Nutritional supplements and infection in the elderly: why do the findings conflict?

BACKGROUND: Most of the randomized placebo-controlled trials that have examined the clinical effects of multivitamin-mineral supplements on infection in the elderly have shown no significant effect. The exceptions are three such trials, all using a supplement with the same composition, and all claiming dramatic benefits: a frequently cited study published in 1992, which reported a 50% reduction in the number of days of infection (NDI), and two 2002 replication studies. Questions have been raised about the 1992 report; a second report in 2001 based on the same trial, but describing effects of the supplement on cognitive functions, has been retracted by Nutrition. The primary purpose of the present paper is to evaluate the claims about the effects of supplements on NDI in the two replication reports. METHODS: Examination of internal consistency (outcomes of statistical tests versus reported data); comparison of variability of NDI across individuals in these two reports with variability in other trials; estimation of the probability of achieving the reported close agreement with the original finding. RESULTS: The standard deviations of NDI and levels of statistical significance reported are profoundly inconsistent. The reported standard deviations of NDI are consistently below what other studies have found. The reported percent reductions in NDI agree too closely with the original study. CONCLUSION: The claims of reduced NDI in the two replication reports should be questioned, which also adds to concerns about the 1992 study. It follows that there is currently no trustworthy evidence from randomized placebo-controlled clinical trials that favors the use of vitamin-mineral supplements to reduce infection in the elderly

HIV-1 Nef Protein Structures Associated with Brain Infection and Dementia Pathogenesis

The difference between regional rates of HIV-associated dementia (HAD) in patients infected with different subtypes of HIV suggests that genetic determinants exist within HIV that influence the ability of the virus to replicate in the central nervous system (in Uganda, Africa, subtype D HAD rate is 89%, while subtype A HAD rate is 24%). HIV-1 nef is a multifunctional protein with known toxic effects in the brain compartment. The goal of the current study was to identify if specific three-dimensional nef structures may be linked to patients who developed HAD. HIV-1 nef structures were computationally derived for consensus brain and non-brain sequences from a panel of patients infected with subtype B who died due to varied disease pathologies and consensus subtype A and subtype D sequences from Uganda. Site directed mutation analysis identified signatures in brain structures that appear to change binding potentials and could affect folding conformations of brain-associated structures. Despite the large sequence variation between HIV subtypes, structural alignments confirmed that viral structures derived from patients with HAD were more similar to subtype D structures than to structures derived from patient sequences without HAD. Furthermore, structures derived from brain sequences of patients with HAD were more similar to subtype D structures than they were to their own non-brain structures. The potential finding of a brain-specific nef structure indicates that HAD may result from genetic alterations that alter the folding or binding potential of the protein

Native T1 values identify myocardial changes and stratify disease severity in patients with Duchenne muscular dystrophy

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked, inherited disorder causing dilated cardiomyopathy with variable onset and progression. Currently we lack objective markers of the effect of therapies targeted towards preventing progression of subclinical cardiac disease. Thus, our aim was to compare the ability of native T1 and extracellular volume (ECV) measurements to differentiate risk of myocardial disease in DMD and controls. METHODS: Twenty boys with DMD and 16 age/gender-matched controls without history predisposing to cardiac fibrosis, but with a clinical indication for cardiovascular magnetic resonance (CMR) evaluation, underwent CMR with contrast. Data points collected include left ventricular ejection fraction (LVEF), left ventricular mass, and presence of late gadolinium enhancement (LGE). Native T1, and ECV regional mapping were obtained using both a modified Look-Locker (MOLLI) and saturation recovery single shot sequence (SASHA) on a 1.5T scanner. Using ordinal logistic regression models, controlling for age and LVEF, LGE-free septal we evaluated the ability native T1 and ECV assessments to differentiate levels of cardiomyopathy. RESULTS: Twenty DMD subjects aged 14.4 ± 4 years had an LVEF of 56.3 ± 7.4 %; 12/20 had LGE, all confined to the lateral wall. Sixteen controls aged 16.1 ± 2.2 years had an LVEF 60.4 ± 5.1 % and no LGE. Native T1 and ECV values were significantly higher in the DMD group (p < 0.05) with both MOLLI and SASHA imaging techniques. Native T1 demonstrated a 50 % increase in the ability to predict disease state (control, DMD without fibrosis, DMD with fibrosis). ECV demonstrated only the ability to predict presence of LGE, but could not distinguish between controls and DMD without fibrosis. CONCLUSIONS: LGE-spared regions of boys with DMD have significantly different native T1 and ECV values compared to controls. Native T1 measurements can identify early changes in DMD patients without the presence of LGE and help predict disease severity more effectively than ECV. Native T1 may be a novel outcome measure for early cardiac therapies in DMD and other cardiomyopathies

