Global Patterns in Overweight Among Children and Mothers in Less Developed Countries

Objective: Past research has identified increases in national income and urbanization as key drivers of the global obesity epidemic. That work further identified educational attainment and urban residence as important moderators of the effects of national income. However, such work has tended to assume that children and adults respond in the same way to these factors. In the present paper, we evaluate how the socio-economic and country-level factors associated with obesity differ between children and their mothers. Design: We modelled the associations between maternal education, country-level income and urban residence with mother\u27s and children\u27s weight status. Setting We analysed ninety-five nationally representative health and nutrition surveys conducted between 1990 and 2008 from thirty-three less developed countries. Subjects Our sample included children aged 2-4 years (n 253 442) and their mothers (n 228 655). Results Consistent with prior research, we found that mothers\u27 risk of overweight was positively associated with economic development, urban residence and maternal education. Additionally, economic development was associated with steeper increases in mothers\u27 risk of overweight among those with low (v. high) levels of education and among those living in rural (v. urban) areas. However, these associations were different for children. Child overweight was not associated with maternal education and urban residence, and negatively associated with national income. Conclusions: We speculate that the distinctive patterns for children may arise from conditions in low- and middle-income developing countries that increase the risk of child underweight and poor nutrition. © The Authors 2012

Co-production of 11α-hydroxyprogesterone and ethanol using recombinant yeast expressing fungal steroid hydroxylases

Background Bioethanol production from sustainable sources of biomass that limit effect on food production are needed and in a biorefinery approach co-products are desirable, obtained from both the plant material and from the microbial biomass. Fungal biotransformation of steroids was among the first industrial biotransformations allowing corticosteroid production. In this work, the potential of yeast to produce intermediates needed in corticosteroid production is demonstrated at laboratory scale following bioethanol production from perennial ryegrass juice. Results Genes encoding the 11?-steroid hydroxylase enzymes from Aspergillus ochraceus (11?-SHAoch) and Rhizopus oryzae (CYP509C12) transformed into Saccharomyces cerevisiae for heterologous constitutive expression in p425TEF. Both recombinant yeasts (AH22:p11?-SHAoch and AH22:p509C12) exhibited efficient progesterone bioconversion (on glucose minimal medial containing 300 ?M progesterone) producing either 11?-hydroxyprogesterone as the sole metabolite (AH22:p11?-SHAoch) or a 7:1 mixture of 11?-hydroxyprogesterone and 6?-hydroxyprogesterone (AH22:p509C12). Ethanol yields for AH22:p11?-SHAoch and AH22:p509C12 were comparable resulting in ?75% conversion of glucose to alcohol. Co-production of bioethanol together with efficient production of the 11-OH intermediate for corticosteroid manufacture was then demonstrated using perennial ryegrass juice. Integration of the 11?-SHAoch gene into the yeast genome (AH22:11?-SHAoch+K) resulted in a 36% reduction in yield of 11?-hydroxyprogesterone to 174 ?mol/L using 300 ?M progesterone. However, increasing progesterone concentration to 955 ?M and optimizing growth conditions increased 11?-hydroxyprogesterone production to 592 ?mol/L product formed. Conclusions The progesterone 11?-steroid hydroxylases from A. ochraceus and R. oryzae, both monooxygenase enzymes of the cytochrome P450 superfamily, have been functionally expressed in S. cerevisiae. It appears that these activities in fungi are not associated with a conserved family of cytochromes P450. The activity of the A. ochraceous enzyme was important as the specificity of the biotransformation yielded just the 11-OH product needed for corticosteroid production. The data presented demonstrate how recombinant yeast could find application in rural biorefinery processes where co-production of value-added products (11?-hydroxyprogesterone and ethanol) from novel feedstocks is an emergent and attractive possibility.publishersversionPeer reviewe

