Acute caffeine intake in humans reduces post exercise performance in learning and memory.

OBJECTIVE: To clarify the acute effect of caffeine on postexercise memory and learning performance. METHODS: Eight male slow-to-normal caffeine metabolizers, unhabituated to caffeine, were recruited into this randomized, double blind, placebo controlled, cross over study. Caffeine (150 mg) or the placebo was consumed one hour prior to two 30 min submaximal cycling sessions. Blood was collected at the beginning, after 20 and 35 min of exercise and 30 min postexercise. Mature brain-derived neurotrophic factor (BDNF) and proBDNF concentrations were determined. Auditory memory was assessed immediately, 30 min and 24 h postexercise. RESULTS: Participants averaged lower scores in every measure of learning and memory after ingesting caffeine compared to the placebo. Although the mean did not differ significantly for all measures, significant differences were found between the caffeine and placebo groups for the three indices; learning over time, short-term index and retroactive interference. The ratio of serum mBDNF:proBDNF increased with exercise across all time points. No significant difference in the mBDNF:proBDNF ratio was observed between treatment groups. CONCLUSION: The consumption of caffeine prior to exercise may impair an unhabituated individual's capacity to learn and recall auditory information postexercise. However it is yet to be elucidated whether this is through caffeine's modulating effects on brain BDNF.

The effect of Trigonella foenum-graecum extract on prostate-specific antigen, and prostate function in otherwise healthy men with benign prostate hyperplasia.

The aim of this trial was to evaluate the effect of a standardised Trigonella foenum-graecum (Fenugreek) extract on the symptoms of benign prostate hyperplasia (BPH) using a double-blind randomised placebo controlled design. The study recruited 100 healthy males aged between 45 and 80 years with symptoms of BPH who recorded a minimum score of eight on the International Prostate Symptom Score. Participants were randomised to an oral dose of either 600mg Trigonella foenum-graceum per day or placebo for 12 weeks. The primary outcome measure was the International Prostate Symptom Score total and subdomain scores. The secondary outcomes were serum levels of the hormones (testosterone, free testosterone, and sex hormone binding globulin) prostate-specific antigen, and safety markers. The results indicated that Trigonella foenum-graceum did not have an effect on improving the symptoms of BPH. Hormone levels, safety markers, and prostate-specific antigen remained unchanged and within normal limits after 12 weeks, which adds to the safety profile of this specialised extract.

Oxidation of fish oil supplements in Australia.

Fish oils oxidise readily, forming primary and secondary oxidation products, which may be harmful for humans. Some recent studies reported that fish oil supplements in Australasia are oxidised above acceptable international limits, however other studies reported low levels of oxidation. This study employed peroxide and p-anisidine values determination to measure primary and secondary oxidation of fish oils in the Australian market. Of 26 supplements tested, 38% exceeded the limit for primary oxidation, 25% exceeded the limit for secondary oxidation and 33% exceeded the limit for total oxidation, according to international recommendations. Four specially marketed supplements were found to deliver significantly lower amounts of fish oil per capsule (165 vs. 577 mg, p = .007), yet cost significantly more on a per gram basis ($2.97 vs $0.39, p < .001). However, there were no differences in any oxidative markers between regular supplements and the specially marketed products.

A Diet Enriched with Red Sorghum Flaked Biscuits, Compared to a Diet Containing White Wheat Flaked Biscuits, Does Not Enhance the Effectiveness of an Energy-Restricted Meal Plan in Overweight and Mildly Obese Adults.

OBJECTIVES: Whole grain sorghum is a promising ingredient in foods, especially those targeting satiety and weight control. This study aimed to test weight loss effects of a whole grain red sorghum product incorporated into an energy-restricted diet. METHODS: Sixty subjects (46 females) were randomized to either a sorghum (intervention) or white wheat (control) group, receiving 45 g of flaked cereal biscuits to include daily in their prescribed diets for 12 weeks. Primary outcome was weight loss. Secondary outcomes included plasma glucose, glycosylated hemoglobin (HbA1c), insulin, total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triacylglycerides (TAG), interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), and total antioxidant capacity (TAC; measured at 0 and 12 weeks). RESULTS: After 12 weeks, there were no significant differences in weight loss or any clinical variables between a wheat control and sorghum cereal group in an energy-restricted diet. Equivalent amounts of weight were lost (p = 0.369) in both groups, and the majority of clinical indices such as fasting glucose, insulin, cholesterol, and key inflammatory biomarkers showed significant beneficial changes over time (p < 0.05). CONCLUSIONS: Although both groups experienced significant weight loss and general improvement in a number of clinical measures, no effects appeared specifically related to sorghum consumption. Further clinical trials are necessary to establish an evidence base for weight loss effects from chronic sorghum intake. Sorghum represents a viable, gluten-free grain alternative in the formulation of novel food products.