Bioreactor for microalgal cultivation systems: strategy and development

Microalgae are important natural resources that can provide food, medicine, energy and various bioproducts for nutraceutical, cosmeceutical and aquaculture industries. Their production rates are superior compared to those of terrestrial crops. However, microalgae biomass production on a large scale is still a challenging problem in terms of economic and ecological viability. Microalgal cultivation system should be designed to maximize production with the least cost. Energy efficient approaches of using light, dynamic mixing to maximize use of carbon dioxide (CO2) and nutrients and selection of highly productive species are the main considerations in designing an efficient photobioreactor. In general, optimized culture conditions and biological responses are the two overarching attributes to be considered for photobioreactor design strategies. Thus, fundamental aspects of microalgae growth, such as availability of suitable light, CO2 and nutrients to each growing cell, suitable environmental parameters (including temperature and pH) and efficient removal of oxygen which otherwise would negatively impact the algal growth, should be integrated into the photobioreactor design and function. Innovations should be strategized to fully exploit the wastewaters, flue-gas, waves or solar energy to drive large outdoor microalgae cultivation systems. Cultured species should be carefully selected to match the most suitable growth parameters in different reactor systems. Factors that would decrease production such as photoinhibition, self-shading and phosphate flocculation should be nullified using appropriate technical approaches such as flashing light innovation, selective light spectrum, light-CO2 synergy and mixing dynamics. Use of predictive mathematical modelling and adoption of new technologies in novel photobioreactor design will not only increase the photosynthetic and growth rates but will also enhance the quality of microalgae composition. Optimizing the use of natural resources and industrial wastes that would otherwise harm the environment should be given emphasis in strategizing the photobioreactor mass production. To date, more research and innovation are needed since scalability and economics of microalgae cultivation using photobioreactors remain the challenges to be overcome for large-scale microalgae production

Myocardial Strain Using Cardiac MR Feature Tracking and Speckle Tracking Echocardiography in Duchenne Muscular Dystrophy Patients

Duchenne muscular dystrophy (DMD) is an inherited X-linked disorder with an incidence of 1 in 3500 male births, and cardiomyopathy is becoming the leading cause of death. While Cardiac MRI (CMR) and late gadolinium enhancement (LGE) are important tools in recognizing myocardial involvement, myocardial strain imaging may demonstrate early changes and allow patients to avoid gadolinium contrast. We performed CMR feature tracking (FT) and echo-based speckle tracking (STE) strain measures on DMD patients and age/sex matched controls who had received a CMR with contrast and transthoracic echocardiogram. Data were collected for longitudinal strain in the apical four-chamber view and circumferential strain in the mid-papillary parasternal short axis. Segmental wall analysis was performed and compared with the presence of LGE. Data were analyzed using student’s t tests or one-way ANOVA adjusting for multiple comparisons. We measured 24 subjects with DMD and 8 controls. Thirteen of 24 DMD subjects were LGE positive only in the lateral segments in short-axis views. Average circumferential strain (CS) measured by FT was significantly decreased in DMD compared to controls (− 18.8 ± 6.1 vs. − 25.5 ± 3.2; p < 0.001) and showed significant differences in the anterolateral, inferolateral, and inferior segments. Average CS by STE trended towards significance (p = 0.06) but showed significance in only the inferior segment. FT showed significant differences in the inferolateral segment between LGE positive (− 15.5 ± 9.0) and LGE negative (− 18.2 ± 8.3) in DMD subjects compared to controls (− 28.6 ± 7.3; p ≤ 0.04). FT also showed significant differences between anteroseptal and inferolateral segments within LGE-positive (p < 0.003) and LGE-negative (p < 0.03) DMD subjects while STE did not. There were no significant differences in longitudinal strain measures. CMR-FT-derived myocardial strain was able to demonstrate differences between subjects with DMD and controls not detected by STE. FT was also able to demonstrate differences in LGE-positive and LGE-negative segments within patients with DMD. FT may be able to predict LGE-positive segments in DMD without the use of gadolinium contrast

Non-Hfe iron overload: Is Phlebotomy the answer?

Iron is an essential factor for life, however a physiologically optimal balance is critical. In this article we explore the role of iron as a co-factor in a range of chronic liver diseases and how it may contribute to the development of liver injury, fibrosis, cirrhosis and ultimately hepatocellular carcinoma. Whilst iron depletion therapy through phlebotomy is the most effective method of reducing iron stores, it is unclear whether this offers utility in the therapy of liver diseases in which iron is not the primary insult resulting in tissue injury. Here we examine the emerging evidence in the field of non-HFE hereditary haemochromatosis conditions associated with iron overload – is phlebotomy the answer