Development of surfactant-coated alginate capsules containing Lactobacillus plantarum

A novel concept is proposed in which alginate capsules containing a model probiotic Lactobacillus plantarum strain are coated with different surfactants with the aim to enhance cell survival during passage initially through simulated gastric (SGF) and then intestinal (SIF) fluid. The surfactants investigated included the anionic sodium dodecyl sulphate (SDS) and ammonium lauryl sulphate (ALS), the cationic dimethyldioctadecylammonium chloride (DDAC), benzalkonium chloride (BZK) and hexadecyltrimethylammonium bromide (CTAB), and the zwitterionic lecithin. Coating the alginate capsules with CTAB, BZK, ALS and SDS resulted in worst survival (~ 4-9 log CFU/g decrease) compared to uncoated capsules (~3 log CFU/g decrease), after 1 hour exposure to SGF and two hours in SIF, which was most likely associated with their gradual penetration inside the microcapsules, as shown by confocal microscopy, and their antimicrobial effects. Coating the alginate capsules with DDAC improved cell survival compared to uncoated capsules (~1.2 CFU/g decrease), whereas coating with lecithin improved cell survival considerably, resulting in almost complete recovery of viable cells in SGF and SIF (~ 0.3 log CFU/g decrease). Although the interaction between alginate and lecithin was relatively weak as demonstrated by turbidity and contact angle measurements, it is likely that the protection was associated with the fact that lecithin was able to penetrate into the capsule rapidly, an observation that was supported by the fact that lecithin enhanced the viability of free cells in SGF and SIF. Lecithin has significant potential of being used as a coating material for probiotic containing capsules

Response to pulmonary arterial hypertension drug therapies in patients with pulmonary arterial hypertension and cardiovascular risk factors.

The age at diagnosis of pulmonary arterial hypertension (PAH) and the prevalence of cardiovascular (CV) risk factors are increasing. We sought to determine whether the response to drug therapy was influenced by CV risk factors in PAH patients. We studied consecutive incident PAH patients (n = 146) between January 1, 2008, and July 15, 2011. Patients were divided into two groups: the PAH-No CV group included patients with no CV risk factors (obesity, systemic hypertension, type 2 diabetes mellitus, permanent atrial fibrillation, mitral and/or aortic valve disease, and coronary artery disease), and the PAH-CV group included patients with at least one. The response to PAH treatment was analyzed in all the patients who received PAH drug therapy. The PAH-No CV group included 43 patients, and the PAH-CV group included 69 patients. Patients in the PAH-No CV group were younger than those in the PAH-CV group (P < 0.0001). In the PAH-No CV group, 16 patients (37%) improved on treatment and 27 (63%) did not improve, compared with 11 (16%) and 58 (84%) in the PAH-CV group, respectively (P = 0.027 after adjustment for age). There was no difference in survival at 30 months (P = 0.218). In conclusion, in addition to older age, CV risk factors may predict a reduced response to PAH drug therapy in patients with PAH

In vitro fermentability of xylo-oligosaccharide and xylo-polysaccharide fractions with different molecular weights by human faecal bacteria

Xylo-oligosaccharides and xylo-polysaccharides (XOS, XPS) produced by autohydrolysis of the fibre from oil palm empty fruit bunches (OPEFB) were purified using gel filtration chromatography to separate the XOS and XPS from the crude autohydrolysis liquor. Six mixed fractions of refined XOS and XPS with average degree of polymerisation (avDP) of 4-64 were obtained. These were characterised in terms of their composition and size by HPLC, MALDI-ToF-MS (selected fractions) and carbohydrate gel electrophoresis (PACE). They were assessed in batch culture fermentations using faecal inocula to determine their ability to modulate the human faecal microbiota in vitro by measuring the bacterial growth, organic acid production and the XOS assimilation profile. The gut microbiota was able to utilise all the substrates and there was a link between the XOS/XPS degree of polymerisation with the fermentation properties. In general, XOS/XPS preparations of lower avDP promote better Bifidobacterium growth and organic acid production

Development of chitosan-coated agar-gelatin particles for probiotic delivery and targeted release in the gastrointestinal tract

This study reports the development of a novel and simple formulation for probiotic delivery using chitosan-coated agar-gelatin gel particles. This methodology involves the production of agar-gelatin particles by thermally treating a mixture of agar and gelatin solutions at high temperatures (121°C) and subsequently coating with chitosan. The particles were able to protect the probiotic strain Lactobacillus plantarum NCIMB 8826 during incubation for 2 hours in simulated gastric fluid (pH 2) as no statistically significant loss (P > 0.05) in cell concentration was observed, and also resist dissolution in simulated intestinal fluid (pH 7.2). Interestingly, this protection is related to the fact that the intense thermal treatment affected the physicochemical properties of agars, and resulted in the formation of a strong and tight polymer network, as indicated by the X-ray diffraction (XRD) analysis. Using an in vitro faecal batch fermentation model simulating the conditions of the distal part of the large intestine (pH 6.7-6.9), it was demonstrated by quantitative real time PCR that the majority of L. plantarum cells were released from the agar-gelatin particles within 30 to 48 hours. Overall, this work led to the development of a novel methodology for the production of probiotic containing particles which is simpler compared to current encapsulation technologies, and has a lot of potential to be used for the controlled release of probiotics and potentially other solid bioactives in the large intestine

