Determination of sodium fatty acid in soap Formulation Using Fourier Transform Infrared (FTIR) spectroscopy and multivariate calibrations.

Fourier Transform Infrared (FTIR) spectroscopy using an attenuated total reflectance (ATR) accessory has been investigated as a method for the determination of sodium-fatty acid (sodium-FA) in soap formulations. Multivariate calibrations namely partial least squares regression (PLS) and principle component regression (PCR) were developed for the prediction of sodium-FA using spectral ranges on the basis of relevant IR absorption bands related to sodium-FA. The sodium-FA content in soap formulations was predicted accurately at wavenumbers of 1,570–1,550 cm−1, which is specific for RCOO− Na+ vibration. The PLS method was found to be a consistently better predictor when both PLS and principal component regression (PCR) analyses were used for quantification of sodium-FA. Furthermore, FTIR spectroscopy can be an alternative technique to American oil Chemist Society methods which use a titrimetric technique because FTIR offers rapid, easy sample preparation and is friendly to the environment

Inducing remission of Type 2 diabetes in the Caribbean: findings from a mixed methods feasibility study of a low-calorie liquid diet-based intervention in Barbados.

AIM: In a high proportion of people with recently diagnosed Type 2 diabetes, a short (2-3-month) low-calorie diet is able to restore normal glucose and insulin metabolism. The aim of this study was to determine the feasibility of this approach in Barbados. METHODS: Twenty-five individuals with Type 2 diabetes diagnosed within past 6 years, not on insulin, BMI ≥ 27 kg/m2 were recruited. Hypoglycaemic medication was stopped on commencement of the 8-week liquid (760 calorie) diet. Insulin response was assessed in meal tests at baseline, 8 weeks and 8 months. Semi-structured interviews, analysed thematically, explored participants' experiences. 'Responders' were those with fasting plasma glucose (FPG) < 7 mmol/l at 8 weeks. RESULTS: Ten men and 15 women (mean age 48, range 26-68 years) participated. Mean (sd) BMI was 34.2 kg/m2 (6.0); FPG 9.2 mmol/l (2.2). Mean weight loss at 8 weeks and 8 months was 10.1 kg [95% confidence interval (CI) 8.1, 12.0] and 8.2 kg (95% CI 5.8, 10.6); FPG was lower by 2.2 mmol/l (95% CI 1.2, 3.2) and 1.7 mmol/l (95% CI 0.8, 2.7) respectively. Nine of 11 (82%) of those who lost ≥ 10 kg were 'responders' compared with 6 of 14 (43%) who lost < 10 kg (P = 0.048). The 30-min insulin increment was higher in responders at baseline and follow-up (P ≤ 0.01). A food culture based on starchy foods and pressures to eat large amounts at social events were among the challenges identified by participants. CONCLUSIONS: The feasibility of this approach to weight loss and diabetes remission in a predominantly black population in Barbados was demonstrated

Intestinal Microbiota Shifts towards Elevated Commensal Escherichia coli Loads Abrogate Colonization Resistance against Campylobacter jejuni in Mice

Background: The zoonotic pathogen Campylobacter jejuni is a leading cause of bacterial foodborne enterocolitis in humans worldwide. The understanding of immunopathology underlying human campylobacteriosis is hampered by the fact that mice display strong colonization resistance against the pathogen due to their host specific gut microbiota composition. Methodology/Principal Findings: Since the microbiota composition changes significantly during intestinal inflammation we dissected factors contributing to colonization resistance against C. jejuni in murine ileitis, colitis and in infant mice. In contrast to healthy animals C. jejuni could stably colonize mice suffering from intestinal inflammation. Strikingly, in mice with Toxoplasma gondii-induced acute ileitis, C. jejuni disseminated to mesenteric lymphnodes, spleen, liver, kidney, and blood. In infant mice C. jejuni infection induced enterocolitis. Mice suffering from intestinal inflammation and C. jejuni susceptible infant mice displayed characteristical microbiota shifts dominated by increased numbers of commensal Escherichia coli. To further dissect the pivotal role of those distinct microbiota shifts in abrogating colonization resistance, we investigated C. jejuni infection in healthy adult mice in which the microbiota was artificially modified by feeding live commensal E. coli. Strikingly, in animals harboring supra-physiological intestinal E. coli loads, colonization resistance was significantly diminished and C. jejuni infection induced enterocolitis mimicking key features of human campylobacteriosis. Conclusion/Significance: Murine colonization resistance against C. jejuni is abrogated by changes in the microbiot

Compensated right ventricular function of the onset of pulmonary hypertension in a rat model depends on chamber remodeling and contractile augmentation.

Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geometric remodeling and intrinsic changes in myocardial mechanical properties in a monocrotaline (MCT) animal model. In a longitudinal study of PAH, ventricular morphology and function were assessed weekly during the first four weeks after MCT exposure. Using invasive measurements of RV pressure and volume, heart performance was evaluated at end of systole and diastole to quantify contractility (end-systolic elastance) and chamber stiffness (end-diastolic elastance). To distinguish between morphological and intrinsic mechanisms, a computational model of the RV was developed and used to determine the level of prediction when accounting for wall masses and unloaded volume measurements changes. By four weeks, mean pulmonary arterial pressure and elastance rose significantly. RV pressures rose significantly after the second week accompanied by significant RV hypertrophy, but RV stroke volume and cardiac output were maintained. The model analysis suggested that, after two weeks, this compensation was only possible due to a significant increase in the intrinsic inotropy of RV myocardium. We conclude that this MCT-PAH rat is a model of RV compensation during the first month after treatment, where geometric remodeling on EDPVR and increased myocardial contractility on ESPVR are the major mechanisms by which stroke volume is preserved in the setting of elevated pulmonary arterial pressure. The mediators of this compensation might themselves promote longer-term adverse remodeling and decompensation in this animal model

Identification of a novel heterozygous guanosine monophosphate reductase (GMPR) variant in a patient with a late-onset disorder of mitochondrial DNA maintenance

Autosomal dominant progressive external ophthalmoplegia (adPEO) is a late-onset, Mendelian mitochondrial disorder characterised by paresis of the extraocular muscles, ptosis and skeletal-muscle restricted multiple mitochondrial DNA (mtDNA) deletions. While dominantly-inherited, pathogenic variants in POLG, TWNK and RRM2B are among the most common genetic defects of adPEO, identification of novel candidate genes and the underlying pathomechanisms remain challenging. We report the clinical, genetic and molecular investigations of a patient who presented in the seventh decade of life with PEO. Oxidative histochemistry revealed cytochrome c oxidase deficient fibres and occasional ragged red fibres showing subsarcolemmal mitochondrial accumulation in skeletal muscle, while molecular studies identified the presence of multiple mtDNA deletions. Negative candidate screening of known nuclear genes associated with PEO prompted diagnostic exome sequencing, leading to the prioritisation of a novel heterozygous c.547G > C variant in GMPR (NM_006877.3) encoding guanosine monophosphate reductase, a cytosolic enzyme required for maintaining the cellular balance of adenine and guanine nucleotides. We show that the novel c.547G > C variant causes aberrant splicing, decreased GMPR protein levels in patient skeletal muscle, proliferating and quiescent cells and is associated with subtle changes in nucleotide homeostasis protein levels and evidence of disturbed mtDNA maintenance in skeletal muscle. Despite confirmation of GMPR deficiency, demonstrating marked defects of mtDNA replication or nucleotide homeostasis in patient cells proved challenging. Our study proposes that GMPR is the nineteenth (19th) locus for PEO and highlights the complexities of uncovering disease mechanisms in late-onset PEO phenotypes

Nonequilibrium Dynamics in Noncommutative Spacetime

We study the effects of spacetime noncommutativity on the nonequilibrium dynamics of particles in a thermal bath. We show that the noncommutative thermal bath does not suffer from any further IR/UV mixing problem in the sense that all the finite-temperature non-planar quantities are free from infrared singularities. We also point out that the combined effect of finite temperature and noncommutative geometry has a distinct effect on the nonequilibrium dynamics of particles propagating in a thermal bath: depending on the momentum of the mode of concern, noncommutative geometry may switch on or switch off their decay and thermalization. This momentum dependent alternation of the decay and thermalization rates could have significant impacts on the nonequilibrium phenomena in the early universe at which spacetime noncommutativity may be present. Our results suggest a re-examination of some of the important processes in the early universe such as reheating after inflation, baryogenesis and the freeze-out of superheavy dark matter candidates.Comment: 24 pages, 2 figure

Haplotype Analysis Reveals a Possible Founder Effect of RET Mutation R114H for Hirschsprung's Disease in the Chinese Population

