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2.
Neurogastroenterol Motil ; 36(4): e14751, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38287443

ABSTRACT

BACKGROUND: A previous exploratory study demonstrated the ability of the Lab4 probiotic to alleviate the symptoms of IBS, and post hoc data analysis indicated greatest improvements in the female subgroup. The aim of this study is to confirm the impact of this multistrain probiotic on IBS symptom severity in females. METHODS: An 8-week, single-center, randomized, double-blinded, placebo-controlled, superiority study in 70 females with Rome IV-diagnosed irritable bowel syndrome (IBS) receiving the Lab4 probiotic (25 billion colony-forming units) daily or a matched placebo. Changes from baseline in the IBS-symptom severity score (IBS-SSS), daily bowel habits, anxiety, depression, IBS-related control, and avoidance behavior, executive function, and the fecal microbiota composition were assessed. The study was prospectively registered: ISRCTN 14866272 (registration date 20/07/22). KEY RESULTS: At the end of the study, there were significant between-group reductions in IBS-SSS (-85.0, p < 0.0001), anxiety and depression scores (-1.9, p = 0.0002 and -2.4, p < 0.0001, respectively), and the IBS-related control and avoidance behavior score (-7.5, p = 0.0002), all favoring the probiotic group. A higher proportion of the participants in the probiotic group had normal stool form (p = 0.0106) and/or fewer defecations with loose stool form (p = 0.0311). There was little impact on the overall diversity of the fecal microbiota but there were significant differences in Roseburia, Holdemanella, Blautia, Agathobacter, Ruminococcus, Prevotella, Bacteroides, and Anaerostipes between the probiotic and placebo groups at the end of the study. CONCLUSIONS & INFERENCES: Daily supplementation with this probiotic may represent an option to be considered in the management of IBS.


Subject(s)
Irritable Bowel Syndrome , Probiotics , Humans , Female , Treatment Outcome , Diarrhea , Anxiety/therapy , Probiotics/therapeutic use , Double-Blind Method
3.
Benef Microbes ; : 1-14, 2023 Apr 07.
Article in English | MEDLINE | ID: mdl-37026364

ABSTRACT

There is a growing awareness that supplementation with probiotic bacteria can impart beneficial effects during gastrointestinal disease, but less is known about the impact of probiotics on healthy subjects. Here, we report the outcomes of a post hoc analysis of recorded daily gastrointestinal events and bowel habits completed by healthy adults participating in a placebo-controlled, single-centre, randomised, double-blind, quadruple-arm probiotic tolerability study. Extensive screening ensured the healthy status of subjects entering the study and during a 2-week pre-intervention run-in period, a burden of gastrointestinal events (stomach pains, indigestion, acid reflux, stomach tightening, nausea and vomiting, stomach rumbling, bloating, belching and flatulence) was identified suggesting GI discomfort within the population. In the subsequent 12-week intervention period with 3 distinct probiotic formulations and a matched-placebo, reductions in the incidence rates of bloating, borborygmus, stomach pains, slow faecal transit and incomplete defecations were observed in the probiotic groups compared to the placebo. These results highlighted differing responses among the probiotic formulations tested and indicated potential anti-constipation effects. Product specific modulations in circulating interleukin-6 levels and in the composition of the gut microbiota were also detected. Together, these data suggest a role for probiotic supplementation to exert beneficial effects on the gastrointestinal functioning of healthy subjects and highlight the need for further longer-term studies in healthy populations to gain a greater understanding of the impact of probiotics.

