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Gut-microbiome-related LCT genotype and 2-year changes in body composition and fat distribution: the POUNDS Lost Trial.
Heianza, Y, Sun, D, Ma, W, Zheng, Y, Champagne, CM, Bray, GA, Sacks, FM, Qi, L
International journal of obesity (2005). 2018;(9):1565-1573
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Abstract
BACKGROUND/OBJECTIVES Gut microbiome regulates host energy metabolism and adiposity. A recent study identified a genome-wide significant variant in the lactase (LCT) gene that determines gut-microbiome abundance. We investigated whether the LCT variant influenced long-term changes in adiposity among overweight and obese individuals. SUBJECTS/METHODS We included 583 whites with LCT variant rs4988235 (G allele as Bifidobacterium-abundance-increasing allele) who were randomly assigned to one of four weight-loss diets varying in macronutrient contents. Two-year changes in adiposity measures were assessed according to the LCT genotype and weight-loss diets. RESULTS We observed a significant interaction between the LCT genotype and dietary protein intake on changes in whole body total fat mass %, trunk fat %, superficial adipose tissue mass (SAT), visceral adipose tissue mass (VAT), and total adipose tissue mass (TAT) (Pinteraction < 0.05 for all). In response to high-protein diet, carrying the G allele of LCT variant rs4988235 was associated with greater reduction of whole body total fat mass % (β [SE] -0.9 [0.43], P = 0.04), trunk fat % (-1.06 [0.58], P = 0.07), SAT (-0.89 [0.42], P = 0.04), VAT (-0.63 [0.27], P = 0.03), and TAT (-1.69 [0.76], P = 0.03). Conversely, increasing numbers of the G allele tended to be related to less reduction of these outcomes in response to low-protein diet. CONCLUSIONS Long-term improvement of body fat composition and distribution was significantly influenced by the Bifidobacterium-related LCT genotype and dietary protein intake. Overweight and obese individuals with the G allele of LCT variant rs4988235 may benefit improving adiposity by eating a low-calorie, high-protein diet.
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Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study.
Togashi, T, Mitsuya, N, Kogawara, O, Sumino, S, Takanami, Y, Sugizaki, K
Vaccine. 2016;(38):4635-4641
Abstract
BACKGROUND Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged <1year. In Japan, PRP conjugated to tetanus toxoid (PRP-T) vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. METHODS We compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria-tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series. RESULTS Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (p<0.0001). Furthermore, the "short-term seroprotection rate" (anti-PRP antibody titer ⩾0.15μg/mL) before booster vaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. CONCLUSION The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns. CLINICAL TRIAL REGISTRY Registered on ClinicalTrials.gov: NCT01379846.
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Effect of isoniazid on antigen-specific interferon-γ secretion in latent tuberculosis.
Torres, M, García-García, L, Cruz-Hervert, P, Guio, H, Carranza, C, Ferreyra-Reyes, L, Canizales, S, Molina, S, Ferreira-Guerrero, E, Téllez, N, et al
The European respiratory journal. 2015;(2):473-82
Abstract
Treatment of persons with latent tuberculosis (TB) infection at greatest risk of reactivation is an important component of TB control and elimination strategies. Biomarkers evaluating the effectiveness of treatment of latent TB infection have not yet been identified. This information would enhance control efforts and assist the evaluation of new treatment regimes. We designed a two-group, two-arm, randomised clinical study of tuberculin skin test-positive participants: 26 with documented contact with TB patients and 34 with non-documented contact. Participants in each group were randomly assigned to the immediate- or deferred-isoniazid treatment arms. Assays of in vitro interferon (IFN)-γ secretion in response to recombinant Rv1737 and overlapping synthetic peptide pools from various groups of immunodominant proteins were performed. During isoniazid therapy, a significant increase from baseline in the proportion of IFN-γ responders to the 10-kDa culture filtrate protein, Rv2031, Rv0849, Rv1986, Rv2659c, Rv2693c and the recombinant Rv1737 protein was observed (p⩽0.05). The peptide pool of Rv0849 and Rv1737 recombinant proteins induced the highest percentage of IFN-γ responders after isoniazid therapy. The in vitro IFN-γ responses to these proteins might represent useful markers to evaluate changes associated with treatment of latent TB infection.
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Helicobacter pylori seropositivity and risk of lung cancer.