Visceral fat mass: is it the link between uric acid and diabetes risk?

BACKGROUND: Uric acid (UA) has been suggested as a novel risk factor for diabetes. However, its definite role in this prevalent disease is still the subject of much discussion because it is always accompanied with other major risk factors such as obesity and high visceral adiposity. In order to clarify the role of UA in diabetes, this study aimed to investigate the associations between plasma UA and fasting plasma glucose, HbA1c, lipid profile and inflammatory markers after accounting for the contribution of other diabetes risk factors such as BMI and VAT fat mass. METHODS: In the present cross-sectional study, 100 non-diabetic middle-aged males (n = 48) and females (n = 52) were recruited. Central fat distribution measures including android to gynoid fat ratio, VAT and subcutaneous adipose tissue (SAT) fat mass were determined using dual-energy X-ray absorptiometry (DXA). Biochemical analysis was done using methods well established for clinical and research laboratories. Multiple linear regression analysis was performed to analyse the association between plasma UA and the biochemical and central fat distribution measures. RESULTS: UA was positivly associated with body mass index (BMI) (r (98) = 0.42, P ≤ 0.001), android to gynoid fat ratio (r (98) = 0.62, P ≤ 0.001) and VAT fat mass (r (96) = 0.55, P ≤ 0.001). UA was also positively associated with plasma glucose (r (98) = 0.33, P ≤ 0.001), hemoglobin A1c (r (93) = 0.25, P = 0.014), plasma triglyceride (r s (95) = 0.40, P ≤ 0.001), HDL cholesterol (r (98) = - 0.61, P ≤ 0.001) and CRP (r s (98) = 0.23, P = 0.026). However, these associations were no longer significant after accounting for BMI or/and VAT fat mass. No significant association was observed between UA and SAT fat mass (r (97) = 0.02, P ≥ 0.05), Total cholesterol (r (98) = 0.03, P ≥ 0.05), LDL cholesterol (r (98) = 0.13, P ≥ 0.05), TNF-α (r (97) = 0.12, P ≥ 0.05) and IL-6 (r (96) = -0.02, P ≥ 0.05). CONCLUSION: Results from this study suggest, for the first time, that the association between plasma UA and glucose in a non-diabetic population is not direct but rather dependent on VAT fat mass.

Central kynurenine pathway shift with age in women.

Age is considered a dominant risk factor in the development of most neurodegenerative disorders. The kynurenine pathway, a major metabolic pathway of tryptophan is altered in the majority of neurodegenerative disorders. In this study, we have analysed CSF samples from 49 healthy women across a wide age range (0-90) for kynurenine pathway metabolites and the inflammatory marker neopterin. Our results show central tryptophan metabolism is increased with age in women, with an apparent shift towards the neurotoxin quinolinic acid. We also observed an increase in central levels of the inflammatory marker neopterin with age and a positive correlation between neopterin and kynurenine pathway activation. We conclude that, the changes that occur in the kynurenine pathway as a result of normal ageing are mechanistically linked to increased inflammatory signalling and have some explanatory potential with regard to age-associated degenerative diseases in the CNS. Management of health in ageing and (preventative) treatment would do well to look to the kynurenine pathway for potentially novel solutions. Both the inflammation marker neopterin and kynurenine pathway activity were increased with age in the CSF of female subjects. While levels of quinolinic acid (QUIN), picolinic acid (PIC), kynurenine and quinaldic acid (QA) were increased, 3-hydroxykynurenine (3HK) was decreased and 3-hydroxyanthranilic acid (3HAA) and kynurenic acid (KYNA) remained unchanged. Of particular interest is the increase in QUIN, a neuroexcitotoxin associated with neurodegeneration.