4.
Benef Microbes ; 12(5): 431-440, 2021 Oct 11.
Article in English | MEDLINE | ID: mdl-34511049

ABSTRACT

In a double-blind, randomised, parallel-group, placebo-controlled study, healthy school children aged 3-10 years received a probiotic based supplement daily for 6 months to assess the impact on the incidence and duration of upper respiratory tract infection (URTI) symptoms. The intervention comprised Lab4 probiotic (Lactobacillus acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20 and Bifidobacterium animalis subsp. lactis CUL34) at 12.5 billion cfu/day plus 50 mg vitamin C or a matching placebo. 171 children were included in the analysis (85 in placebo and 86 in active group). Incidence of coughing was 16% (P=0.0300) significantly lower in the children receiving the active intervention compared to the placebo. No significant differences in the incidence rate of other URTI symptoms were observed. There was significantly lower risk of experiencing five different URTI related symptoms in one day favouring the active group (Risk ratio: 0.31, 95% confidence interval: 0.12, 0.81, P=0.0163). Absenteeism from school and the use of antibiotics was also significantly reduced for those in the active group (-16%, P=0.0060 and -27%, P=0.0203, respectively). Our findings indicate that six months daily supplementation with the Lab4 probiotic and vitamin C combination reduces the incidence of coughing, absenteeism and antibiotic usage in 3 to 10 year old children.


Subject(s)
Ascorbic Acid/administration & dosage , Probiotics , Respiratory Tract Infections , Anti-Bacterial Agents , Bifidobacterium , Child , Child, Preschool , Double-Blind Method , Humans , Lactobacillus acidophilus , Probiotics/therapeutic use , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/prevention & control , Vitamins/administration & dosage
5.
Genomics ; 113(6): 4028-4038, 2021 11.
Article in English | MEDLINE | ID: mdl-34391865

ABSTRACT

Draft genome sequences of the Lab4 probiotic consortium were deposited in Genbank: Bifidobacterium animalis subsp lactis CUL34 (PRJNA482550), Bifidobacterium bifidum CUL20 (PRJNA559984), Lactobacillus acidophilus CUL60 (PRJNA482335), Lactobacillus acidophilus CUL21 (PRJNA482434). Probiogenomic analyses confirmed existing taxonomies and identified putative gene sequences that were functionally related to the performance of each organism during in vitro assessments of bile and acid tolerability, adherence to enterocytes and susceptibility to antibiotics. Genomic stability predictions identified no significant risk of gene acquisition of both antibiotic resistance and virulence genes. These observations were supported by acute phase and repeat dose tolerability studies in Wistar rats. High doses of Lab4 did not result in mortalities, clinical/histopathological abnormalities nor systemic toxicity. Increased faecal numbers of Lab4 in supplemented rats implied survival through the gastrointestinal tract and/or impact the intestinal microbiota composition. In summary, this study provides multifaceted support for probiotic functionality and the safety of the Lab4 consortium.


Subject(s)
Bifidobacterium , Probiotics , Animals , Bifidobacterium/genetics , Feces/microbiology , Lactobacillus acidophilus/genetics , Rats , Rats, Wistar
6.
Sci Rep ; 11(1): 5, 2021 01 06.
Article in English | MEDLINE | ID: mdl-33408364

ABSTRACT

This 9-month randomised, parallel, double-blind, single-centre, placebo-controlled study (PROBE, ISRCTN18030882) assessed the impact of probiotic supplementation on bodyweight. Seventy overweight Bulgarian participants aged 45-65 years with BMI 25-29.9 kg/m2 received a daily dose of the Lab4P probiotic comprising lactobacilli and bifidobacteria (50 billion cfu/day). Participants maintained their normal diet and lifestyle over the duration of the study. The primary outcome was change from baseline in body weight and secondary outcomes included changes in waist circumference, hip circumference and blood pressure. A significant between group decrease in body weight (3.16 kg, 95% CI 3.94, 2.38, p < 0.0001) was detected favouring the probiotic group. Supplementation also resulted in significant between group decreases in waist circumference (2.58 cm, 95% CI 3.23, 1.94, p < 0.0001) and hip circumference (2.66 cm, 95% CI 3.28, 2.05, p < 0.0001) but no changes in blood pressure were observed. These findings support the outcomes of a previous shorter-term Lab4P intervention study in overweight and obese participants (PROMAGEN, ISRCTN12562026). We conclude that Lab4P has consistent weight modulation capability in free-living overweight adults.


