A periosteum-derived cell line to study the role of BMP/TGFß signaling in periosteal cell behavior and function.

The periosteum is a thin tissue surrounding each skeletal element that contains stem and progenitor cells involved in bone development, postnatal appositional bone growth, load-induced bone formation, and fracture repair. BMP and TGFß signaling are important for periosteal activity and periosteal cell behavior, but thorough examination of the influence of these pathways on specific cell populations resident in the periosteum is lacking due to limitations associated with primary periosteal cell isolations and in vitro experiments. Here we describe the generation of a novel periosteum-derived clonal cell (PDC) line from postnatal day 14 mice and use it to examine periosteal cell behavior in vitro. PDCs exhibit key characteristics of periosteal cells observed during skeletal development, maintenance, and bone repair. Specifically, PDCs express established periosteal markers, can be expanded in culture, demonstrate the ability to differentiate into chondrocytes, osteoblasts, and adipocytes, and exhibit an osteogenic response to physical stimulation. PDCs also engage in BMP and/or TGFß signaling when treated with the activating ligands BMP2 and TGFß-1, and in response to mechanical stimulation via fluid shear. We believe that this PDC line will be useful for large-scale, long-term experiments that were not feasible when using primary periosteal cells. Anticipated future uses include advancing our understanding of the signaling interactions that occur during appositional bone growth and fracture repair and developing drug screening platforms to discover novel growth and fracture healing factors.

Visual impairment and perceptual visual disorders in children with cerebral palsy in Nigeria.

Cerebral palsy (CP) is the most common cause of childhood physical disability globally. This study describes the spectrum of ocular morbidity and visual impairment in a community-based (recruited by key informants) sample of children with CP in Cross River State, Nigeria. METHODS: A paediatric neurologist clinically confirmed CP and assessed systemic comorbidity. Ophthalmological assessment included developmental age appropriate acuity tests, objective refraction and objective and subjective tests of perceptual visual dysfunction (PVD). RESULTS: 388 children aged 4-15 years with CP were identified. Visual problems were reported by carers in only 55 (14%) cases. Binocular visual acuity impairment was seen in 20/201 by Lea symbols test (10%) and 213/388 (55%) by the mirror test. Abnormal visual fields were seen in 58/388 (14.9%); strabismus in 183 (47%) abnormal contrast sensitivity in 178 (46%) and abnormal saccades in 84 (22%), spherical refractive errors in 223 (58%), significant astigmatism in 36 (12%), accommodative dysfunction in 41 (10.6%), optic atrophy in 198 (51%). Perceptual visual disorders were present in 22 (6%) subjectively and 177 (46%) objectively. The estimated frequency of cerebral visual impairment (CVI) in children ranged from 61 (16%) to 191 (49%) if children with optic atrophy were included. CONCLUSION: Children with CP have a wide spectrum of ocular morbidity and visual impairment, underestimated by carers. Children with CP require visual acuity assessments with a range of tests which account for associated comorbidities and oculomotor dysfunction. Functional vision assessments for PVD is important. CVI is common.

The Effect of Insight Questions Inventory and Visual Support Strategies on Carer-Reported Quality of Life for Children With Cerebral Palsy and Perceptual Visual Dysfunction in Nigeria: A Randomized Controlled Trial.