Does Research Training During Residency Promote Scholarship and Influence Career Choice? A Cross-Sectional Analysis of a 10-Year Cohort of the UCSF-PRIME Internal Medicine Residency Program.

PROBLEM: The Association of Program Directors in Internal Medicine, the Accreditation Council for Graduate Medical Education, the Alliance for Academic Internal Medicine, and the Carnegie Foundation report on medical education recommend creating individualized learning pathways during medical training so that learners can experience broader professional roles beyond patient care. Little data exist to support the success of these specialized pathways in graduate medical education. INTERVENTION: We present the 10-year experience of the Primary Care Medicine Education (PRIME) track, a clinical-outcomes research pathway for internal medicine residents at the University of California San Francisco (UCSF). We hypothesized that participation in an individualized learning track, PRIME, would lead to a greater likelihood of publishing research from residency and accessing adequate career mentorship and would be influential on subsequent alumni careers. CONTEXT: We performed a cross-sectional survey of internal medicine residency alumni from UCSF who graduated in 2001 through 2010. We compared responses of PRIME and non-PRIME categorical alumni. We used Pearson's chi-square and Student's t test to compare PRIME and non-PRIME alumni on categorical and continuous variables. OUTCOME: Sixty-six percent (211/319) of alumni responded to the survey. A higher percentage of PRIME alumni published residency research projects compared to non-PRIME alumni (64% vs. 40%; p = .002). The number of PRIME alumni identifying research as their primary career role was not significantly different from non-PRIME internal medicine residency graduates (35% of PRIME vs. 29% non-PRIME). Process measures that could explain these findings include adequate access to mentors (M 4.4 for PRIME vs. 3.6 for non-PRIME alumni, p < .001, on a 5-point Likert scale) and agreeing that mentoring relationships affected career choice (M 4.2 for PRIME vs. 3.7 for categorical alumni, p = .001). Finally, 63% of PRIME alumni agreed that their research experience during residency influenced their subsequent career choice versus 46% of non-PRIME alumni (p = .023). LESSONS LEARNED: Our results support the concept that providing residents with an individualized learning pathway focusing on clinical outcomes research during residency enables them to successfully publish manuscripts and access mentorship, and may influence subsequent career choice. Implementation of individualized residency program tracks that nurture academic interests along with clinical skills can support career development within medicine residency programs.

Characterisation of the kynurenine pathway in skin-derived fibroblasts and keratinocytes.

Acute UVB exposure triggers inflammation leading to the induction of indoleamine 2,3 dioxygenase (IDO1), one of the first enzymes in the kynurenine pathway (KP) for tryptophan degradation. However, limited studies have been undertaken to determine the catabolism of tryptophan within the skin. The aim of this study was two fold: (1) to establish if the administration of the proinflammatory cytokine interferon-gamma (IFN-γ) and/or UVB radiation elicits differential KP expression patterns in human fibroblast and keratinocytes; and (2) to evaluate the effect of KP metabolites on intracellular nicotinamide adenine dinucleotide (NAD(+) ) levels, and cell viability. Primary cultures of human fibroblasts and keratinocytes were used to examine expression of the KP at the mRNA level using qPCR, and at the protein level using immunocytochemistry. Cellular responses to KP metabolites were assessed by examining extracellular lactate dehydrogenase (LDH) activity and intracellular NAD(+) levels. Major downstream KP metabolites were analyzed using GC/MS and HPLC. Our data shows that the KP is fully expressed both in human fibroblasts and keratinocytes. Exposure to UVB radiation and/or IFN-γ causes significant changes in the expression pattern of downstream KP metabolites and enzymes. Exposure to various concentrations of KP metabolites showed marked differences in cell viability and intracellular NAD(+) production, providing support for involvement of the KP in the de novo synthesis of NAD(+) in the skin. This new information will have a significant impact on our understanding of the pathogenesis of UV related skin damage and the diagnosis of KP related disease states.

Effect of umbilical cord blood prefreeze variables on postthaw viability.

