Four-week short chain fructo-oligosaccharides ingestion leads to increasing fecal bifidobacteria and cholesterol excretion in healthy elderly volunteers

<p>Abstract</p> <p>Background</p> <p>Short-chain fructo-oligosaccharides (scFOS) are increasingly used in human diet for their prebiotic properties. We aimed at investigating the effects of scFOS ingestion on the colonic microflora and oro-fecal transit time in elderly healthy humans.</p> <p>Methods</p> <p>Stools composition, oro-fecal transit time, and clinical tolerance were evaluated in 12 healthy volunteers, aged 69 ± 2 yrs, in three consecutive periods: basal period (2 weeks), scFOS (Actilight^®) ingestion period (8 g/d for 4 weeks) and follow-up period (4 weeks). Two-way ANOVA, with time and treatment as factors, was used to compare the main outcome measures between the three periods.</p> <p>Results</p> <p>Fecal bifidobacteria counts were significantly increased during the scFOS period (9.17 ± 0.17 log cfu/g vs 8.52 ± 0.26 log cfu/g during the basal period) and returned to their initial values at the end of follow-up (8.37 ± 0.21 log cfu/g; P < 0.05). Fecal cholesterol concentration increased during the scFOS period (8.18 ± 2.37 mg/g dry matter vs 2.81 ± 0.94 mg/g dry matter during the basal period) and returned to the baseline value at the end of follow-up (2.87 ± 0.44 mg/g dry matter; P < 0.05). Fecal pH tended to decrease during scFOS ingestion and follow-up periods compared to the basal period (P = 0.06). Fecal bile acids, stool weight, water percentage, and oro-fecal transit time did not change throughout the study. Excess flatus and bloating were significantly more frequent during scFOS ingestion when compared to the basal period (P < 0.05), but the intensity of these symptoms was very mild.</p> <p>Conclusion</p> <p>Four-week 8 g/d scFOS ingestion is well tolerated and leads to a significant increase in fecal bifidobacteria in healthy elderly subjects. Whether the change in cholesterol metabolism found in our study could exert a beneficial action warrants further studies.</p

T cell lymphoproliferative disorders associated with anti-tumor necrosis factor alpha antibody therapy for ulcerative colitis: literature summary

The enhanced risk of development of lymphoproliferative disorders in patients with inflammatory bowel disease has been attributed to immunosuppressive/immunomodulatory therapies. Infliximab is a chimeric monoclonal immunoglobulin G1 antibody directed against tumor necrosis factor alpha (TNF-α) that was approved by the Food and Drug Administration (FDA) in 1998 as an effective therapeutic agent against inflammatory bowel disease. Malignant lymphomas of both B and T cell lineage have been described in patients undergoing therapy involving TNF-α blockade. To date, eight cases of Epstein–Barr virus (EBV)-negative hepatosplenic T cell lymphoma associated with infliximab have been reported to the FDA’s Adverse Event Reporting System, as well as several other T cell lymphoproliferative disorders with aggressive clinical outcomes. We present the histologic, immunophenotypic, and molecular features of a T cell lymphoproliferative disorder involving the axillary lymph node of a 33-year-old male following infliximab treatment for ulcerative colitis. These EBV-negative lymphomas suggest that lymphoproliferative disorders following infliximab treatment for inflammatory bowel disease may involve EBV-independent immune dysregulation. The spectrum of lymphoproliferative disorders associated with infliximab and the potential mechanisms by which they occur are discussed

Effect of the consumption of a fermented dairy product containing Bifidobacterium lactis DN-173 010 on constipation in childhood: a multicentre randomised controlled trial (NTRTC: 1571)