Structured clinical history question inventories have previously been used to try and elicit symptoms of perceptual visual dysfunction (PVD) in children with cerebral palsy (CP) in different settings. Earlier studies have suggested that PVD may affect quality of life and specific habilitational strategies, linked to inventory responses, may improve quality of life. Through an RCT, based on a community based sample of children with CP in Cross River State, Nigeria, we aimed to determine if a structured history inventory such as the Insight question inventory (IQI) and associated tailored visual support strategies (IQI VSS) for the management of those children who have PVD, can improve quality of life and is superior to standard therapy. Children with CP were recruited by the key informant method and confirmed by clinical examination. The parent reported IQI was used to identify children with PVD. Primary outcome measures were both Pediatric Quality of Life 4.0 Generic (PedsQL 4.0 Generic) and Pediatric Quality of Life 3.0 Cerebral Palsy (PedsQL 3.0 CP) scale scores. Children were enrolled with a parallel arm allocation to either IQI and IQI VSS or to standard therapy for CP. Children were followed up for 6 weeks with weekly phone call session and the questionnaires repeated at the end of the 6 weeks' period. Results show that the children in the treatment group (n = 191) showed no significantly different change between baseline and follow up in quality of life (PedsQL 4.0 Generic p = 0.943: and PedsQL-CP 3.0 p = 0.287), compared to the control group. There was suggestion of a better improvement (p = 0.035) in the PedsQL 3.0 CP subscale of speech and communication for the intervention group. The use of IQI VSS for the treatment of PVD in children with CP in this population does not show any superiority over current standard CP management in terms of overall quality of life. However, there was some evidence of improvement in quality of life in the area of speech and communication. Further research and refinement of these management method is required. Clinical Trial Registration: www.ClinicalTrials.gov, identifier [PACTR20161200188] 6396.

Pattern of comorbidities in school-aged children with cerebral palsy in Cross River State, Nigeria.

BACKGROUND: To describe the pattern of comorbidities in school-aged children with cerebral palsy (CP) and to identify which, if any, were associated with poor school attendance. A cross-sectional study, using the key informant methodology, between December 2017 and July 2018 was conducted in Cross River State, Nigeria. Assessments, confirmation of CP and identification of systemic comorbidities using standard tools and questionnaires were performed. Children confirmed to have CP between the ages 4 to 15 years were included. RESULTS: Three hundred and eighty-eight children were confirmed to have CP, 59% males. The mean age was 9.2 years ± SD 4.0; 28% were non-ambulatory (gross motor function classification system (GMFCS) level IV-V) and spastic CP was seen in 70%. Comorbidities included Speech impairment 85%, feeding difficulties 86%, and swallowing difficulties 77%, learning difficulties 88%, abnormal behaviour 62%, visual acuity impairment 54%, objective perceptual visual disorders 46%, communication difficulties 45%, epilepsy 35%, hearing impairment 12% and malnutrition 51%. Learning difficulties (OR 10.1, p < 0.001; CI: 3.6-28.1), visual acuity impairment (OR 2.8, p = 0.002; CI: 1.5-5.3), epilepsy (OR 2.3, p = 0.009; CI:1.2-4.3) manual ability classification scale 4-5 (OR 4.7,p = 0.049; CI:1.0-22.2) and CP severity (GMFCS V-VI) OR 6.9 p = 0.002, CI: 2.0-24.0.) were seen as increasing the likelihood of poor school attendance. CONCLUSION: Comorbidities were common, and some were associated with limited school attendance. A multidisciplinary tailored approach to care, with application of available therapeutic interventions for comorbidities is suggested. This may be useful in reducing barriers to school attendance.

Prevalence of fermented foods in the Dutch adult diet and validation of a food frequency questionnaire for estimating their intake in the NQplus cohort.