BACKGROUND: Assessment of the overall postthaw (PT) viability of an umbilical cord blood (UCB) unit is an important criterion for determining the quality of the unit for transplantation. Overall PT viability is a measure of cellular damage that can occur to the UCB during collection, storage, processing, freezing, and thawing. STUDY DESIGN AND METHODS: This study investigated factors measured before freezing of the UCB that could affect overall PT viability of the stem cell unit from 257 collected cord blood samples. The analysis included hematologic variables, cord blood collection characteristics, and stem cell separation and preservation factors. RESULTS: Each of the variables, postprocess (PP) neutrophils (%), PP hematocrit, overall PP viability (%), freeze rate (°C/min), and time from collection to freezing (hr) were shown to contribute to overall PT viability. Each UCB sample was given a calculated "viability prediction" (VP) score based on the influence or impact of each of these variables. This score was compared to the measured PT viability. Variables with a low VP score had correspondingly low PT viability, indicating more overall damage to the cells. The results showed that the higher the VP score, the higher the PT viability. CONCLUSION: These findings provide a framework for identifying those units that are most likely to have a high overall PT viability and hence an increased likelihood of successful engraftment of the CB-sourced stem cells. The VP score could aid in the selection of a donor cord blood unit for transplantation.

Novel relationships between B12, folate and markers of inflammation, oxidative stress and NAD(H) levels, systemically and in the CNS of a healthy human cohort.

OBJECTIVE: To evaluate the relationship between folate, cobalamin (Cbl), and homocysteine (Hcy), and markers of inflammation and oxidative stress within the periphery and central nervous system (CNS) of a healthy human cohort. METHODS: Thirty-five matched cerebrospinal fluid (CSF) and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of Hcy and both plasma and CSF levels of folate, Cbl, nicotinamide adenine dinucleotide (NAD(H)) and markers of inflammation (interleukin-6, IL-6), and oxidative stress (F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and total antioxidant capacity (TAC)) were quantified. RESULTS: In the peripheral circulation, positive associations were observed between plasma folate and Cbl, and plasma TAC (P ≤ 0.01; P ≤ 0.01) and plasma NAD(H) (P ≤ 0.05; P ≤ 0.05) levels, respectively. Plasma folate was inversely associated with plasma Hcy concentrations (P ≤ 0.05); however, no statistically significant relationships were observed between plasma Hcy and plasma markers of inflammation, oxidative stress, or [NAD(H)]. Within the CNS plasma Hcy correlated positively with CSF IL-6 (P ≤ 0.01) and negatively with CSF NAD(H) (P ≤ 0.05) concentrations. An inverse association was observed between CSF folate and CSF levels of IL-6 (P ≤ 0.05). Unexpectedly, a positive association between CSF Cbl and CSF 8-OHdG levels was also found (P ≤ 0.01). DISCUSSION: These results indicate that folate and Cbl concentrations may influence the levels of oxidative damage, inflammation, and NAD(H), both systemically and within the CNS.

Cerebrospinal fluid levels of inflammation, oxidative stress and NAD+ are linked to differences in plasma carotenoid concentrations.

BACKGROUND: The consumption of foods rich in carotenoids that possess significant antioxidant and inflammatory modulating properties has been linked to reduced risk of neuropathology. The objective of this study was to evaluate the relationship between plasma carotenoid concentrations and plasma and cerebrospinal fluid (CSF) markers of inflammation, oxidative stress and nicotinamide adenine dinucleotide (NAD+) in an essentially healthy human cohort. METHODS: Thirty-eight matched CSF and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of carotenoids and both plasma and cerebrospinal fluid (CSF) levels of NAD(H) and markers of inflammation (IL-6, TNF-α) and oxidative stress (F2-isoprostanes, 8-OHdG and total antioxidant capacity) were quantified. RESULTS: The average age of participants was 53 years (SD=20, interquartile range=38). Both α-carotene (P=0.01) and ß-carotene (P<0.001) correlated positively with plasma total antioxidant capacity. A positive correlation was observed between α-carotene and CSF TNF-α levels (P=0.02). ß-cryptoxanthin (P=0.04) and lycopene (P=0.02) inversely correlated with CSF and plasma IL-6 respectively. A positive correlation was also observed between lycopene and both plasma (P<0.001) and CSF (P<0.01) [NAD(H)]. Surprisingly no statistically significant associations were found between the most abundant carotenoids, lutein and zeaxanthin and either plasma or CSF markers of oxidative stress. CONCLUSION: Together these findings suggest that consumption of carotenoids may modulate inflammation and enhance antioxidant defences within both the central nervous system (CNS) and systemic circulation. Increased levels of lycopene also appear to moderate decline in the essential pyridine nucleotide [NAD(H)] in both the plasma and the CSF.