<p>Abstract</p> <p>Background</p> <p>Constipation is a frustrating symptom affecting 3% of children worldwide. Randomised controlled trials show that both polyethylene glycol and lactulose are effective in increasing defecation frequency in children with constipation. However, in 30–50%, these children reported abdominal pain, bloating, flatulence, diarrhoea, nausea and bad taste of the medication. Two recent studies have shown that the fermented dairy product containing <it>Bifidobacterium lactis </it>strain DN-173 010 is effective in increasing stool frequency in constipation-predominant irritable bowel syndrome patients with a defecation frequency < 3/week and in constipated women with a defecation frequency < 3/week. Goal of this study is to determine whether this fermented dairy product is effective in the treatment of constipated children with a defecation frequency < 3/week.</p> <p>Methods/design</p> <p>It is a two nation (The Netherlands and Poland) double-blind, placebo-controlled randomised multicentre trial in which 160 constipated children (age 3–16 years) with a defecation frequency <3/week will be randomly allocated to consume a fermented dairy product containing <it>Bifidobacterium lactis </it>DN-173 010 or a control product, twice a day, for 3 weeks. During the study all children are instructed to try to defecate on the toilet for 5–10 minutes after each meal (3 times a day) and daily complete a standardized bowel diary. Primary endpoint is stool frequency. Secondary endpoints are stool consistency, faecal incontinence frequency, pain during defecation, digestive symptoms (abdominal pain, flatulence), adverse effects (nausea, diarrhoea, bad taste) and intake of rescue medication (Bisacodyl). Rate of success and rate of responders are also evaluated, with success defined as ≥ 3 bowel movements per week and ≤1 faecal incontinence episode over the last 2 weeks of product consumption and responder defined as a subject reporting a stool frequency ≥ 3 on the last week of product consumption. To demonstrate that the success percentage in the intervention group will be 35% and the success percentage in the control group (acidified milk without ferments, toilet training, bowel diary) will be 15%, with alpha 0.05 and power 80%, a total sample size of 160 patients was calculated.</p> <p>Conclusion</p> <p>This study is aimed to show that the fermented dairy product containing <it>Bifidobacterium lactis </it>strain DN-173 010 is effective in increasing stool frequency after 3 weeks of product consumption in children with functional constipation and a defecation frequency < 3/week.</p

Effect of oral lactulose on clinical and immunohistochemical parameters in patients with inflammatory bowel disease: a pilot study

<p>Abstract</p> <p>Background</p> <p>The prebiotic potential of lactulose is well established and preclinical studies demonstrated a protective effect of lactulose in murine models of colitis. The aim of the present study was to investigate the clinical and histological efficacy of lactulose in patients with inflammatory bowel disease (IBD), for which probiotic therapy yielded promising results.</p> <p>Methods</p> <p>Patients were treated with standard medication alone or combined with 10 g lactulose daily as adjuvant therapy for 4 months. Clinical efficacy of treatment was assessed using clinical activity indices, a quality of life index (IBDQ), endoscopic scores, defecation frequency and monitoring corticosteroid medication. Orsomucoid, alpha1-antitrypsin and other laboratory parameters were determined. In addition, in some participants colonic biopsies were analyzed with haematoxylin-eosin staining or with antibodies against HLA-DR, CD68, IgA and CD3, and evaluated systematically. All measurements were performed both at enrolment and at the end of the trial.</p> <p>Results</p> <p>14 patients presenting ulcerative colitis (UC) and 17 patients presenting Crohn's disease (CD), most of them in a clinically active state, were enrolled in this pilot study. After 4 month no significant improvement of clinical activity index, endoscopic score or immunohistochemical parameters was observed in CD or UC patients receiving lactulose in comparison to the control group. However, significant improvement of quality of life was observed in UC patients receiving lactulose compared to the control group (p = 0.04).</p> <p>Conclusion</p> <p>The findings of the present pilot study indicate that oral lactulose has no beneficial effects in IBD patients in particular with regard to clinical activity, endoscopic score or immunohistochemical parameters. The importance of the beneficial effect of lactulose in UC patients regarding the quality of life needs further evaluation in larger controlled clinical trials.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN92101486</p

Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: A prospective multicohort study of the ABIRISK consortium