Subject(s)
Dietary Supplements , Overweight/diet therapy , Probiotics/therapeutic use , Weight Loss/drug effects , Bifidobacterium , Blood Pressure/drug effects , Body Size/drug effects , Body Weight/drug effects , Bulgaria , Double-Blind Method , Female , Humans , Lactobacillus , Male , Middle Aged , Waist Circumference/drug effects
7.
Physiol Plant ; 172(2): 748-761, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33247448

ABSTRACT

Water deficit is the most limiting abiotic stress to plants because it affects several physiological and biochemical processes. Brassinosteroids, including 24-epibrassinolide (EBR), are steroids that regulate growth and positively act on gas exchange. This research aims to determine whether EBR can attenuate the negative effects of water deficit, revealing possible contributions of this steroid on photosynthetic machinery of young Eucalyptus urophylla plants under water deficit. The experiment had a completely randomized factorial design with two water conditions (control and water deficit) and three levels of EBR (0, 50, and 100 nM EBR). Water deficit caused a decrease in the levels of total chlorophyll and carotenoids, but these photosynthetic pigments increased by 135 and 226%, respectively, in plants sprayed with EBR when compared to the water deficit + 0 nM EBR treatment. Regarding the antioxidant system, 100 nM EBR induced significant increments in superoxide dismutase (42%), catalase (52%), ascorbate peroxidase (147%), and peroxidase (204%). Steroid application in E. urophylla plants exposed to water deficit increased the effective quantum yield of the photosystem II (PSII) photochemistry and electron transport rate. However, interestingly, it decreased the nonphotochemical quenching and relative energy excess at the PSII level, indicating improvements related to PSII efficiency. This research revealed that application of 100 nM EBR attenuated the negative effects caused by water deficit, being explained by the positive repercussions on antioxidant enzyme activities, chloroplastic pigments, PSII efficiency, electron flux, and net photosynthetic rate.


Subject(s)
Brassinosteroids , Eucalyptus , Brassinosteroids/metabolism , Brassinosteroids/pharmacology , Chlorophyll , Droughts , Eucalyptus/metabolism , Homeostasis , Oxidation-Reduction , Photosynthesis
8.
Sci Rep ; 10(1): 4183, 2020 03 06.
Article in English | MEDLINE | ID: mdl-32144319

ABSTRACT

In an exploratory, block-randomised, parallel, double-blind, single-centre, placebo-controlled superiority study (ISRCTN12562026, funded by Cultech Ltd), 220 Bulgarian participants (30 to 65 years old) with BMI 25-34.9 kg/m2 received Lab4P probiotic (50 billion/day) or a matched placebo for 6 months. Participants maintained their normal diet and lifestyle. Primary outcomes were changes in body weight, BMI, waist circumference (WC), waist-to-height ratio (WtHR), blood pressure and plasma lipids. Secondary outcomes were changes in plasma C-reactive protein (CRP), the diversity of the faecal microbiota, quality of life (QoL) assessments and the incidence of upper respiratory tract infection (URTI). Significant between group decreases in body weight (1.3 kg, p < 0.0001), BMI (0.045 kg/m2, p < 0.0001), WC (0.94 cm, p < 0.0001) and WtHR (0.006, p < 0.0001) were in favour of the probiotic. Stratification identified greater body weight reductions in overweight subjects (1.88%, p < 0.0001) and in females (1.62%, p = 0.0005). Greatest weight losses were among probiotic hypercholesterolaemic participants (-2.5%, p < 0.0001) alongside a significant between group reduction in small dense LDL-cholesterol (0.2 mmol/L, p = 0.0241). Improvements in QoL and the incidence rate ratio of URTI (0.60, p < 0.0001) were recorded for the probiotic group. No adverse events were recorded. Six months supplementation with Lab4P probiotic resulted in significant weight reduction and improved small dense low-density lipoprotein-cholesterol (sdLDL-C) profiles, QoL and URTI incidence outcomes in overweight/obese individuals.