Effect of maternal iron status on the number of CD34+ stem cells harvested from umbilical cord blood.

BACKGROUND: Hematopoietic progenitor cells (HPCs) from umbilical cord blood (UCB) are an alternative source of stem cells. However an adequate number of HPCs must be harvested from each UCB sample to make therapeutic applications possible. This study investigated the impact of selected maternal indices (in particular iron status) on the number of CD34+ cells collected in the UCB. STUDY DESIGN AND METHODS: Blood samples were collected from 91 matched mother and umbilical cord pairs and analyzed for full blood count, iron status, and C-reactive protein. Viable CD34 enumeration was performed on the cord blood samples. RESULTS: Low CD34+ cell counts were associated with higher maternal serum ferritin (SF), older mothers, lower UCB white blood cell count (WCC), lower UCB nucleated red blood cells (NRBCs), and lower birthweight. Maternal SF correlated with maternal variables of iron status and RBC indices, newborn weight, placental weight, and NRBCs/100 WCC. CONCLUSION: This study indicates that lower numbers of CD34+ cells are more likely to occur when collected from mothers with higher SF. This finding suggests that maternal SF and associated iron status play a significant, but as yet undefined, role in the generation of CD34+ cells in UCB.

Mapping NAD(+) metabolism in the brain of ageing Wistar rats: potential targets for influencing brain senescence.

Over the last decade, the importance of NAD(+) has expanded beyond its role as an essential cofactor for energy metabolism. NAD(+) has emerged as a major signalling molecule that serves as the sole substrate for several enzymatic reactions including the DNA repair enzyme, poly(ADP-ribose) polymerase (PARP), NAD-dependent protein deacetylases or CD38, and transcriptional factors by a new class of histone deacetylases known as sirtuins. NAD(+) levels are regulated by the metabolic status and cellular stress caused by oxidative stress and DNA damage. Since a detailed study of NAD(+) metabolism in the healthy ageing mammalian brain is nascent, we examined the effect of ageing on intracellular NAD(+) metabolism in different brain regions in female Wistar rats in young (3 months), middle aged (12 months) and older adults (24 months). Our results are the first to show a significant decline in intracellular NAD(+) levels and NAD:NADH ratio with ageing in the CNS, occurring in parallel to an increase in lipid peroxidation and protein oxidation (o- and m-tyrosine) and a decline in total antioxidant capacity. Hyperphosphorylation of H2AX levels was also observed together with increased PARP-1 and PARP-2 expression, and CD38 activity, concomitantly with reduced NAD(+) and ATP levels and SIRT1 function in the cortex, brainstem, hippocampus and cerebellum. Reduced activity of mitochondrial complex I-IV and impaired maximum mitochondrial respiration rate were also observed in the ageing rat brain. Among the multiple physiological pathways associated with NAD(+) catabolism, our discovery of CD38 as the major regulator of cellular NAD(+) levels in rat neurons indicates that CD38 is a promising therapeutic target for the treatment of age-related neurodegenerative diseases.

Relationship between central and peripheral fatty acids in humans.

BACKGROUND: In recent years the physiological and pathological importance of fatty acids in both the periphery and central nervous system (CNS) has become increasingly apparent. However surprisingly limited research has been conducted comparing the fatty acid composition of central and peripheral lipid stores. METHODS: The present study compared the distribution of polyunsaturated (PUFA), as well as specific saturated (SFA) and monounsaturated (MUFA) fatty acids in the whole blood and cerebrospinal fluid (CSF) of humans. Gas chromatography with flame ionization detection was used to determine the fatty acid profiles of twenty-eight matched CSF and whole blood samples. Multiple linear regression modeling, controlling for age, was used to identify significant relationships. RESULTS: A significant positive relationship was seen between whole blood total omega-3 fatty acids and the CSF omega-3 subfractions, docosapentaenoic acid (DPA) (P = 0.019) and docosahexaenoic acid (DHA) (P = 0.015). A direct association was also observed between the whole blood and CSF omega-6 PUFA, arachidonic acid (AA) (P = 0.045). Interestingly an inverse association between central and peripheral oleic acid was also found (P = 0.045). CONCLUSIONS: These findings indicate a relationship between central and peripheral fatty acids of varying degrees of unsaturation and chain length and support the view that some systemic fatty acids are likely to cross the human blood brain barrier (BBB) and thereby influence central fatty acid concentrations.