BACKGROUND: Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited. METHODS AND FINDINGS: The European consortium ABIRISK (Anti-Biopharmaceutical Immunization: prediction and analysis of clinical relevance to minimize the RISK) conducted a clinical and genomic multicohort prospective study of 560 patients with multiple sclerosis (MS, n = 147), rheumatoid arthritis (RA, n = 229), Crohn's disease (n = 148), or ulcerative colitis (n = 36) treated with 8 different biopharmaceuticals (etanercept, n = 84; infliximab, n = 101; adalimumab, n = 153; interferon [IFN]-beta-1a intramuscularly [IM], n = 38; IFN-beta-1a subcutaneously [SC], n = 68; IFN-beta-1b SC, n = 41; rituximab, n = 31; tocilizumab, n = 44) and followed during the first 12 months of therapy for time to ADA development. From the bioclinical data collected, we explored the relationships between patient-related factors and the occurrence of ADAs. Both baseline and time-dependent factors such as concomitant medications were analyzed using Cox proportional hazard regression models. Mean age and disease duration were 35.1 and 0.85 years, respectively, for MS; 54.2 and 3.17 years for RA; and 36.9 and 3.69 years for inflammatory bowel diseases (IBDs). In a multivariate Cox regression model including each of the clinical and genetic factors mentioned hereafter, among the clinical factors, immunosuppressants (adjusted hazard ratio [aHR] = 0.408 [95% confidence interval (CI) 0.253-0.657], p < 0.001) and antibiotics (aHR = 0.121 [0.0437-0.333], p < 0.0001) were independently negatively associated with time to ADA development, whereas infections during the study (aHR = 2.757 [1.616-4.704], p < 0.001) and tobacco smoking (aHR = 2.150 [1.319-3.503], p < 0.01) were positively associated. 351,824 Single-Nucleotide Polymorphisms (SNPs) and 38 imputed Human Leukocyte Antigen (HLA) alleles were analyzed through a genome-wide association study. We found that the HLA-DQA1*05 allele significantly increased the rate of immunogenicity (aHR = 3.9 [1.923-5.976], p < 0.0001 for the homozygotes). Among the 6 genetic variants selected at a 20% false discovery rate (FDR) threshold, the minor allele of rs10508884, which is situated in an intron of the CXCL12 gene, increased the rate of immunogenicity (aHR = 3.804 [2.139-6.764], p < 1 × 10-5 for patients homozygous for the minor allele) and was chosen for validation through a CXCL12 protein enzyme-linked immunosorbent assay (ELISA) on patient serum at baseline before therapy start. CXCL12 protein levels were higher for patients homozygous for the minor allele carrying higher ADA risk (mean: 2,693 pg/ml) than for the other genotypes (mean: 2,317 pg/ml; p = 0.014), and patients with CXCL12 levels above the median in serum were more prone to develop ADAs (aHR = 2.329 [1.106-4.90], p = 0.026). A limitation of the study is the lack of replication; therefore, other studies are required to confirm our findings. CONCLUSION: In our study, we found that immunosuppressants and antibiotics were associated with decreased risk of ADA development, whereas tobacco smoking and infections during the study were associated with increased risk. We found that the HLA-DQA1*05 allele was associated with an increased rate of immunogenicity. Moreover, our results suggest a relationship between CXCL12 production and ADA development independent of the disease, which is consistent with its known function in affinity maturation of antibodies and plasma cell survival. Our findings may help physicians in the management of patients receiving biotherapies

Sexual (Dis)satisfaction and Its Contributors Among People Living with HIV Infection in Sweden

Earlier research reports lower sexual satisfaction among people living with HIV (PLHIV) compared to HIV-negative persons. A number of psychosocial factors directly associated with sexual dissatisfaction have been identified. Little is known about sexual satisfaction and their contributors among PLHIV in Sweden. The aim of this study was to examine direct and indirect effects of variables within sociodemographic, clinical HIV-related, psychological, and sexual domains on sexual(dis)satisfaction among PLHIV in Sweden. Data for this study was derived from a national representative, anonymous survey among PLHIV conducted in 2014 (n=1096). Statistical analysis included four steps: descriptive analyses, identification of variables associated with sexual (dis)satisfaction, identification of variables associated with those contributors of sexual (dis)satisfaction, and a path model integrating all these analyses. A total of 49% of participants reported being sexually dissatisfied and no significant differences were observed when non-heterosexual men, heterosexual men and women were compared. Among women, a negative change in sex life after HIV diagnosis and distress with orgasmic difficulties were directly associated with sexual dissatisfaction. For men, hopelessness, high HIV stigma, sexual inactivity in the last 6 months, and a negative change in sex life after HIV diagnosis were directly associated with sexual dissatisfaction. Path analyses showed in both men and women significant indirect association between not being involved in an intimate relationship, lower self-reported CD4 cell counts, and perceiving obligation to disclose HIV status to sexual partners as a barrier to look for a long-term partner and sexual dissatisfaction. Our results show that despite good treatment outcomes, the HIV diagnosis has a negative bearing on sexual satisfaction. The need for gender-tailored interventions and clinical implications of these findings are discussed