Subject(s)
Bifidobacterium/physiology , Lactobacillus/physiology , Obesity/drug therapy , Obesity/microbiology , Overweight/drug therapy , Overweight/microbiology , Probiotics/therapeutic use , Body Weight/physiology , Double-Blind Method , Female , Humans , Male , Quality of Life , Randomized Controlled Trials as Topic , Respiratory Tract Infections , Waist Circumference/physiology , Weight Loss/physiology
9.
Benef Microbes ; 10(4): 437-447, 2019 Apr 19.
Article in English | MEDLINE | ID: mdl-30827148

ABSTRACT

Neurodegeneration has been linked to changes in the gut microbiota and this study compares the neuroprotective capability of two bacterial consortia, known as Lab4 and Lab4b, using the established SH-SY5Y neuronal cell model. Firstly, varying total antioxidant capacities (TAC) were identified in the intact cells from each consortia and their secreted metabolites, referred to as conditioned media (CM). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Crystal Violet (CV) assays of cell viability revealed that Lab4 CM and Lab4b CM could induce similar levels of proliferation in SH-SY5Y cells and, despite divergent TAC, possessed a comparable ability to protect undifferentiated and retinoic acid-differentiated cells from the cytotoxic actions of rotenone and undifferentiated cells from the cytotoxic actions of 1-methyl-4-phenylpyridinium iodide (MPP+). Lab4 CM and Lab4b CM also had the ability to attenuate rotenone-induced apoptosis and necrosis with Lab4b inducing the greater effect. Both consortia showed an analogous ability to attenuate intracellular reactive oxygen species accumulation in SH-SY5Y cells although the differential upregulation of genes encoding glutathione reductase and superoxide dismutase by Lab4 CM and Lab4b CM, respectively, implicates the involvement of consortia-specific antioxidative mechanisms of action. This study implicates Lab4 and Lab4b as potential neuroprotective agents and justifies their inclusion in further in vivo studies.


Subject(s)
Microbial Consortia/physiology , Neuroprotective Agents/pharmacology , Probiotics/pharmacology , 1-Methyl-4-phenylpyridinium/toxicity , Antioxidants/analysis , Antioxidants/metabolism , Apoptosis/drug effects , Bifidobacterium/classification , Bifidobacterium/metabolism , Cell Line, Tumor , Cell Survival , Culture Media, Conditioned/chemistry , Culture Media, Conditioned/pharmacology , Humans , Lactobacillus/classification , Lactobacillus/metabolism , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Neuroprotective Agents/chemistry , Oxidative Stress/drug effects , Probiotics/chemistry , Reactive Oxygen Species/metabolism , Rotenone/toxicity
10.
R Soc Open Sci ; 5(10): 180136, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30473801

ABSTRACT

Invasive mammalian predators are linked to terrestrial vertebrate extinctions worldwide. Prey naïveté may explain the large impact invasive predators have on native prey; prey may fail to detect and react appropriately to the cues of novel predators, which results in high levels of depredation. In Australia, the feral cat (Felis catus) and the red fox (Vulpes vulpes) are implicated in more than 30 animal extinctions and the naïveté of native prey is often used to explain this high extinction rate. Reptiles are one group of animals that are heavily preyed upon by F. catus and V. vulpes. However, very few studies have examined whether reptiles are naive to their cues. In this study, we examine the ability of two native reptile species (Morethia boulengeri and Christinus marmoratus) to detect and distinguish between the chemical cues of two invasive predators (V. vulpes and F. catus) and three native predators (spotted-tailed quoll, Dasyurus maculatus; dingo, Canis lupus dingo; eastern brown snake, Pseudonaja textilis), as well as two non-predator controls (eastern grey kangaroo, Macropus giganteus and water). We conducted experiments to quantify the effects of predator scents on lizard foraging (the amount of food eaten) during 1 h trials within Y-maze arenas. We found both study species reduced the amount they consumed when exposed to predator scents-both native and invasive-indicating that these species are not naive to invasive predators. An evolved generalized predator-recognition system, rapid evolution or learned behaviour could each explain the lack of naïveté in some native Australian reptiles towards invasive predators.