Predicting overall viability of cord blood harvests.

BACKGROUND: Cord blood (CB) is a product rich in primitive adult stem cells used in hematopoietic stem cell transplantation. After collection, the CB is transported to a facility where the unit is processed and then frozen up to 48 hours later. These processes can lead to compromised white blood cell (WBC) viability. This study investigates the factors that affect WBC viability before freezing of the cells. STUDY DESIGN AND METHODS: We retrospectively analyzed WBC viability from 9918 CB collections harvested from 2003 to 2010 to determine if collection volume and time to freezing (TTF) had a significant effect on WBC viability. CB was collected in dispersed clinical locations by local staff trained to the same methods. CB was transported to the central lab under controlled conditions for analysis and processing. RESULTS: The collected CB units had a mean volume of 77.1 ± 31.3 mL, mean WBC count of 10.5 × 10(8) ± 5.6 × 10(8) , mean total CD34+ cell count of 4.0 × 10(6) ± 3.7 × 10(6) , and mean WBC viability of 91.7% ± 6.5%. WBC viability was most significantly affected by the volume of CB collected and the TTF. As collection volumes increased, WBC viability increased, with mean viability of 95.0% ± 3.5% in CB collections of more than 120 mL. Decreased viability was associated with volumes of less than 60 mL and TTF of more than 24 hours. From these data we have developed decision tables that estimate WBC viability based on CB volume and TTF. CONCLUSION: This study identifies optimal TTF for different collection volumes to maintain WBC viability of the collected CB.

Exploring the effects of non-medical versus medical approaches to the management of skin aging in women over sixty.

This study was a pilot project, set up to assess ageing skin using a multi-disciplinary approach. The main aim of this study was to evaluate whether the use of more radical ('medical') treatments in the management of skin ageing would bring superior results and ultimately make people look younger, than the use of cosmetics ('non-medical' treatments). A simple post-hoc study design was used, whereby medical treatments varied within the group, all of them completed at least 2 weeks before the start of the study. In addition, it was of interest to assess the suitability of the proposed combination of methods. A total of 21 female participants were recruited for this study: 11 for the non-medical and 10 for the medical group. The multi-disciplinary approach consisted of instrumental measurements, self-assessment, expert assessment by Merz scales and a public perception survey. The majority of nearly 70 sets of instrumental skin data obtained in this study did not differ significantly between the non-medical and the medical group. However, the medical group gave higher self-assessment scores for their faces. The scores for hands were lower than scores for faces by both groups. This was partly supported by instrumental data (lower skin hydration on hands than on the face). The findings of the public perception survey of nine matched pairs of subjects scored the non-medical group as younger looking. Data analysis has shown that the judgement of youthfulness did not depend on either the gender or the age of observers.

Person-to-Person Cancer Transmission via Allogenic Blood Transfusion.

Despite the recognized capability of Circulating Tumor Cells (CTCs) to seed tumors, allogenic blood transfusions are not presently screened for the presence of CTCs. Previous research has examined blood transfusions and the associated risk of cancer recurrence, but not cancer of unknown primary (CUP) occurrence. The Hypothesis explored in this paper proposes that there is potential for cancers to be transmitted from donor-to-patient via CTCs in either blood transfusions or organ transplants or both. This proposed haematogenic tumor transmission will be discussed in relation to two scenarios involving the introduction of donor-derived CTC's from allogeneic blood transfusions into either known cancer surgery patients or into non-cancer patients. The source of CTCs arises either from the donor with a 'clinically dormant cancer' or a 'pre-clinical cancer' existing as yet undiagnosed, in the donor. Given the significant number of allogenic blood transfusions that occur worldwide on a yearly basis, allogenic blood transfusions have the potential to expose a substantial number of non-cancer recipients to the transmission of CTCs and associated tumor risk. This risk is greatly amplified in the low-income nations where the blood collection and processing protocols, including exclusion and screening criteria are less stringent than those in high-income countries.

