Early microstructural white matter changes in patients with HIV: A diffusion tensor imaging study

Background: Previous studies have reported white matter (WM) brain alterations in asymptomatic patients with human immunodeficiency virus (HIV). Methods: We compared diffusion tensor imaging (DTI) derived WM fractional anisotropy (FA) between HIV-patients with and without mild macroscopic brain lesions determined using standard magnetic resonance imaging (MRI). We furthermore investigated whether WM alterations co-occurred with neurocognitive deficits and depression. We performed structural MRI and DTI for 19 patients and 19 age-matched healthy controls. Regionally-specific WM integrity was investigated using voxel-based statistics of whole-brain FA maps and region-of-interest analysis. Each patient underwent laboratory and neuropsychological tests. Results: Structural MRI revealed no lesions in twelve (HIV-MRN) and unspecific mild macrostructural lesions in seven patients (HIV-MRL). Both analyses revealed widespread FA-alterations in all patients. Patients with HIV-MRL had FA-alterations primarily adjacent to the observed lesions and, whilst reduced in extent, patients with HIV-MRN also exhibited FA-alterations in similar regions. Patients with evidence of depression showed FA-increase in the ventral tegmental area, pallidum and nucleus accumbens in both hemispheres, and patients with evidence of HIV-associated neurocognitive disorder showed widespread FA-reduction. Conclusion: These results show that patients with HIV-MRN have evidence of FA-alterations in similar regions that are lesioned in HIV-MRL patients, suggesting common neuropathological processes. Furthermore, they suggest a biological rather than a reactive origin of depression in HIV-patients

Single and repeated moderate consumption of native or dealcoholized red wine show different effects on antioxidant parameters in blood and DNA strand breaks in peripheral leukocytes in healthy volunteers: a randomized controlled trial [ISRCTN68505294]

BACKGROUND: Red wine (RW) is rich in antioxidant polyphenols that might protect from oxidative stress related diseases, such as cardiovascular disease and cancer. Antioxidant effects after single ingestion of RW or dealcoholized RW (DRW) have been observed in several studies, but results after regular consumption are contradictory. Thus, we examined if single or repeated consumption of moderate amounts of RW or DRW exert antioxidant activity in vivo. METHODS: Total phenolic content and concentration of other antioxidants in plasma/serum, total antioxidant capacity (TEAC) in plasma as well as DNA strand breaks in peripheral leukocytes were measured in healthy non-smokers A) before, 90 and 360 min after ingestion of one glass of RW, DRW or water; B) before and after consumption of one glass of RW or DRW daily for 6 weeks. DNA strand breaks (SB) were determined by single cell gel electrophoresis (Comet Assay) in untreated cells and after induction of oxidative stress ex vivo with H(2)O(2 )(300 μM, 20 min). RESULTS: Both RW and DRW transiently increased total phenolic content in plasma after single consumption, but only RW lead to a sustained increase if consumed regularly. Plasma antioxidant capacity was not affected by single or regular consumption of RW or DRW. Effects of RW and DRW on DNA SB were conflicting. DNA strand breaks in untreated cells increased after a single dose of RW and DRW, whereas H(2)O(2 )induced SB were reduced after DRW. In contrast, regular RW consumption reduced SB in untreated cells but did not affect H(2)O(2 )induced SB. CONCLUSION: The results suggest that consumption of both RW and DRW leads to an accumulation of phenolic compounds in plasma without increasing plasma antioxidant capacity. Red wine and DRW seem to affect the occurrence of DNA strand breaks, but this cannot be referred to antioxidant effects