11.
Sci Rep ; 7(1): 2883, 2017 06 06.
Article in English | MEDLINE | ID: mdl-28588193

ABSTRACT

Hypercholesterolaemia is a major risk factor for cardiovascular disease and it has been found that some probiotic bacteria possess cholesterol-lowering capabilities. In this study, the ability of the Lab4 probiotic consortium to hydrolyse bile salts, assimilate cholesterol and regulate cholesterol transport by polarised Caco-2 enterocytes was demonstrated. Furthermore, in wild-type C57BL/6J mice fed a high fat diet, 2-weeks supplementation with Lab4 probiotic consortium plus Lactobacillus plantarum CUL66 resulted in significant reductions in plasma total cholesterol levels and suppression of diet-induced weight gain. No changes in plasma levels of very low-density lipoprotein/low-density lipoprotein, high-density lipoprotein, triglycerides, cytokines or bile acids were observed. Increased amounts of total and unconjugated bile acids in the faeces of the probiotic-fed mice, together with modulation of hepatic small heterodimer partner and cholesterol-7α-hydroxylase mRNA expression, implicates bile salt hydrolase activity as a potential mechanism of action. In summary, this study demonstrates the cholesterol-lowering efficacy of short-term feeding of the Lab4 probiotic consortium plus L. plantarum CUL66 in wild-type mice and supports further assessment in human trials.


Subject(s)
Anticholesteremic Agents/pharmacology , Microbial Consortia/drug effects , Probiotics , Animals , Bile Acids and Salts/blood , Bile Acids and Salts/metabolism , Body Weight , Caco-2 Cells , Cholesterol/metabolism , Colon/metabolism , Colon/microbiology , Cytokines/blood , Diet, High-Fat , Humans , Lactobacillus plantarum , Lipids/blood , Liver/metabolism , Mice , Mice, Inbred C57BL
12.
Benef Microbes ; 7(3): 443-51, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26839071

ABSTRACT

Hypercholesterolemia drives the development of cardiovascular disease, the leading cause of mortality in western society. Supplementation with probiotics that interfere with cholesterol metabolism may provide a contribution to disease prevention. Lactobacillus plantarum CUL66 (NCIMB 30280) has been assessed in vitro for its ability to impact cholesterol absorption. L. plantarum CUL66 tested positive for bile salt hydrolase activity and the ability to assimilate cholesterol from culture media. RT-qPCR analysis showed that the bacterium significantly decreased the expression of Niemann-Pick C1-like 1 and ATP-binding cassette transporter-1 in polarised Caco-2 cells after 6 h exposure. Conversely, the expression of ATP-binding cassette sub-family G member (ABCG)-5 and ABCG-8, and 3-hydroxy-3-methylglutaryl-CoA reductase were significantly increased. Using a radiolabelled assay, we also observed significant reductions in the uptake and basolateral efflux of cholesterol by Caco-2 cells exposed to L. plantarum CUL66. This in vitro study identified L. plantarum CUL66 as a cholesterol lowering bacteria by highlighting its ability to beneficially regulate multiple in vitro events associated with intestinal cholesterol metabolism and provides evidence of efficacy for its inclusion in future in vivo studies.


Subject(s)
Cholesterol/metabolism , Enterocytes/metabolism , Enterocytes/microbiology , Homeostasis , Lactobacillus plantarum/growth & development , Lactobacillus plantarum/metabolism , Caco-2 Cells , Gene Expression Profiling , Humans
13.
J Appl Clin Med Phys ; 16(1): 5238, 2015 Jan 08.
Article in English | MEDLINE | ID: mdl-25679179