Koshiol, J, Flores, R, Lam, TK, Taylor, PR, Weinstein, SJ, Virtamo, J, Albanes, D, Perez-Perez, G, Caporaso, NE, Blaser, MJ
PloS one. 2012;(2):e32106
Abstract
Lung cancer is the leading cause of cancer mortality worldwide. Helicobacter pylori (H. pylori) is a risk factor for distal stomach cancer, and a few small studies have suggested that H. pylori may be a potential risk factor for lung cancer. To test this hypothesis, we conducted a study of 350 lung adenocarcinoma cases, 350 squamous cell carcinoma cases, and 700 controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) cohort of male Finnish smokers. Controls were one-to-one matched by age and date of baseline serum draw. Using enzyme-linked immunosorbent assays to detect immunoglobulin G antibodies against H. pylori whole-cell and cytotoxin-associated gene (CagA) antigens, we calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between H. pylori seropositivity and lung cancer risk using conditional logistic regression. H. pylori seropositivity was detected in 79.7% of cases and 78.5% of controls. After adjusting for pack-years and cigarettes smoked per day, H. pylori seropositivity was not associated with either adenocarcinoma (OR: 1.1, 95% CI: 0.75-1.6) or squamous cell carcinoma (OR: 1.1, 95% CI: 0.77-1.7). Results were similar for CagA-negative and CagA-positive H. pylori seropositivity. Despite earlier small studies suggesting that H. pylori may contribute to lung carcinogenesis, H. pylori seropositivity does not appear to be associated with lung cancer.
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A phase 1, randomized, open-label, active-controlled trial to assess the safety of a meningococcal serogroup B bivalent rLP2086 vaccine in healthy adults.
Sheldon, EA, Schwartz, H, Jiang, Q, Giardina, PC, Perez, JL
Human vaccines & immunotherapeutics. 2012;(7):888-95
Abstract
Neisseria meningitidis serogroup B (MnB) is a significant cause of invasive meningococcal disease, but no broadly protective vaccine is yet approved. We assessed the safety and immunogenicity of a bivalent MnB vaccine composed of lipidated subfamily A and B variants of recombinant LP2086 (rLP2086, also known as factor H binding protein, fHBP). Forty-eight adults, ages 18-40 y, were randomized to receive 60, 120 or 200 μg of the bivalent rLP2086 vaccine or control at 0, 2 and 6 mo. Immunogenicity was assessed by rLP2086-specific immunoglobulin G (IgG) geometric mean titers for subfamily A and B proteins. Safety was determined by laboratory assessments of blood and urine and by reporting of solicited and unsolicited adverse events (AEs). The bivalent rLP2086 vaccine elicited high IgG titers following the second and third vaccination at all dose levels. In each of the four study arms, 11 of the 12 participating subjects reported ≥ 1 AE, and no serious AEs were reported. Local and systemic reactions were mainly mild to moderate. Laboratory abnormalities (including increased sodium, decreased neutrophils, and proteinuria) were not associated with clinical events and were not considered to be related to the study vaccine. Vaccinations were generally well-tolerated. Strong IgG antibody responses and the absence of clinically significant laboratory abnormalities support further development of the bivalent rLP2086 vaccine (www.clinicaltrials.gov; identifier: NCT00879814).
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[Use of spirulina supplement for nutritional management of HIV-infected patients: study in Bangui, Central African Republic].
Yamani, E, Kaba-Mebri, J, Mouala, C, Gresenguet, G, Rey, JL
Medecine tropicale : revue du Corps de sante colonial. 2009;(1):66-70
Abstract
Treatment of HIV-infected persons including nutritional management is a major concern in Africa and in particular in the Central African Republic (CAR). This six-month randomized prospective longitudinal study was carried out at the Friends of Africa Center that was a facility for comprehensive management of persons infected and affected by HIV in Banqui, CAR. The purpose of the study was to assess the impact of spirulina supplement on clinical and laboratory findings in HIV-infected patients who were not indications for ARV treatment. A total of 160 patients were randomly assigned to two groups. Patients in group 1 (n=79) received 10 grams of spirulina per day on a regular basis while patients in group 2 (n = 81) received a placebo. In addition patients in both groups received dietary products supplied by the World Food Program (WFP). Follow-up of the 160 patients at three and six months showed that 16 patients had been lost from follow-up and 16 had died, with no difference in distribution between the two groups. A significant improvement in the main follow-up criteria, i.e., weight, arm girth, number of infectious episodes, CD4 count, and protidemia, was observed in both groups. No difference was found between the two groups except with regard to protidemia and creatinemia that were higher in the group receiving spirulina supplement. From a clinical standpoint results were less clear-cut since the Karnofsky score was better in the group receiving spirulina than in the group receiving the placebo at 3 months but not at 6 months and fewer patients presented pneumonia at six months. Further study over a longer period will be needed to determine if spirulina is useful and to evaluate if higher doses can have beneficial nutritional and immunitary effects without adverse effects, in particular renal problems.
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CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC-EURGAST study.
