease, are common in PD and result in a more aggressive disease course.
Myostatin inhibits skeletal muscle growth. The humanised monoclonal antibody LY2495655 (LY) binds and neutralises myostatin. We aimed to test whether LY increases appendicular lean body mass (aLBM) ...and improves physical performance in older individuals who have had recent falls and low muscle strength and power.
In this proof-of-concept, randomised, placebo-controlled, double-blind, parallel, multicentre, phase 2 study, we recruited patients aged 75 years or older who had fallen in the past year from 21 investigator sites across Argentina, Australia, France, Germany, Sweden, and the USA. Eligible patients had low performance on hand grip strength and chair rise tests, tested with the procedure described by Guralnik and colleagues. Participants were stratified by country, age, hand grip strength, and performance on the chair rise test, and were randomly assigned (1:1) by a computer-generated random sequence to receive subcutaneous injections of placebo or 315 mg LY at weeks 0 (randomisation visit), 4, 8, 12, 16, and 20, followed by 16 weeks observation. The primary outcome was change in aLBM from baseline to 24 weeks. We measured physical performance as secondary outcomes (four-step stair climbing time, usual gait speed, and time to rise five times from a chair without arms, or with arms for participants unable to do it without arms) and exploratory outcomes (12-step stair climbing test, 6-min walking distance, fast gait speed, hand grip strength, and isometric leg extension strength). Efficacy analyses included all randomly assigned patients who received at least one dose and had a baseline and at least one subsequent measure. The primary analysis and all other tests of treatment effect (except physical performance tests) were done at a two-sided alpha level of 0·05. Tests of treatment effect on physical performance tests were done at a pre-specified two-sided alpha level of 0·1. This trial is registered with ClinicalTrials.gov, number NCT01604408.
Between June 19, 2012, and Dec 12, 2013, we screened 365 patients. 99 were randomly assigned to receive placebo and 102 to receive LY. Treatment was completed in 85 (86%) of patients given placebo and in 82 (80%) given LY. At 24 weeks, the least-squares mean change in aLBM was -0·123 kg (95% CI -0·287 to 0·040) in the placebo group and 0·303 kg (0·135 to 0·470) in the LY group, a difference of 0·43 kg (95% CI 0·192 to 0·660; p<0·0001). Stair climbing time (four-step and 12-step tests), chair rise with arms, and fast gait speed improved significantly from baseline to week 24 with differences between LY and placebo of respectively -0·46 s (p=0·093), -1·28 s (p=0·011), -4·15 s (p=0·054), and 0·05 m/s (p=0·088). No effect was detected for other performance-based measures. Injection site reactions were recorded in nine (9%) patients given placebo and in 31 (30%) patients given LY (p<0·0001), and were generally mild, and led to treatment discontinuation in two patients given LY.
Our findings show LY treatment increases lean mass and might improve functional measures of muscle power. Although additional studies are needed to confirm these results, our data suggest LY should be tested for its potential ability to reduce the risk of falls or physical dependency in older weak fallers.
Eli Lilly and Company.
Aloe products are increasingly valued as ingredients in food supplements and as flavoring agents. The global Aloe vera market is varied, large, growing, and increasingly important in food, cosmetics, ...and medicines. Aloin, an anthraquinone glycoside, is one of the major components by weight of the anthraquinone derivatives of Aloe vera gel. Principal metabolites, aloe emodin and emodin, are a source of debate concerning toxic vs salutary effects, hence the accurate toxicological characterization of these compounds has become increasingly important. The purpose of this study was to determine the genotoxic profile of a stabilized Aloe vera juice product derived from the inner filet and marketed as a beverage currently sold in the European Union containing 8 to 10 ppm aloin and a mixture of purified aloin A and B. The present data confirm that a commercial stabilized Aloe vera gel intended for consumption as a juice beverage is not genotoxic. Furthermore, both aloin A and B were negative in the same assays and therefore are also not genotoxic. These results are consistent with the work of other groups and contrast with data obtained using products containing the Aloe vera latex hydroxyanthracene derivatives (HADs).