Assessment of parenteral nutrition prescription in Canadian acute care settings

Background: Parenteral nutrition (PN) prescription can be challenging in patients with complex conditions and has potential complications. Objective: To assess PN prescription, monitoring, and PN-related complications in a Canadian acute care setting. Methods: This was a prospective cohort study in which patients receiving PN were assessed by an auditor for nutritional status, PN-related prescription, monitoring, and complications. In addition, length of stay and mortality were recorded. Results: 147 patients (mean ± SD 56.1 ± 16.4 y) with complex diseases (Charlson comorbidity index, median [p25–p75] 2 [1–4]) were enrolled. Before starting PN, 18.6%, 63.9%, and 17.5% of patients were classified as subjective global assessment A, B, and C, respectively. Body mass index remained unchanged during the period on PN. On average, 89% and 73% of patients received <90% of their energy and protein requirements, respectively, but 65% received oral or enteral nutrition at some point during PN. The average daily energy provided by PN increased and stabilized on day 10, reaching 87.2 ± 20.1% of the requirements. Line sepsis (6.8% of patients) and hyperglycemia (6.9%) were the most common complications. The overall mortality was 15.6%. For those alive, length of stay was 30 (range: 4–268) d. PN was discontinued because of transitioning to an oral diet (56.6%), enteral nutrition (17.6%), home PN (14.7%), palliative care (5.1%), death (4.4%), or other (1.5%). Conclusion: Most patients were malnourished at the start of PN. Energy and protein provided from PN were less than requirements, and the goals were reached with delay. Mortality was high, possibly as a result of complex diseases.Baxter Corporation Canad

Safety and Suitability of an Infant Formula Manufactured from Extensively Hydrolysed Protein in Healthy Term Infants

We aimed to demonstrate that healthy term infants experience noninferior growth with infant formula manufactured from extensively hydrolysed whey protein (eHF) compared to intact cow’s milk protein (control formula, CF). This prospective, randomised, double-blind, parallel-group, controlled, multicentre trial included healthy term infants who were exclusively formula-fed. Infants ≤ 25 days of age received eHF or CF for at least three months up to 120 days of age, with a follow-up until 180 days of age. A reference group included exclusively breastfed infants (BF). Of 318 infants randomised, 297 (148 CF, 149 eHF) completed the study per protocol. Weight gain up to 120 days of age was noninferior (margin −3.0 g/day) in eHF (28.95 (95% CI: 27.21; 30.68) g/day) compared to CF (28.85 (95% CI: 27.10; 30.61) g/day) with a difference in means of 0.09 g/day and a lower limit of the one-sided 97.5% CI of −0.86 g/day (p < 0.0001 for noninferiority testing). Weight gain remained comparable during follow-up. Further anthropometric parameters did not differ between the infant formula groups throughout the study. Growth was comparable in BF. No relevant safety issues were observed. To conclude, eHF meets infant requirements for adequate growth during the first six months of life and can be considered safe and suitable

Single and repeated moderate consumption of native or dealcoholized red wine show different effects on antioxidant parameters in blood and DNA strand breaks in peripheral leukocytes in healthy volunteers: a randomized controlled trial [ISRCTN68505294]

Abstract Background Red wine (RW) is rich in antioxidant polyphenols that might protect from oxidative stress related diseases, such as cardiovascular disease and cancer. Antioxidant effects after single ingestion of RW or dealcoholized RW (DRW) have been observed in several studies, but results after regular consumption are contradictory. Thus, we examined if single or repeated consumption of moderate amounts of RW or DRW exert antioxidant activity in vivo. Methods Total phenolic content and concentration of other antioxidants in plasma/serum, total antioxidant capacity (TEAC) in plasma as well as DNA strand breaks in peripheral leukocytes were measured in healthy non-smokers A) before, 90 and 360 min after ingestion of one glass of RW, DRW or water; B) before and after consumption of one glass of RW or DRW daily for 6 weeks. DNA strand breaks (SB) were determined by single cell gel electrophoresis (Comet Assay) in untreated cells and after induction of oxidative stress ex vivo with H2O2 (300 μM, 20 min). Results Both RW and DRW transiently increased total phenolic content in plasma after single consumption, but only RW lead to a sustained increase if consumed regularly. Plasma antioxidant capacity was not affected by single or regular consumption of RW or DRW. Effects of RW and DRW on DNA SB were conflicting. DNA strand breaks in untreated cells increased after a single dose of RW and DRW, whereas H2O2 induced SB were reduced after DRW. In contrast, regular RW consumption reduced SB in untreated cells but did not affect H2O2 induced SB. Conclusion The results suggest that consumption of both RW and DRW leads to an accumulation of phenolic compounds in plasma without increasing plasma antioxidant capacity. Red wine and DRW seem to affect the occurrence of DNA strand breaks, but this cannot be referred to antioxidant effects.</p