BACKGROUND: Humans have a long history of consuming fermented foods. However, their prevalence in human diets remains largely undetermined, and there is a lack of validated dietary assessment tools assessing the intake of different fermented products. This study aimed to identify fermented foods consumed in The Netherlands and determine the relative validity of a food frequency questionnaire (FFQ) compared to multiple 24-h recalls for estimating their intake. METHODS: The validation population consisted of 809 participants (53.1 ± 11.9 years) from a Dutch observational cohort (NQplus) who completed a FFQ and multiple 24-h recalls. Fermented foods from the FFQ and recalls were identified and aggregated into conventional food groups. Percent difference in mean intakes, quintile cross-classification, Spearman's correlations, and Bland-Altman analyses were used to evaluate the agreement between the two dietary assessment methods. RESULTS: Approximately 16-18% of foods consumed by this population were fermented, and a further 9-14% were dishes containing a fermented ingredient. Fermented foods with the highest consumption included coffee (~ 453 g/day;~ 0.5% of daily energy intake), yoghurts (~ 88 g/day;~ 2.2%), beer (~ 84 g/day;~ 1.7%), wholegrain bread (~ 81 g/day;~ 9.4%), wine (~ 65 g/day;~ 2.7%), and cheese (~ 32 g/day;~ 5.0%). Mean percent difference between the FFQ and recalls was small for fermented beverages (coffee), breads (brown, white, wholegrain, rye), and fermented dairy (cheeses) (0.3-2.8%), but large for buttermilk and quark (≥53%). All fermented food groups had > 50% of participants classified into the same or adjacent quintile of intake (58%-buttermilk to 89%-fermented beverages). Strong Spearman's correlations (crude/energy-adjusted rs ≥ 0.50) were obtained for fermented beverages (coffee, beer, wine), cereals/grains (wholegrain bread), and dairy (yoghurts). For 'other bread', quark, and buttermilk, correlations were low (rs < 0.20). Bland-Altman analyses revealed good agreement for fermented beverages (coffee, beer), breads (brown, wholegrain, rye, other), pastries, chocolate, and fermented dairy (cheeses) (mean difference: 0.1-9.3). CONCLUSIONS: Fermented food groups with acceptable or good validity across all measures included commonly consumed foods in The Netherlands: fermented beverages (coffee), wholegrain and rye bread, and fermented dairy (cheeses). However, for less frequently consumed foods, such as quark and buttermilk, the levels of agreement were poor and estimates of intake should be interpreted with caution. This report provides the basis for developing a FFQ specific for fermented foods.

Nutrivolatilomics of Urinary and Plasma Samples to Identify Candidate Biomarkers after Cheese, Milk, and Soy-Based Drink Intake in Healthy Humans.

The characterization of volatile compounds in biological fluids offers a distinct approach to study the metabolic imprint of foods on the human metabolome, particularly to identify novel biomarkers of food intake (BFIs) that are not captured by classic metabolomics. Using a combination of dynamic headspace vacuum transfer In Trap extraction and gas chromatography coupled with mass spectrometry, we measured volatile compounds (the "volatilome") in plasma and urine samples from a randomized controlled crossover intervention study in which 11 healthy subjects ingested milk, cheese, or a soy-based drink. More than 2000 volatile compounds were detected in plasma, while 1260 compounds were detected in urine samples. A postprandial response in plasma was confirmed for 697 features. Univariate and multivariate analyses identified four molecules in plasma and 31 molecules in urine samples differentiating the ingestion of the foods, of which three metabolites in plasma and nine in urine were specific to the dairy products. Among these molecules, heptan-2-one, 3,5-dimethyloctan-2-one, and undecan-2-one in plasma and 3-ethylphenol, heptan-2-one, 1-methoxy-2-propyl acetate, and 9-decenoic acid were highly discriminative for dairy or cheese intake. In urine, 22 volatile compounds were highly discriminative for soy-based drink intake. The majority of these molecules have not been reported in humans. Our findings highlight the potential of plasma and urinary volatilomics for detection of novel dietary biomarkers.

Trimethylamine-N-Oxide Postprandial Response in Plasma and Urine Is Lower After Fermented Compared to Non-Fermented Dairy Consumption in Healthy Adults.

Trimethylamine-N-oxide (TMAO) can be produced by the gut microbiota from dietary substrates and is associated with cardiovascular disease. While dairy products contain TMAO precursors, the effect of fermented dairy on TMAO metabolism remains unclear. We used plasma and urine samples collected for two randomised cross-over studies to evaluate the effects of fermented dairy consumption on TMAO metabolism. In Study 1, thirteen healthy young men tested a yogurt and an acidified milk during postprandial tests and a two-week daily intervention. In Study 2, ten healthy adults tested milk and cheese during postprandial tests. TMAO and five related metabolites were measured in plasma and urine by LC-MS/MS and NMR. Faecal microbiota composition was assessed in Study 1 (16S rRNA metagenomics sequencing). Fermented milk products were associated with lower postprandial TMAO responses than non-fermented milks in urine (Study 1, p = 0.01; Study 2, p = 0.02) and in plasma, comparing yogurt and acidified milk (Study 1, p = 0.04). Daily consumption of dairy products did not differentially affect fasting TMAO metabolites. Significant correlations were observed between microbiota taxa and circulating or urinary TMAO concentrations. Fermentation of dairy products appear, at least transiently, to affect associations between dairy products and circulating TMAO levels.