We conducted this cross-sectional population study with a healthy multi-ethnic urban population (n = 577) in Malaysia, combining nutritional assessments with cardiometabolic biomarkers defined by ...lipid, atherogenic lipoproteins, inflammation and insulin resistance. We found diametrically opposing associations of carbohydrate (246·6 ± 57·7 g, 54·3 ± 6·5%-TEI) and fat (total = 64·5 ± 19·8 g, 31·6 ± 5·5%-TEI; saturated fat = 14·1 ± 2·7%-TEI) intakes as regards waist circumference, HDL-C, blood pressure, glucose, insulin and HOMA2-IR as well as the large-LDL and large-HDL lipoprotein particles. Diets were then differentiated into either low fat (LF, <30% TEI or <50 g) or high fat (HF, >35% TEI or >70 g) and low carbohydrate (LC, <210 g) or high carbohydrate (HC, >285 g) which yielded LFLC, LFHC, HFLC and HFHC groupings. Cardiometabolic biomarkers were not significantly different (P > 0.05) between LFLC and HFLC groups. LFLC had significantly higher large-LDL particle concentrations compared to HFHC. HOMA-IR2 was significantly higher with HFHC (1·91 ± 1·85, P < 0·001) versus other fat-carbohydrate combinations (LFLC = 1·34 ± 1·07, HFLC = 1·41 ± 1·07; LFHC = 1·31 ± 0·93). After co-variate adjustment, odds of having HOMA2-IR >1.7 in the HFHC group was 2.43 (95% CI: 1·03, 5·72) times more compared to LFLC while odds of having large-LDL <450 nmol/L in the HFHC group was 1.91 (95% CI: 1·06, 3·44) more compared to latter group. Our data suggests that a HFHC dietary combination in Malaysian adults is associated with significant impact on lipoprotein particles and insulin resistance.
Severe imbalance in iron metabolism among SARS-CoV-2 infected patients is prominent in every symptomatic (mild, moderate to severe) clinical phase of COVID-19. Phase-I - Hypoxia correlates with ...reduced O
2
transport by erythrocytes, overexpression of HIF-1α, altered mitochondrial bioenergetics with host metabolic reprogramming (HMR). Phase-II - Hyperferritinemia results from an increased iron overload, which triggers a fulminant proinflammatory response - the acute cytokine release syndrome (CRS). Elevated cytokine levels (i.e. IL6, TNFα and CRP) strongly correlates with altered ferritin/TF ratios in COVID-19 patients. Phase-III - Thromboembolism is consequential to erythrocyte dysfunction with heme release, increased prothrombin time and elevated D-dimers, cumulatively linked to severe coagulopathies with life-threatening outcomes such as ARDS, and multi-organ failure. Taken together, Fe-R-H dysregulation is implicated in every symptomatic phase of COVID-19. Fe-R-H regulators such as lactoferrin (LF), hemoxygenase-1 (HO-1), erythropoietin (EPO) and hepcidin modulators are innate bio-replenishments that sequester iron, neutralize iron-mediated free radicals, reduce oxidative stress, and improve host defense by optimizing iron metabolism. Due to its pivotal role in 'cytokine storm', ferroptosis is a potential intervention target. Ferroptosis inhibitors such as ferrostatin-1, liproxstatin-1, quercetin, and melatonin could prevent mitochondrial lipid peroxidation, up-regulate antioxidant/GSH levels and abrogate iron overload-induced apoptosis through activation of Nrf2 and HO-1 signaling pathways. Iron chelators such as heparin, deferoxamine, caffeic acid, curcumin, α-lipoic acid, and phytic acid could protect against ferroptosis and restore mitochondrial function, iron-redox potential, and rebalance Fe-R-H status. Therefore, Fe-R-H restoration is a host biomarker-driven potential combat strategy for an effective clinical and post-recovery management of COVID-19.
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