Identification of 4-deoxythreonic acid present in human urine using HPLC and NMR techniques

The ¹H NMR spectrum of urine exhibits a large number of detectable and quantifiable metabolites and hence urine metabolite profiling is potentially useful for the study of systems biology and the discovery of biomarkers for drug development or clinical applications. While a number of metabolites (50–100) are readily detectable in urine by NMR, a much larger number is potentially available if lower concentration species can be detected unambiguously. Lower concentration metabolites are thought to be more specific to certain disease states and thus it is important to detect these metabolites with certainty. We report the identification of 4-deoxythreonic acid, a relatively low concentration endogenous metabolite that has not been previously identified in the ¹H NMR spectrum of human urine. The use of HPLC and NMR spectroscopy facilitated the unequivocal and non-invasive identification of the molecule in urine which is complicated by extensive peak overlap and multiple, similar resonances from other metabolites such as 3-hydroxybutanoic acid. High-resolution detection and good sensitivity were achieved by the combination of multiple chromatographic fraction collection, sample pre-concentration, and the use of a cryogenically cooled NMR probe.     

Mefloquine treatment for uncomplicated falciparum malaria in young children 6-24 months of age in northern Ghana

Mefloquine (MQ) single dose 20 mg/kg treatment of falciparum malaria was evaluated in 186 children of 6-24 months of age in northern Ghana. There were 15 RII/RIII-type parasitologic failures, all with Day 2 MQ blood levels significantly lower than children whose parasitemias cleared before Day 7 and remained clear through 28 days. Predictors of RII/RIII parasitologic response were vomiting after MQ dosing, Day 2 MQ levels < 500 ng/mL, and undetectable Day 2 levels of the carboxymefloquine metabolite. There were 50 cases of delayed RI parasitologic failure, but 71% of these cases had undetectable Day 28 blood levels of MQ and drug levels in the remaining 29% ranged below the 620 ng/mL level that suppresses MQ sensitive strains of P. falciparum. Drug levels among infants that tolerated MQ well were not associated with age, weight, hemoglobin, parasitemia, and pre-existing symptoms of vomiting or diarrhea. An observed recurrent parasitemia of 34,400 trophozoites/microL against a MQ blood concentration of 550 ng/mL was taken as indication of tolerance to suppressive levels of the drug at this location.     

Effect of Community-Based Functional Aerobic Training on Motor Performance and Quality of Life of Children with Spastic Cerebral Palsy

BackgroundEfficacies of community-based exercise programmes have been well reported, but there is scarce information on the expediency of community-based rehabilitation in a society where many children with disabilities live in poorly resourced settings with extremely limited rehabilitative services. This study investigated the effects of community-based functional aerobic exercise (CBFAE) on gross motor function, walking distance, and quality of life of children with cerebral palsy (CP).MethodsQuasi-experimental design was used. Children with gross motor function classification system (GMFCS) levels I – II participated in eight weeks CBFAE training four times/week, 50 minutes/day at 40–80% maximum heart rate. Gross motor function (GMF), walking distance and quality of life were assessed pre and post CBFAE training.ResultsSignificant improvement was observed in GMF (Dstanding) (8.2%, P=.000), GMF (E-walking + running+ jumping (5.12%, P=.004), walking distance (6.09%, P=.009). Higher significant positive effects of CBFAE were observed in Social wellbeing and acceptance (107.10%, P=.000), and participation and physical health (105.04%, P=.005) by children parent proxy. Self-reported results showed that for CBFAE, significant positive improvements were higher in pain and impact of disability (67.93%, P=.049) and participation and physical health (60.00%, P=.042).ConclusionCBFAE training contributes majorly to improved standing, walking, jumping and running and self-esteem, quality of life of children with spastic CP. Clinicians and exercise therapists should essentially incorporate CBFAE training and activities into the management of children with CP for improved mobility and functional performances.     

Mucosal delivery of a double-stapled RSV peptide prevents nasopulmonary infection

Respiratory syncytial virus (RSV) infection accounts for approximately 64 million cases of respiratory disease and 200,000 deaths worldwide each year, yet no broadly effective prophylactic or treatment regimen is available. RSV deploys paired, self-associating, heptad repeat domains of its fusion protein, RSV-F, to form a fusogenic 6-helix bundle that enables the virus to penetrate the host cell membrane. Here, we developed hydrocarbon double-stapled RSV fusion peptides that exhibit stabilized α-helical structure and striking proteolytic resistance. Pretreatment with double-stapled RSV peptides that specifically bound to the RSV fusion bundle inhibited infection by both laboratory and clinical RSV isolates in cells and murine infection models. Intranasal delivery of a lead double-stapled RSV peptide effectively prevented viral infection of the nares. A chitosan-based nanoparticle preparation markedly enhanced pulmonary delivery, further preventing progression of RSV infection to the lung. Thus, our results provide a strategy for inhibiting RSV infection by mucosal and endotracheal delivery of double-stapled RSV fusion peptides.     