Clinical features and aetiology of cerebral palsy in children from Cross River State, Nigeria.

OBJECTIVE: There are few studies on cerebral palsy (CP) in African children and our study aimed to describe the aetiology, characteristics and severity of CP in children from Nigeria. DESIGN: A population-based study using key informant methodology (KIM) was conducted as part of a clinical research trial. Children aged 4-15 years were clinically assessed for CP. RESULTS: The estimated prevalence of CP using KIM was 2.3/1000 children (95% CI 2.0 to 2.5/1000). 388 children were diagnosed with CP, with Gross Motor Function Classification System level 1 in 70 (18.1%), II in 156 (40.2%), III in 54 (13.9%), IV in 54 (13.9%), V in 54 (13.9%). 300/388 (77.3%) had Manual Ability Classification Scale of level 1-3 and 88 (22.7%) of level 4-5. CP types were spastic in 271 (70%), with 60% of these bilateral and 40% unilateral, ataxic 38 (9.8%), dystonic 18 (4.6%), choreoathetoid 29 (7.5%) and unclassifiable 32 (8.3%). Postneonatal risk factors for CP were seen in 140 (36.1%) children including malaria with seizures 101/140 (72.1%), malaria with coma 21/140 (15.0%), meningitis 12/140 (8.6%), tuberculosis 2/140 (1.4%), sickle cell disease 3/140 (2.2%), HIV 1/221 (0.7%). Prenatal/perinatal risk factors were seen in 248 (63.9%%), birth asphyxia 118 (47.6%) and clinical congenital rubella syndrome 8 (3.3%) and hyperbilirubinaemia 59 (23.8%) were identified as preventable risk factors for CP. CONCLUSION: The profile of CP in this population is similar to that found in other low-income and middle-income countries (LMIC). Some risk factors identified were preventable. Prevention and management strategies for CP designed for LMIC are needed.

The effect of visual support strategies on the quality of life of children with cerebral palsy and cerebral visual impairment/perceptual visual dysfunction in Nigeria: study protocol for a randomized controlled trial.

BACKGROUND: Cerebral visual impairment (CVI), including perceptual visual dysfunction (PVD), is common in children with cerebral palsy (CP). Inventories of questions relating to practical aspects of visual perception in everyday life, in particular the closed-ended Insight Questions Inventory (IQI), can be used to assess CVI/PVD. Studies linking responses to the inventory with specific visual support strategies, aimed at modifying the child's environment and/or behaviour to minimize the impact of the CVI/PVD, have been piloted. The IQI and tailored strategies have not been used in an African population, nor have they been tested in a controlled trial. This trial will compare the effectiveness of the IQI and linked visual support strategies versus general supportive treatments on the quality of life of children with CVI/PVD and CP through a randomized controlled trial. METHODS/DESIGN: This is a prospective, double-blind, parallel-arm, randomized controlled trial. The primary outcome is change in quality of life scores between the two arms of the trial at 6 weeks, assessed using the Paediatric Quality of Life Inventory (PedsQL) generic 4.0 and CP 3.0 module. All children will undergo baseline assessment including the Open Questions Inventory, IQI, PedsQL 3.0, PedsQL 4.0 generic, and the Strengths and Difficulties Questionnaire (SDQ). Eligible children with CP aged 4 years to < 16 years will be stratified and blocked by the age groups 4-9 and 10 to < 16 years and by Gross Motor Function Classification System (GMFCS) levels 1-3 and 4-5. Families in the intervention arm will receive tailored insight visual support strategies and telephone calls during the 6-week trial period. The control arm will receive standard treatment and the intervention after the 6-week trial period. Follow-up interviews will be performed in both arms at 6 weeks with a repeat administration of the PedsQL CP 4.0 and 3.0, the IQI and the SDQ. Secondary outcomes include a change in functional vision. DISCUSSION: This randomized controlled trial will provide evidence of the effectiveness of this intervention for children with CP in a resource-poor setting. TRIAL REGISTRATION: Pan African Clinical Trials Registration, PACTR201612001886396 . Registered on 3 December 2016.