ABSTRACT

For accurate delivery of volumetric-modulated arc therapy (VMAT), the gantry position should be synchronized with the multileaf collimator (MLC) leaf positions and the dose rate. This study, therefore, aims to implement quality control (QC) of VMAT synchronization, with as few arcs as possible and with minimal data handling time, using portal imaging. A steel bar of diameter 12 mm is accurately positioned in the G-T direction, 80 mm laterally from the isocenter. An arc prescription irradiates the bar with a 16 mm × 220 mm field during a complete 360° arc, so as to cast a shadow of the bar onto the portal imager. This results in a sinusoidal sweep of the field and shadow across the portal imager and back. The method is evaluated by simulating gantry position errors of 1°-9° at one control point, dose errors of 2 monitor units to 20 monitor units (MU) at one control point (0.3%-3% overall), and MLC leaf position errors of 1 mm - 6 mm at one control point. Inhomogeneity metrics are defined to characterize the synchronization of all leaves and of individual leaves with respect to the complete set. Typical behavior is also investigated for three models of accelerator. In the absence of simulated errors, the integrated images show uniformity, and with simulated delivery errors, irregular patterns appear. The inhomogeneity metrics increase by 67% due to a 4° gantry position error, 33% due to an 8 MU (1.25%) dose error, and 70% due to a 2 mm MLC leaf position error. The method is more sensitive to errors at gantry angle 90°/270° than at 0°/180° due to the geometry of the test. This method provides fast and effective VMAT QC suitable for inclusion in a monthly accelerator QC program. The test is able to detect errors in the delivery of individual control points, with the possibility of using movie images to further investigate suspicious image features.


Subject(s)
Diagnostic Imaging , Neoplasms/radiotherapy , Particle Accelerators/standards , Quality Assurance, Health Care/methods , Quality Control , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Humans , Radiotherapy Dosage
14.
Eur J Clin Nutr ; 69(3): 373-9, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25205320

ABSTRACT

BACKGROUND: This pilot study investigates the efficacy of a probiotic consortium (Lab4) in combination with vitamin C on the prevention of respiratory tract infections in children attending preschool facilities. SUBJECTS/METHODS: In a double-blind, randomised, placebo-controlled pilot study with children aged 3-6 years, 57 received 1.25 × 10(10) colony-forming units of Lactobacillus acidophilus CUL21 (NCIMB 30156), Lactobacillus acidophilus CUL60 (NCIMB 30157), Bifidobacterium bifidum CUL20 (NCIMB 30153) and Bifidobacterium animalis subsp. lactis CUL34 (NCIMB 30172) plus 50 mg vitamin C or a placebo daily for 6 months. RESULTS: Significant reductions in the incidence rate of upper respiratory tract infection (URTI; 33%, P=0.002), the number of days with URTI symptoms (mean difference: -21.0, 95% confidence interval (CI):-35.9, -6.0, P=0.006) and the incidence rate of absence from preschool (30%, P=0.007) were observed in the active group compared with the placebo. The number of days of use of antibiotics, painkillers, cough medicine or nasal sprays was lower in the active group and reached significance for use of cough medicine (mean difference: -6.6, 95% CI: -12.9, -0.3, P=0.040). No significant differences were observed in the incidence rate ratio or duration of lower respiratory tract infection or in the levels of plasma cytokines, salivary immunoglobulin A or urinary metabolites. CONCLUSIONS: Supplementation with a probiotic/vitamin C combination may be beneficial in the prevention and management of URTIs.


Subject(s)
Ascorbic Acid/therapeutic use , Bifidobacterium , Lactobacillus acidophilus , Probiotics/therapeutic use , Respiratory Tract Infections/prevention & control , Vitamins/therapeutic use , Absenteeism , Antitussive Agents/therapeutic use , Child, Preschool , Cough/drug therapy , Cough/etiology , Double-Blind Method , Female , Humans , Incidence , Male , Pilot Projects , Respiratory Tract Infections/complications , Schools
15.
Benef Microbes ; 4(4): 313-7, 2013 Dec 01.
Article in English | MEDLINE | ID: mdl-24311314

ABSTRACT

The objective of this study was to examine the effect of daily probiotic supplementation upon the immune profile of healthy participants by the assessment of ex vivo cytokine production. Twenty healthy adult volunteers received a multi-strain probiotic supplement consisting of two strains of Lactobacillus acidophilus (CUL60 and CUL21), Bifidobacterium lactis (CUL34) and Bifidobacterium bifidum (CUL20) and fructooligosaccharide for 12 weeks. Blood samples were collected at baseline, 6 and 12 weeks. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured ex vivo in the presence or absence of lipopolysaccharide and cytokine production was assessed. Postintervention, a significant decrease in the production of interleukin-6 and interleukin-1ß was apparent when PBMCs were incubated in the presence of lipopolysaccharide, whilst a significant increase in IL-10 and transforning growth factor-ß production was seen when the cells were incubated without an additional stimulus. This preliminary study demonstrates the potential of a multi-strain probiotic supplement to alter the immune response as demonstrated by changes in ex vivo cytokine production. Such results demonstrate the potential benefit of probiotic supplementation for healthy individuals and warrants further investigation.