Longest common substring made fully dynamic

Given two strings S and T, each of length at most n, the longest common substring (LCS) problem is to find a longest substring common to S and T. This is a classical problem in computer science with an O(n)-time solution. In the fully dynamic setting, edit operations are allowed in either of the two strings, and the problem is to find an LCS after each edit. We present the first solution to this problem requiring sublinear time in n per edit operation. In particular, we show how to find an LCS after each edit operation in Õ(n2/3) time, after Õ(n)-time and space preprocessing. 1 This line of research has been recently initiated in a somewhat restricted dynamic variant by Amir et al. [SPIRE 2017]. More specifically, they presented an Õ(n)-sized data structure that returns an LCS of the two strings after a single edit operation (that is reverted afterwards) in Õ(1) time. At CPM 2018, three papers (Abedin et al., Funakoshi et al., and Urabe et al.) studied analogously restricted dynamic variants of problems on strings. We show that the techniques we develop can be applied to obtain fully dynamic algorithms for all of these variants. The only previously known sublinear-time dynamic algorithms for problems on strings were for maintaining a dynamic collection of strings for comparison queries and for pattern matching, with the most recent advances made by Gawrychowski et al. [SODA 2018] and by Clifford et al. [STACS 2018]. As an intermediate problem we consider computing the solution for a string with a given set of k edits, which leads us, in particular, to answering internal queries on a string. The input to such a query is specified by a substring (or substrings) of a given string. Data structures for answering internal string queries that were proposed by Kociumaka et al. [SODA 2015] and by Gagie et al. [CCCG 2013] are used, along with new ones, based on ingredients such as the suffix tree, heavy-path decomposition, orthogonal range queries, difference covers, and string periodicity

Probiotic microcarrier: a continuous folate producer

The recommended daily intake of folate (B-complex vitamin) for an adult varies between 200-400 µg, being the intake of folate inefficient due its extremely unstable chemical forms. The aim of this work is the creation of model to folate in situ production using probiotics. However, three main issues need to be overcome: (a) probiotic bacteria should be protected towards the gastric medium (encapsulation); (b) microcarriers size should be smaller than 100 µm, to avoid modifying food texture; and (c) microcarriers should adhere to gut epithelium in order to increase bacteria residence time. Lactococcus lactis cremoris was grown in milk (30ºC). Alginate-based microcarriers were produced and three layers were built using the layer-by-layer technique in that worder: poly-L-lysine; sodium alginate; chitosan. Confocal microscopy was used to confirm the consequent adhesion of the layers (poly-L-lysine/FITC; chitosan/rhodamine). After production the microcarriers where put into a 10 mL solution of KCl-HCl (pH 2 - 1 hour), at 100 rpm and then into a PBS solution (pH 7.2 - 3 hours) in order to mimic the passage through the gastrointestinal tract. The utilization of free bacteria (LLC) in milk showed an increase of folate content in 4.73 µg/L after 6 h. The average size of the microcarriers from 21.01 ± 0.49 µm to 39.84 ± 0.79 µm when the pH increased from 2 to 7.2. The size averages obtained were smaller than 100 µm and showed a swelling capacity (particles duplicate their size upon passing from pH 2 to pH 7.2), being confirmed by confocal microscopy images the correct adhesion of the different layers after this experiment and the stability of the microcarriers. Microcarriers produced through LbL showed great potential for encapsulation of probiotics, allowing their protection against harsh gastrointestinal conditions, predicting their use as a microcarrier for in situ folate production

Clinical predictors of all‐cause mortality in patients presenting to specialist heart failure clinic with raised NT‐proBNP and no heart failure

Aims Clinical outcomes for patients suspected of having heart failure (HF) who do not meet the diagnostic criteria of any type of HF by echocardiography remain unknown. The aim of this study was to investigate the clinical predictors of all‐cause mortality in patients with suspected HF, a raised N‐terminal pro‐b‐type natriuretic peptide (NTproBNP) and who do not meet the diagnostic criteria of any type of HF by echocardiography. Methods and results Relevant data were taken from the S heffield HEA rt F ailure (SHEAF) registry (222349P4). The inclusion criteria were presence of symptoms raising suspicion of HF, NTproBNP > 400 pg/mL, and preserved left ventricular function. Exclusion criteria were any type of HF by echocardiography. The outcome was defined as all‐cause mortality. Cox proportional‐hazards regression model was used to investigate the association between the survival time of patients and clinical variables; 1031 patients were identified with NTproBNP > 400 pg/mL but who did not have echocardiographic evidence of HF. All‐cause mortality was 21.5% (222 deaths) over the mean follow‐up (FU) period of 6 ± 2 years. NTproBNP was similar in patients who were alive or dead (P = 0.96). However, age (HR 1, P 627 pg/mL, NYHA class predicted death (II, 19.6%; III, 27.4%; IV, 66.7%; P < 0.01). Conclusions Patients with no HF on echocardiography but raised NTproBNP suffer excess mortality particularly in the presence of certain clinical variables. Age, male gender, worsening CKD stage, presence of COPD, and dementia are independently associated with all‐cause mortality in these patients. An NTproBNP > 627 pg/mL coupled with NYHA class could identify patients at greatest risk of death