NADomics: Measuring NAD+ and Related Metabolites Using Liquid Chromatography Mass Spectrometry.

Nicotinamide adenine dinucleotide (NAD+) and its metabolome (NADome) play important roles in preserving cellular homeostasis. Altered levels of the NADome may represent a likely indicator of poor metabolic function. Accurate measurement of the NADome is crucial for biochemical research and developing interventions for ageing and neurodegenerative diseases. In this mini review, traditional methods used to quantify various metabolites in the NADome are discussed. Owing to the auto-oxidation properties of most pyridine nucleotides and their differential chemical stability in various biological matrices, accurate assessment of the concentrations of the NADome is an analytical challenge. Recent liquid chromatography mass spectrometry (LC-MS) techniques which overcome some of these technical challenges for quantitative assessment of the NADome in the blood, CSF, and urine are described. Specialised HPLC-UV, NMR, capillary zone electrophoresis, or colorimetric enzymatic assays are inexpensive and readily available in most laboratories but lack the required specificity and sensitivity for quantification of human biological samples. LC-MS represents an alternative means of quantifying the concentrations of the NADome in clinically relevant biological specimens after careful consideration of analyte extraction procedures, selection of internal standards, analyte stability, and LC assays. LC-MS represents a rapid, robust, simple, and reliable assay for the measurement of the NADome between control and test samples, and for identifying biological correlations between the NADome and various biochemical processes and testing the efficacy of strategies aimed at raising NAD+ levels during physiological ageing and disease states.

Cardiovascular Disease Risk Factors Profile Among Australian Vegetarian and Nonvegetarian Teenagers.

Atherosclerosis develops over a long period of time and often begins in childhood. The goal of this study was to make a cross-sectional assessment of the pattern of cardiovascular disease risk factors among Australian vegetarian (n = 49) and nonvegetarian (n = 639) 14- to 17-year-old participants from New South Wales, Australia. Vegetarians had statistically significant lower mean total (4.05 vs 4.4 mmol/L;P < .001) and low-density lipoprotein (LDL) cholesterol (2.18 vs 2.55 mmol/L; P < .001) and lower incidence of abnormal total and LDL cholesterol (31.1% vs 46.2%, P = .036, having total cholesterol ≥4.4 mmol/L and 13.3% vs 29.6%, P = .021, having LDL cholesterol ≥2.84 mmol/L). Vegetarians had a higher diastolic BP (72.0 vs 69.7 mm Hg; P = .038). No statistically significant difference was found in other risk factors including high-density lipoprotein cholesterol (P = .83), triglycerides (P = .601), systolic blood pressure (P = .727), body mass index (P = .159), plasma glucose (P = .09), C-reactive protein (P = .527), or homocysteine (P = .45). The prevalence rate with 3 or more risk factors was 12.2% among vegetarians and 13.9% among nonvegetarians (P = .156). The high percentage of abnormal total cholesterol in both diet groups and, in addition, LDL cholesterol in nonvegetarians is a cause of concern and underlines the need for lifestyle change.

The Potential Benefit of Monitoring Oxidative Stress and Inflammation in the Prevention of Non-Communicable Diseases (NCDs).

The significant increase in worldwide morbidity and mortality from non-communicable diseases (NCDs) indicates that the efficacy of existing strategies addressing this crisis may need improvement. Early identification of the metabolic irregularities associated with the disease process may be a key to developing early intervention strategies. Unhealthy lifestyle behaviours are well established drivers of the development of several NCDs, but the impact of such behaviours on health can vary considerably between individuals. How can it be determined if an individual's unique set of lifestyle behaviours is producing disease? Accumulating evidence suggests that lifestyle-associated activation of oxidative and inflammatory processes is primary driver of the cell and tissue damage which underpins the development of NCDs. However, the benefit of monitoring subclinical inflammation and oxidative activity has not yet been established. After reviewing relevant studies in this context, we suggest that quantification of oxidative stress and inflammatory biomarkers during the disease-free prodromal stage of NCD development may have clinical relevance as a timely indicator of the presence of subclinical metabolic changes, in the individual, portending the development of disease. Monitoring markers of oxidative and inflammatory activity may therefore enable earlier and more efficient strategies to both prevent NCD development and/or monitor the effectiveness of treatment.