Background Hirschsprung's disease (HSCR) is a congenital disorder associated with the lack of intramural ganglion cells in the myenteric and sub-mucosal plexuses along varying segments of the gastrointestinal tract. The RET gene is the major gene implicated in this gastrointestinal disease. A highly recurrent mutation in RET (RETR114H) has recently been identified in ~6-7% of the Chinese HSCR patients which, to date, has not been found in Caucasian patients or controls nor in Chinese controls. Due to the high frequency of RETR114H in this population, we sought to investigate whether this mutation may be a founder HSCR mutation in the Chinese population. Methodology and Principal Findings To test whether all RETR114H were originated from a single mutational event, we predicted the approximate age of RETR114H by applying a Bayesian method to RET SNPs genotyped in 430 Chinese HSCR patients (of whom 25 individuals had the mutation) to be between 4-23 generations old depending on growth rate. We reasoned that if RETR114H was a founder mutation then those with the mutation would share a haplotype on which the mutation resides. Including SNPs spanning 509.31 kb across RET from a recently obtained 500 K genome-wide dataset for a subset of 181 patients (14 RETR114H patients), we applied haplotype estimation methods to determine whether there were any segments shared between patients with RETR114H that are not present in those without the mutation or controls. Analysis yielded a 250.2 kb (51 SNP) shared segment over the RET gene (and downstream) in only those patients with the mutation with no similar segments found among other patients. Conclusions This suggests that RETR114H is a founder mutation for HSCR in the Chinese population. © 2010 Cornes et al.published_or_final_versio

Analysis of dental care of children receiving comprehensive care under general anaesthesia at a teaching hospital in England

Objectives: This study aimed to analyse the characteristics of comprehensive dental care provided under general anaesthesia (CDGA) and to review the additional treatment required by children over the 6 years subsequent to CDGA. Method: Information collected from hospital records for the 6-year period following the first CDGA included the types of dental treatment performed at CDGA, the return rates for follow-up appointments, further treatment required subsequent to CDGA and the types of dental treatment performed at repeat DGA. Results: The study population consisted of 263 children, of whom 129 had a significant medical history, with mean age of 6.7 years. The results revealed that the waiting time for CDGA was significantly shorter in children who had a significant medical history, with 49 % being admitted for CDGA within 3 months of pre-GA assessment, as compared to 29 % of healthy children. 67 % of children had follow-up care recorded, with a slightly higher proportion of children with significant medical history returning for follow-up [70 % (90/129)] compared with 65 % (87/134) of healthy children. Re-treatment rates were 34 % (88/263), the majority of cases being treated under local analgesia (42/88). 34 of 263 children had repeat DGA (12.9 %). Of these 71 % (24/34) were children with significant medical history. The mean age at repeat DGA was 9 years. In 25 of 34 children (74 %), repeat DGA was due to trauma, oral pathology, supernumerary removal, hypomineralized teeth or new caries of previously sound or un-erupted teeth at CDGA. The ratio of extraction over restoration (excluding fissure sealants) performed at repeat DGA was 2.8, compared with the ratio of 1.3 in the initial CDGA. Conclusions: There was a higher ratio of extraction over restorations at the repeat DGA. This suggests that the prescribed treatments at repeat DGA were more aggressive as compared to the initial CDGA in 1997. The majority of the treatment required at repeat DGA was to treat new disease

Fine Mapping of the NRG1 Hirschsprung's Disease Locus

The primary pathology of Hirschsprung's disease (HSCR, colon aganglionosis) is the absence of ganglia in variable lengths of the hindgut, resulting in functional obstruction. HSCR is attributed to a failure of migration of the enteric ganglion precursors along the developing gut. RET is a key regulator of the development of the enteric nervous system (ENS) and the major HSCR-causing gene. Yet the reduced penetrance of RET DNA HSCR-associated variants together with the phenotypic variability suggest the involvement of additional genes in the disease. Through a genome-wide association study, we uncovered a ∼350 kb HSCR-associated region encompassing part of the neuregulin-1 gene (NRG1). To identify the causal NRG1 variants contributing to HSCR, we genotyped 243 SNPs variants on 343 ethnic Chinese HSCR patients and 359 controls. Genotype analysis coupled with imputation narrowed down the HSCR-associated region to 21 kb, with four of the most associated SNPs (rs10088313, rs10094655, rs4624987, and rs3884552) mapping to the NRG1 promoter. We investigated whether there was correlation between the genotype at the rs10088313 locus and the amount of NRG1 expressed in human gut tissues (40 patients and 21 controls) and found differences in expression as a function of genotype. We also found significant differences in NRG1 expression levels between diseased and control individuals bearing the same rs10088313 risk genotype. This indicates that the effects of NRG1 common variants are likely to depend on other alleles or epigenetic factors present in the patients and would account for the variability in the genetic predisposition to HSCR