Yoga for Adults with Intellectual and Developmental Disabilities: A Pilot Study

Intellectual and developmental disabilities (IDD) include diagnoses such as autism spectrum disorder (ASD), Down syndrome (DS), and fragile X syndrome (FXS). Generally, individuals with IDD have an increased risk of experiencing poor functional fitness compared to adults without IDD, which can lead to an increased rate of health deterioration and reduced ability to complete activities of daily living. Functional fitness might be positively impacted by yoga, which is an ancient mind-body practice that that synchronously uses controlled breath practices, mindfulness, and physical postures. Yoga has generally been demonstrated to be effective for improving functional fitness for adults, both with and without disability. Little research, however, has been done regarding yoga for individuals with IDD. This single-arm pilot study measured pre and post test functional fitness after a yoga intervention delivered for 60-minutes twice a week for six weeks in a special population recreation center for people with IDD. Eligible individuals completed a battery of functional fitness physical performance measures. A team of yoga teachers and a yoga therapist developed a standardized intervention protocol to promote improving muscular strength and balance. Each yoga session included a standardized progression of postures, breath work, and guided meditation, and affirmations called “mantras” (e.g. I am strong, I am loved). Multiple modifications were offered for engaging in postures including participating from a chair. Each session ended with a four-minute relaxation pose. Pre- and posttest scores were compared using a Wilcoxon Signed Rank test and were further examined with a percent change calculation (Time 1-Time 2/Time 1 * 100). Nine participants assented and completed pre and post-testing. There was a significant improvement in three of the six functional fitness measures. This intervention study indicates positive outcomes to promote functional fitness among individuals with IDD. The preliminary significant results indicate that a yoga intervention may have the potential to enhance functional fitness in people with IDD

Small‐Molecule Inhibitors Targeting Sterol 14α‐Demethylase (CYP51): Synthesis, Molecular Modelling and Evaluation Against Candida albicans

Fungal infections are a global issue affecting over 150 million people worldwide annually, with 750 000 of these caused by invasive Candida infections. Azole drugs are the frontline treatment against fungal infections; however, resistance to current azole antifungals in C. albicans poses a threat to public health. Two series of novel azole derivatives, short and extended derivatives, have been designed, synthesised and investigated for CYP51 inhibitory activity, binding affinity and minimum inhibitory concentration (MIC) against C. albicans strains. The short derivatives were more potent against the C. albicans strains (e. g., MIC 2‐(4‐chlorophenyl)‐N‐(2,4‐dichlorobenzyl)‐3‐(1H‐imidazol‐1‐yl)propanamide (5 f ) <0.03 μg/mL, N‐(4‐((4‐chlorophenyl)sulfonamido)benzyl)‐2‐phenyl‐3‐(1H‐1,2,4‐triazol‐1‐yl)propanamide (12 c ), 1 μg/mL, fluconazole 0.125 μg/mL) but both displayed comparable enzyme binding and inhibition (5 f K d 62±17 nM, IC50 0.46 μM; 12 c K d 43±18 nM, IC50 0.33 μM, fluconazole K d 41±13 nM, IC50 0.31 μM, posaconazole K d 43±11 nM, IC50 0.2 μM). The short series had poor selectivity for CaCYP51 over the human homologue, whereas the selectivity of the extended series, for example, compound 12 c , was higher (21.5‐fold) than posaconazole (4.7‐fold) based on K d values, although posaconazole was more selective (615‐fold) than 12 c (461‐fold) based on IC50 values. Based on inhibitory activity and selectivity profile, the extended series are the better of the two series for further development

Neonatal desensitisation for the study of regenerative medicine

Cell replacement is a therapeutic option for numerous diseases of the CNS. Current research has identified a number of potential human donor cell types, for which preclinical testing through xenotransplantation in animal models is imperative. Immune modulation is necessary to promote donor cell survival for sufficient time to assess safety and efficacy. Neonatal desensitization can promote survival of human donor cells in adult rat hosts with little impact on the health of the host and for substantially longer than conventional methods, and has subsequently been applied in a range of studies with variable outcomes. Reviewing these findings may provide insight into the method and its potential for use in preclinical studies in regenerative medicine

Imaging functional recovery following ischemic stroke: clinical and preclinical fMRI studies

Disability and effectiveness of physical therapy are highly variable following ischemic stroke due to different brain regions being affected. Functional magnetic resonance imaging (fMRI) studies of patients in the months and years following stroke have given some insight into how the brain recovers lost functions. Initially, new pathways are recruited to compensate for the lost region, showing as a brighter BOLD signal over a larger area during a task than in healthy controls. Subsequently, activity is reduced to baseline levels as pathways become more efficient, mimicking the process of learning typically seen during development. Preclinical models of ischemic stroke aim to enhance understanding of the biology underlying recovery following stroke. However, the pattern of recruitment and focusing seen in humans has not been observed in preclinical fMRI studies which are highly variable methodologically. Resting-state fMRI studies show more consistency, however there are still confounding factors to address. Anaesthesia and method of stroke induction are the two main sources of variability in preclinical studies; improvements here can reduce variability and increase the intensity and reproducibility of the BOLD response detected by fMRI. Differences in task or stimulus, and differences in analysis method also present a source of variability. This review compares clinical and preclinical fMRI studies of recovery following stroke and focuses on how refinement of preclinical models and MRI methods may obtain more representative fMRI data in relation to human studies