An empirical analysis of the determinants of mobile instant messaging appropriation in university learning

Published ArticleResearch on technology adoption often profiles device usability (such as perceived usefulness) and user dispositions (such as perceived ease of use) as the prime determinants of effective technology adoption. Since any process of technology adoption cannot be conceived out of its situated contexts, this paper argues that any pre-occupation with technology acceptance from the perspective of device usability and user dispositions potentially negates enabling contexts that make successful adoption a reality. Contributing to contemporary debates on technology adoption, this study presents flexible mobile learning contexts comprising cost (device cost and communication cost), device capabilities (portability, collaborative capabilities), and learner traits (learner control) as antecedents that enable the sustainable uptake of emerging technologies. To explore the acceptance and capacity of mobile instant messaging systems to improve student performance, the study draws on these antecedents, develops a factor model and empirically tests it on tertiary students at a South African University of Technology. The study involved 223 national diploma and bachelor’s degree students and employed partial least squares for statistical analysis. Overall, the proposed model displayed a good fit with the data and rendered satisfactory explanatory power for students’ acceptance of mobile learning. Findings suggest that device portability, communication cost, collaborative capabilities of device and learner control are the main drivers of flexible learning in mobile environments. Flexible learning context facilitated by learner control was found to have a positive influence on attitude towards mobile learning and exhibited the highest path coefficient of the overall model. The study implication is that educators need to create varied learning opportunities that leverage learner control of learning in mobile learning systems to enhance flexible mobile learning. The study also confirmed the statistical significance of the original Technology Acceptance Model constructs

Discrimination against HIV-Infected People and the Spread of HIV: Some Evidence from France

BACKGROUND: Many people living with HIV/AIDS (PLWHA) suffer from stigma and discrimination. There is an ongoing debate, however, about whether stigma, fear and discrimination actually fuel the persisting spread of HIV, or slow it down by reducing contacts between the whole population and high-risk minorities. To contribute to this debate, we analysed the relationship between perceived discrimination and unsafe sex in a large sample of French PLWHAs. METHODOLOGY/PRINCIPAL FINDINGS: In 2003, we conducted a national cross-sectional survey among a random sample of HIV-infected patients. The analysis was restricted to sexually active respondents (N = 2,136). Unsafe sex was defined as sexual intercourse without a condom with a seronegative/unknown serostatus partner during the prior 12 months. Separate analyses were performed for each transmission group (injecting drug use (IDU), homosexual contact, heterosexual contact). Overall, 24% of respondents reported experiences of discrimination in their close social environment (relatives, friends and colleagues) and 18% reported unsafe sex during the previous 12 months. Both prevalences were higher in the IDU group (32% for perceived discrimination, 23% for unsafe sex). In multivariate analyses, experience of discrimination in the close social environment was associated with an increase in unsafe sex for both PLWHAs infected through IDU and heterosexual contact (OR = 1.65 and 1.80 respectively). CONCLUSIONS: Our study clearly confirms a relationship between discrimination and unsafe sex among PLWHAs infected through either IDU or heterosexual contact. This relationship was especially strong in the heterosexual group that has become the main vector of HIV transmission in France, and who is the more likely of sexual mixing with the general population. These results seriously question the hypothesis that HIV-stigma has no effect or could even reduce the infection spread of HIV