Intestinal Microbiota in Patients with Non-Alcoholic Fatty Liver Disease

Despite evidence that the intestinal microbiota (IM) is involved in the pathogenesis of obesity, the IM composition of patients with non-alcoholic fatty liver disease (NAFLD) has not been well characterized. This prospective, cross-sectional study was aimed at identifying differences in IM between adults with biopsy-proven NAFLD (simple steatosis [SS] or non-alcoholic steatohepatitis [NASH]) and living liver donors as healthy controls (HC). Fifty subjects were included: 11 SS, 22 NASH and 17 HC. One stool sample was collected from each participant. Quantitative real-time polymerase chain reaction was used to measure total bacterial counts, Bacteroides/Prevotella (here on referred to as Bacteroidetes), C. leptum, C. coccoides, bifidobacteria, E. coli and Archaea in stool. Clinical and laboratory data, food-records, and activity logs were collected. Patients with NASH had a lower percentage of Bacteroidetes (Bacteroidetes to total bacteria counts) compared to both SS and HC (p=0.006) and higher fecal C. coccoides compared to those with SS (p=0.04). There were no differences in the remaining microorganisms. As body mass index (BMI) and dietary fat intake differed between the groups (p<0.05), we performed linear regression adjusting for these variables. The difference in C. coccoides was no longer significant after adjusting for BMI and fat intake. However, there continued to be a significant association between the presence of NASH and lower percentage Bacteroidetes even after adjusting for these variables (p= 0.002; 95% CI= -0.06 to -0.02). Conclusion: There is an inverse and diet-/BMI-independent association between the presence of NASH and percentage Bacteroidetes in the stool, suggesting that the IM may play a role in the development of NAFLD.Canadian Institutes of Health Research (Grants NMD-86922, MOP-89705, MOP-123459

Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) is a chronic liver disease commonly associated with hepatic fibrosis. NASH patients have an increased risk for hepatocellular carcinoma (HCC). An altered retinol metabolism is one of the pathways involved in the process of hepatic fibrosis, and enzymes involved in retinol metabolism have been associated with HCC. We aimed to determine the association between plasma retinol levels and hepatic expression of genes related to retinol metabolism, as well as to assess the hepatic expression of transcription factors regulated by retinoic acid in patients with NAFLD. Cross-sectional study where hepatic gene expression (Illumina microarray) and plasma retinol levels (HPLC) were measured in 17 patients with simple steatosis (SS), 15 with NASH, and 22 living liver donors (LD) as controls. Plasma retinol levels were higher in SS (1.53 ± 0.44 μmol/L) and NASH (1.51 ± 0.56 μmol/L) compared to LD (1.21 ± 0.38 μmol/L; p<0.05). AKR1B10 was highly overexpressed in NASH compared to SS (+6.2-fold) and LD (+9.9-fold; p = 4.89E-11). Retinaldehyde dehydrogenase 1 family, member A2 (ALDH1A2) and retinaldehyde dehydrogenase 1 family, member A3 (ALDH1A3), key enzymes for retinoic acid synthesis, were underexpressed in SS (-1.48 and -2.3-fold, respectively) and NASH (-1.47 and -2.6-fold, respectively) versus LD. In NASH, hepatic ALDH1A2 and ALDH1A3 were underexpressed and inversely correlated with plasma retinol levels, which may reduce retinoic acid in the liver. This, in addition to changes in expression of other genes involved in retinol metabolism, suggests a role for altered retinol homeostasis in NASH