The Investigational Drug VT-1129 Is a Highly Potent Inhibitor of Cryptococcus Species CYP51 but Only Weakly Inhibits the Human Enzyme

Cryptococcosis is a life-threatening disease often associated with HIV infection. Three Cryptococcus species CYP51 enzymes were purified and catalyzed the 14α-demethylation of lanosterol, eburicol, and obtusifoliol. The investigational agent VT-1129 bound tightly to all three CYP51 proteins (dissociation constant [K(d)] range, 14 to 25 nM) with affinities similar to those of fluconazole, voriconazole, itraconazole, clotrimazole, and ketoconazole (K(d) range, 4 to 52 nM), whereas VT-1129 bound weakly to human CYP51 (K(d), 4.53 μM). VT-1129 was as effective as conventional triazole antifungal drugs at inhibiting cryptococcal CYP51 activity (50% inhibitory concentration [IC(50)] range, 0.14 to 0.20 μM), while it only weakly inhibited human CYP51 activity (IC(50), ∼600 μM). Furthermore, VT-1129 weakly inhibited human CYP2C9, CYP2C19, and CYP3A4, suggesting a low drug-drug interaction potential. Finally, the cellular mode of action for VT-1129 was confirmed to be CYP51 inhibition, resulting in the depletion of ergosterol and ergosta-7-enol and the accumulation of eburicol, obtusifolione, and lanosterol/obtusifoliol in the cell membranes

Facile silane functionalization of graphene oxide

The facile silane functionalization of graphene oxide (GO) was achieved yielding vinyltrimethoxysilane-reduced graphene oxide (VTMOS-rGO) nanospheres located in the inter-layer spacing between rGO sheets via an acid–base reaction using aqueous media. The successful grafting of the silane agent with pendant vinyl groups to rGO was confirmed by a combination of Fourier-transform infrared (FTIR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The structure and speciation of the silane-graphene network (nanosphere) and, the presence of free vinyl groups was verified from solid-state magic angle spinning (MAS) and solution 13C and 29Si nuclear magnetic resonance (NMR) measurements. Evidence from Scanning Electron Microscopy (SEM), High-Resolution Transmission Electron Microscopy (HRTEM) and TEM-High-Angle Annular Dark-Field (TEM-HAADF) imaging showed that these silane networks aided the exfoliation of the rGO layers preventing agglomeration, the interlayer spacing increased by 10 Å. The thermal stability (TGA/DTA) of VTMOS-rGO was significantly improved relative to GO, displaying just one degradation process for the silane network some 300 °C higher than either VTMOS or GO alone. The reduction of GO to VTMOS-rGO induced sp2 hybridization and enhanced the electrical conductivity of GO by 105 S m−1

Identification of Klebsiella capsule synthesis loci from whole genome data.

Klebsiella pneumoniae is a growing cause of healthcare-associated infections for which multi-drug resistance is a concern. Its polysaccharide capsule is a major virulence determinant and epidemiological marker. However, little is known about capsule epidemiology since serological typing is not widely accessible and many isolates are serologically non-typeable. Molecular typing techniques provide useful insights, but existing methods fail to take full advantage of the information in whole genome sequences. We investigated the diversity of the capsule synthesis loci (K-loci) among 2503 K. pneumoniae genomes. We incorporated analyses of full-length K-locus nucleotide sequences and also clustered protein-encoding sequences to identify, annotate and compare K-locus structures. We propose a standardized nomenclature for K-loci and present a curated reference database. A total of 134 distinct K-loci were identified, including 31 novel types. Comparative analyses indicated 508 unique protein-encoding gene clusters that appear to reassort via homologous recombination. Extensive intra- and inter-locus nucleotide diversity was detected among the wzi and wzc genes, indicating that current molecular typing schemes based on these genes are inadequate. As a solution, we introduce Kaptive, a novel software tool that automates the process of identifying K-loci based on full locus information extracted from whole genome sequences (https://github.com/katholt/Kaptive). This work highlights the extensive diversity of Klebsiella K-loci and the proteins that they encode. The nomenclature, reference database and novel typing method presented here will become essential resources for genomic surveillance and epidemiological investigations of this pathogen