Evaluation of funding gastroenterology research in Canada illustrates the beneficial role of partnerships

BACKGROUND:

Funders of health research in Canada seek to determine how their funding programs impact research capacity and knowledge creation.

OBJECTIVE:

To evaluate the impact of a focused grants and award program that was cofunded by the Canadian Institutes of Health Research Institute of Nutrition, Metabolism and Diabetes, and the Canadian Association of Gastroenterology; and to measure the impact of the Program on the career paths of funded researchers and assess the outcomes of research supported through the Program.

METHODS:

A survey of the recipients of grants and awards from 2000 to 2008 was conducted in 2012. The CIHR Funding Decisions database was searched to determine subsequent funding; a bibliometric citation analysis of publications arising from the Program was performed.

RESULTS:

Of 160 grant and award recipients, 147 (92%) completed the survey. With >$17.4 million in research funding, support was provided for 131 fellowship awards, seven career transition awards, and 22 operating grants. More than three-quarters of grant and award recipients continue to work or train in a research-related position. Combined research outputs included 545 research articles, 130 review articles, 33 book chapters and 11 patents. Comparative analyses indicate that publications supported by the funding program had a greater impact than other Canadian and international comparators.

CONCLUSIONS:

Continuity in support of a long-term health research funding partnership strengthened the career development of gastroenterology researchers in Canada, and enhanced the creation and dissemination of new knowledge in the discipline.     

Central Retinal Enrichment Supplementation Trials (CREST): Design and Methodology of the CREST Randomized Controlled Trials

Abstract

Purpose: The Central Retinal Enrichment Supplementation Trials (CREST) aim to investigate the potential impact of macular pigment (MP) enrichment, following supplementation with a formulation containing 10?mg lutein (L), 2?mg zeaxanthin (Z) and 10?mg meso-zeaxanthin (MZ), on visual function in normal subjects (Trial 1) and in subjects with early age-related macular degeneration (AMD; Trial 2).

Methods: CREST is a single center, double-blind, randomized clinical trial. Trial 1 (12-month follow-up) subjects are randomly assigned to a formulation containing 10?mg?L, 10?mg MZ and 2?mg Z (n?=?60) or placebo (n?=?60). Trial 2 (24-month follow-up) subjects are randomly assigned to a formulation containing 10?mg?L, 10?mg MZ, 2?mg Z plus 500?mg vitamin C, 400?IU vitamin E, 25?mg zinc and 2?mg copper (Intervention A; n?=?75) or 10?mg?L and 2?mg Z plus 500?mg vitamin C, 400?IU vitamin E, 25?mg zinc and 2?mg copper (Intervention B; n?=?75). Contrast sensitivity (CS) at 6 cycles per degree represents the primary outcome measure in each trial. Secondary outcomes include: CS at other spatial frequencies, MP, best-corrected visual acuity, glare disability, photostress recovery, light scatter, cognitive function, foveal architecture, serum carotenoid concentrations, and subjective visual function. For Trial 2, AMD morphology, reading speed and reading acuity are also being recorded.

Conclusions: CREST is the first study to investigate the impact of supplementation with all three macular carotenoids in the context of a large, double-blind, randomized clinical trial.     

Challenges in linking health research to policy: a commentary on developing a multi-stakeholder response to orphans and vulnerable children in Ghana

The Research and Development Division (RDD) of the Ghana Health Service (GHS) has a remit to build research capacity and conduct policy relevant research. By being situated within the GHS, RDD has good access to directors and programme managers, within and beyond the Ministry of Health. This structure has been facilitating collaboration through research cycles for 20 years, from agenda setting to discussions on policy relevance.This approach has been applied to research activities within the Addressing the Balance of Burden in AIDS (ABBA) Research Programme Consortium to tackle the challenges facing HIV affected orphans and vulnerable children (OVCs). The government strategy on OVCs recommends they should be encouraged to live in their home communities rather than in institutions. We present lessons here on efforts to use research to build a response across different agencies to address the problems that communities and families face in caring for these children in their communities.This approach to building consensus on research priorities points to the value of collaboration and dialogue with multiple stakeholders as a means of fostering ownership of a research process and supporting the relevance of research to different groups. Our experience has shown that if the context within which researchers, policy makers and stakeholders work were better understood, the links between them were improved and research were communicated more effectively, then better policy making which links across different sectors may follow. At the same time, collaboration among these different stakeholders to ensure that research meets social needs, must also satisfy the requirements of scientific rigour.     