Subject(s)
Bifidobacterium/physiology , Cytokines/metabolism , Diet/methods , Lactobacillus acidophilus/physiology , Leukocytes, Mononuclear/immunology , Oligosaccharides/administration & dosage , Probiotics/administration & dosage , Bifidobacterium/immunology , Healthy Volunteers , Humans , Lactobacillus acidophilus/immunology
16.
J Appl Clin Med Phys ; 14(2): 4136, 2013 May 06.
Article in English | MEDLINE | ID: mdl-23470941

ABSTRACT

The Agility multileaf collimator (Elekta AB, Stockholm, Sweden) has 160 leaves of projected width 0.5 cm at the isocenter, with maximum leaf speed 3.5 cms-1. These characteristics promise to facilitate fast and accurate delivery of radiotherapy, particularly volumetric-modulated arc therapy (VMAT). The aim of this study is therefore to create a beam model for the Pinnacle3 treatment planning system (Philips Radiation Oncology Systems, Fitchburg, WI), and to use this beam model to explore the performance of the Agility MLC in delivery of VMAT. A 6 MV beam model was created and verified by measuring doses under irregularly shaped fields. VMAT treatment plans for five typical head-and-neck patients were created using the beam model and delivered using both binned and continuously variable dose rate (CVDR). Results were compared with those for an MLCi unit without CVDR. The beam model has similar parameters to those of an MLCi model, with interleaf leakage of only 0.2%. The verification of irregular fields shows a mean agreement between measured and planned dose of 1.3% (planned dose higher). The Agility VMAT head-and-neck plans show equivalent plan quality and delivery accuracy to those for an MLCi unit, with 95% of verification measurements within 3% and 3 mm of planned dose. Mean delivery time is 133 s with the Agility head and CVDR, 171 s without CVDR, and 282 s with an MLCi unit. Pinnacle3 has therefore been shown to model the Agility MLC accurately, and to provide accurate VMAT treatment plans which can be delivered significantly faster with Agility than with an MLCi.


Subject(s)
Head and Neck Neoplasms/radiotherapy , Radiometry/instrumentation , Radiometry/methods , Radiotherapy Planning, Computer-Assisted/instrumentation , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/instrumentation , Radiotherapy, Intensity-Modulated/methods , Equipment Design , Equipment Failure Analysis , Humans , Radiotherapy Dosage , Reproducibility of Results , Sensitivity and Specificity
17.
Nucleic Acids Res ; 41(Database issue): D834-40, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23143269

ABSTRACT

We created SynSysNet, available online at http://bioinformatics.charite.de/synsysnet, to provide a platform that creates a comprehensive 4D network of synaptic interactions. Neuronal synapses are fundamental structures linking nerve cells in the brain and they are responsible for neuronal communication and information processing. These processes are dynamically regulated by a network of proteins. New developments in interaction proteomics and yeast two-hybrid methods allow unbiased detection of interactors. The consolidation of data from different resources and methods is important to understand the relation to human behaviour and disease and to identify new therapeutic approaches. To this end, we established SynSysNet from a set of ∼1000 synapse specific proteins, their structures and small-molecule interactions. For two-thirds of these, 3D structures are provided (from Protein Data Bank and homology modelling). Drug-target interactions for 750 approved drugs and 50 000 compounds, as well as 5000 experimentally validated protein-protein interactions, are included. The resulting interaction network and user-selected parts can be viewed interactively and exported in XGMML. Approximately 200 involved pathways can be explored regarding drug-target interactions. Homology-modelled structures are downloadable in Protein Data Bank format, and drugs are available as MOL-files. Protein-protein interactions and drug-target interactions can be viewed as networks; corresponding PubMed IDs or sources are given.