Palli, D, Masala, G, Del Giudice, G, Plebani, M, Basso, D, Berti, D, Numans, ME, Ceroti, M, Peeters, PH, Bueno de Mesquita, HB, et al
International journal of cancer. 2007;(4):859-67
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Abstract
Helicobacter pylori (H. pylori), atrophic gastritis, dietary and life-style factors have been associated with gastric cancer (GC). These factors have been evaluated in a large case-control study nested in the European Prospective Investigation into Cancer and Nutrition carried out in 9 countries, including the Mediterranean area. Participants, enrolled in 1992-1998, provided life-style and dietary information and a blood sample (360,000; mean follow-up: 6.1 years). For 233 GC cases diagnosed after enrolment and their 910 controls individually-matched by center, gender, age and blood donation date H. pylori antibodies (antilysate and antiCagA) and plasma Pepsinogen A (PGA) were measured by ELISA methods. Severe chronic atrophic gastritis (SCAG) was defined as PGA circulating levels <22 microg/l. Overall, in a conditional logistic regression analysis adjusted for education, smoke, weight and consumption of total vegetables, fruit, red and preserved meat, H. pylori seropositivity was associated with GC risk. Subjects showing only antibodies anti-H. pylori lysate, however, were not at increased risk, while those with antiCagA antibodies had a 3.4-fold increased risk. Overall, the odds ratio associated with SCAG was 3.3 (95% CI 2.2-5.2). According to site, the risk of noncardia GC associated with CagA seropositivity showed a further increase (OR 6.5; 95% CI 3.3-12.6); on the other hand, a ten-fold increased risk of cardia GC was associated with SCAG (OR 11.0; 95% CI 3.0-40.9). These results support the causal relationship between H. pylori CagA+ strains infection, and GC in these European populations even after taking into account dietary habits. This association was limited to distal GC, while serologically defined SCAG was strongly associated with cardia GC, thus suggesting a divergent risk pattern for these 2 sites.
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Nutrition rehabilitation of undernourished children utilizing Spiruline and Misola.
Simpore, J, Kabore, F, Zongo, F, Dansou, D, Bere, A, Pignatelli, S, Biondi, DM, Ruberto, G, Musumeci, S
Nutrition journal. 2006;:3
Abstract
BACKGROUND Malnutrition constitutes a public health problem throughout the world and particularly in developing countries. AIMS The objective of the study is to assess the impact of an elementary integrator composed of Spiruline (Spirulina platensis) and Misola (millet, soja, peanut) produced at the Centre Medical St Camille (CMSC) of Ouagadougou, Burkina Faso, on the nutritional status of undernourished children. MATERIALS AND METHODS 550 undernourished children of less than 5 years old were enrolled in this study, 455 showed severe marasma, 57 marasma of medium severity and 38 kwashiorkor plus marasma. We divided the children randomly into four groups: 170 were given Misola (731 +/- 7 kcal/day), 170 were given Spiruline plus traditional meals (748 +/- 6 kcal/day), 170 were given Spiruline plus Misola (767 +/- 5 kcal/day). Forty children received only traditional meals (722 +/- 8 kcal/day) and functioned as the control group. The duration of this study was eight weeks. RESULTS AND DISCUSSION Anthropometrics and haematological parameters allowed us to appreciate both the nutritional and biological evolution of these children. The rehabilitation with Spiruline plus Misola (this association gave an energy intake of 767 +/- 5 kcal/day with a protein assumption of 33.3 +/- 1.2 g a day), both greater than Misola or Spiruline alone, seems to correct weight loss more quickly. CONCLUSION Our results indicate that Misola, Spiruline plus traditional meals or Spiruline plus Misola are all a good food supplement for undernourished children, but the rehabilitation by Spiruline plus Misola seems synergically favour the nutrition rehabilitation better than the simple addition of protein and energy intake.
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Prospective analysis of the association of infection with CagA bearing strains of Helicobacter pylori and coronary heart disease.
Singh, RK, McMahon, AD, Patel, H, Packard, CJ, Rathbone, BJ, Samani, NJ
Heart (British Cardiac Society). 2002;(1):43-6
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Abstract
OBJECTIVE To see whether it was possible to replicate in a prospective study the association recently reported between infection with the more virulent (type 1) cytotoxin associated gene A (CagA) antigen carrying strains of Helicobacter pylori and increased risk of coronary heart disease. DESIGN AND SETTING Nested case-control study in a clinical outcomes trial. SUBJECTS Participants in the West of Scotland coronary prevention study. METHODS H pylori CagA serological status was determined in plasma samples of 201 subjects (cases) who subsequently had a coronary event during follow up and in 414 subjects (controls) matched for age and smoking who remained event-free, using a semiquantitative commercial enzyme linked immunosorbent assay (ELISA) kit against the p120 antigen of CagA. RESULTS 105 (52%) in the case group and 176 (43%) in the control group were seropositive (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.06 to 2.10, p = 0.022). The association remained significant after adjustment for blood pressure, body mass index, plasma concentrations of low density lipoprotein and high density lipoprotein cholesterol, history of hypertension and diabetes, statin treatment, and socioeconomic status (OR 1.51, 95% CI 1.06 to 2.16, p = 0.023). Baseline inflammatory markers (white cell count, C reactive protein, fibrinogen) were not significantly increased in either H pylori CagA positive cases or controls. CONCLUSIONS The findings provide support from a prospective study for the hypothesis that there is an association between infection with CagA bearing strains of H pylori and coronary heart disease. The mechanism(s) underlying the association remain to be elucidated.