Comparison of glucagon-like peptide-1 receptor (GLP-1R) PET/CT,SPECT/CT and 3T MRI for the localisation of occult insulinomas: evaluation of diagnostic accuracy in a prospective crossover imaging study

Purpose

Benign insulinomas are the most prevalent cause of endogenous hyperinsulinaemic hypoglycaemia (EHH) in adults, and because of their small size are difficult to localise. The purpose of the study was to test the diagnostic accuracy and clinical impact of glucagon-like peptide-1 receptor (GLP-1R) PET/CT using ⁶⁸Ga-DOTA-exendin-4 in consecutive adult patients referred for localisation of insulinomas. The results were compared with ¹¹¹In-DOTA-exendin-4 SPECT/CT, study-MRI and previously performed external CT and/or MRI (prior external CT/MRI).

Methods

We prospectively enrolled patients with neuroglycopenic symptoms due to EHH. GLP-1R PET/CT, SPECT/CT and study-MRI were performed in a randomised, crossover order within 3–4 days. The reference standard was surgery with histology and treatment outcome.

Results

From January 2014 until March 2017, 52 patients were recruited. All imaging and invasive procedures before recruitment identified suspicious lesions in 46.2% of patients. GLP-1R PET/CT, SPECT/CT and study-MRI detected suspicious lesions in 78.8%, 63.5% and 63.4% of patients, respectively. In 38 patients, conclusive histology was available for final analysis.Accuracy (95% confidence interval) for PET/CT, SPECT/CT, study-MRI and prior external CT/MRI was 93.9% (87.8–97.5%), 67.5% (58.1–76.0%), 67.6% (58.0–76.1%) and 40.0% (23.9–57.9%), respectively (all P values < 0.01, except comparison of SPECT/CT and study-MRI with a P value?=?1.0). Impact on clinical management was 42.3%, 32.7% and 33.3% for PET/CT, SPECT/CT and study-MRI, respectively. Percentage reading agreement was 89.5%, 75.7%, and 71.1% for PET/CT, SPECT/CT and study-MRI, respectively.

Conclusion

⁶⁸Ga-DOTA-exendin-4 PET/CT performed significantly better than ¹¹¹In-DOTA-exendin-4 SPECT/CT and MRI in the localisation of benign insulinomas and should be considered in patients where localisation fails with CT/MRI (ClinicalTrials.gov, NCT02127541).

     

Indication of Risk of Mother-to-Child <Emphasis Type="Italic">Toxoplasma gondii</Emphasis> Transmission in the Greater Accra Region of Ghana

Objectives Congenital infection with Toxoplasma gondii is known to result in neurological and brain disorders including ophthalmic disorders later in life. Research in Ghana revealed high sero-prevalence among pregnant women and eye patients. This study determines the risk of congenital transmission of T. gondii infection in Accra, Ghana. Methods One hundred consented pregnant women aged 18–45 years (mean 29.85 ± 5.76) participated. Venous blood and tissue samples were taken from the maternal side of each placenta after delivery. Cord blood samples were also taken after they were separated from the infants. Finger-prick blood was taken from infants of participating women at 2 or 6 weeks post-natal. ELISA was used to detect T. gondii antibodies in all blood samples while Nested-PCR was used to detect T. gondii DNA from placental tissues. Data was analysed using SPSS v. 16. Results Overall, 37.6 % of maternal blood, 39.5 % of umbilical cord blood, and 57.5 % of post-natal infant blood were positive for anti-T. gondii IgG. No anti-T. gondii IgM was detected in any of those samples. Toxoplasma gondii DNA was detected in 39.8 % of placental tissue samples. Strong association was observed in the occurrence of placental T. gondii DNA and anti-T. gondii IgG positive women (ø = 0.810, p < 0.00001) as well as high Relative risk shown in the likelihood of foetal exposure to infection in latently-infected women (RR 10.39; CI 4.47–24.17; p < 0.00001). Conclusions for Practice The presence of anti-T. gondii IgG antibodies only, and T. gondii DNA in placental tissues indicate the women might have been infected early during the pregnancy, placing about 39.8 % of the babies at risk. These results can strongly influence policy to screen and treat pregnant women for T. gondii infection.