Subject(s)
Databases, Protein , Nerve Tissue Proteins/drug effects , Nerve Tissue Proteins/metabolism , Protein Interaction Mapping , Synapses/drug effects , Synapses/metabolism , Humans , Internet , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/genetics , Protein Conformation , User-Computer Interface
18.
Phys Med Biol ; 50(15): N187-94, 2005 Aug 07.
Article in English | MEDLINE | ID: mdl-16030376

ABSTRACT

Routine quality control (QC) and optimization of image quality of reconstructed images in single photon emission computed tomography (SPECT) and positron emission tomography (PET) remains a relatively qualitative exercise. With the advent of combined SPECT/CT and PET/CT devices, and accurate post hoc co-registration algorithms, the potential exists to utilize high resolution structural information for QC evaluation in addition to their use for anatomical correlation in clinical studies. The aim of this work was to explore, in principle, the uses of x-ray CT data of QC phantoms used in SPECT and PET to develop more objective assessments of performance of the emission tomographic (ET) devices and reconstructed data. A CT reconstruction of a novel ET QC phantom was segmented into the various compartments it contained. Using software, the voxel values in the different compartments were then altered to correspond to the concentration of the radioactivity in the actual scan of the same phantom on the SPECT system. This produces a high resolution version of a 'perfect' ET scan. Image co-registration techniques were then used to spatially align the synthetic high resolution SPECT scan to the measured SPECT scan. Various parameters can then be objectively derived from the registered data, for example, image contrast, spatial resolution, spatial non-uniformity, etc. In this study, we have used this approach to estimate spatial resolution (full width at half maximum, FWHM) and recovered contrast in reconstructed images of a SPECT phantom. Two independent methods were used to measure spatial resolution, obtaining excellent agreement. In conclusion, the ability to produce high resolution synthetic phantoms in emission tomography QC affords an objective approach to assessing system performance and optimizing protocols which is readily automated and quantifiable.


Subject(s)
Algorithms , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Quality Assurance, Health Care/methods , Subtraction Technique , Tomography, Emission-Computed, Single-Photon/methods , Information Storage and Retrieval/methods , Phantoms, Imaging , Quality Control , Reproducibility of Results , Sensitivity and Specificity , Tomography, Emission-Computed, Single-Photon/instrumentation , Tomography, X-Ray Computed/instrumentation , Tomography, X-Ray Computed/methods
19.
Chem Commun (Camb) ; (14): 1895-7, 2005 Apr 14.
Article in English | MEDLINE | ID: mdl-15795779

ABSTRACT

We herein report and discuss electron transport within a Au/H2S nanoscale device and thereby highlight a phenomenon that may be used in the development of a novel on-chip H2S sensor.

20.
Genome Res ; 15(1): 174-83, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15590942

ABSTRACT

We present an analysis of the chicken (Gallus gallus) transcriptome based on the full insert sequences for 19,626 cDNAs, combined with 485,337 EST sequences. The cDNA data set has been functionally annotated and describes a minimum of 11,929 chicken coding genes, including the sequence for 2260 full-length cDNAs together with a collection of noncoding (nc) cDNAs that have been stringently filtered to remove untranslated regions of coding mRNAs. The combined collection of cDNAs and ESTs describe 62,546 clustered transcripts and provide transcriptional evidence for a total of 18,989 chicken genes, including 88% of the annotated Ensembl gene set. Analysis of the ncRNAs reveals a set that is highly conserved in chickens and mammals, including sequences for 14 pri-miRNAs encoding 23 different miRNAs. The data sets described here provide a transcriptome toolkit linked to physical clones for bioinformaticians and experimental biologists who wish to use chicken systems as a low-cost, accessible alternative to mammals for the analysis of vertebrate development, immunology, and cell biology.


Subject(s)
Chickens/genetics , DNA, Complementary/genetics , Expressed Sequence Tags , Gene Library , Transcription, Genetic/genetics , Animals , Cloning, Molecular/methods , Computational Biology/methods , DNA, Complementary/physiology , Humans , MicroRNAs/genetics , RNA, Untranslated/genetics , Sequence Alignment/methods , Sequence Analysis, DNA/methods
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