Assessment of lactase activity in humans by measurement of galactitol and galactonate in serum and urine after milk intake.

Background: Lactase is an enzyme that hydrolyzes lactose into glucose and galactose in the small intestine, where they are absorbed. Hypolactasia is a common condition, primarily caused by genetic programming, that leads to lactose maldigestion and, in certain cases, lactose intolerance. Galactitol and galactonate are 2 products of hepatic galactose metabolism that are candidate markers for the intake of lactose-containing foods. Objectives: The primary objective of the study was to explore the changes in serum and urine metabolomes during postprandial dairy product tests through the association between lactase persistence genotype and the postprandial dynamics of lactose-derived metabolites. Methods: We characterized the 6-h postprandial serum kinetics and urinary excretion of lactose, galactose, galactitol, and galactonate in 14 healthy men who had consumed a single dose of acidified milk (800 g) which contained 38.8 g lactose. Genotyping of LCT-13910 C/T (rs4988235) was performed to assess primary lactase persistence. Results: There were 2 distinct postprandial responses, classified as high and low metabolite responses, observed for galactose, and its metabolites galactitol and galactonate, in serum and urine. In all but 1 subject, there was a concordance between the high metabolite responses and genetic lactase persistence and between the low metabolite responses and genetic lactase nonpersistence (accuracy 0.92), galactitol and galactonate being more discriminative than galactose. Conclusions: Postprandial galactitol and galactonate after lactose overload appear to be good proxies for genetically determined lactase activity. The development of a noninvasive lactose digestion test based on the measurement of these metabolites in urine could be clinically useful. This trial was registered at clinicaltrials.gov as NCT02230345.

Metabolic Footprinting of Fermented Milk Consumption in Serum of Healthy Men.

Background: Fermentation is a widely used method of natural food preservation that has consequences on the nutritional value of the transformed food. Fermented dairy products are increasingly investigated in view of their ability to exert health benefits beyond their nutritional qualities. Objective: To explore the mechanisms underpinning the health benefits of fermented dairy intake, the present study followed the effects of milk fermentation, from changes in the product metabolome to consequences on the human serum metabolome after its ingestion. Methods: A randomized crossover study design was conducted in 14 healthy men [mean age: 24.6 y; mean body mass index (in kg/m2): 21.8]. At the beginning of each test phase, serum samples were taken 6 h postprandially after the ingestion of 800 g of a nonfermented milk or a probiotic yogurt. During the 2-wk test phases, subjects consumed 400 g of the assigned test product daily (200 g, 2 times/d). Serum samples were taken from fasting participants at the end of each test phase. The serum metabolome was assessed through the use of LC-MS-based untargeted metabolomics. Results: Postprandial serum metabolomes after milk or yogurt intake could be differentiated [orthogonal projections to latent structures discriminant analysis (OPLS-DA) Q2 = 0.74]. Yogurt intake was characterized by higher concentrations of 7 free amino acids (including proline, P = 0.03), reduced concentrations of 5 bile acids (including glycocholic acid, P = 0.04), and modulation of 4 indole derivative compounds (including indole lactic acid, P = 0.01). Fasting serum samples after 2 wk of daily intake of milk or yogurt could also be differentiated based on their metabolic profiles (OPLS-DA Q2 = 0.56) and were discussed in light of the postprandial results. Conclusion: Metabolic pathways related to amino acids, indole derivatives, and bile acids were modulated in healthy men by the intake of yogurt. Further investigation to explore novel health effects of fermented dairy products is warranted.This trial was registered at clinicaltrials.gov as NCT02230345.

Modulation of the peripheral blood transcriptome by the ingestion of probiotic yoghurt and acidified milk in healthy, young men.

The metabolic health benefits of fermented milks have already been investigated using clinical biomarkers but the development of transcriptomic analytics in blood offers an alternative approach that may help to sensitively characterise such effects. We aimed to assess the effects of probiotic yoghurt intake, compared to non-fermented, acidified milk intake, on clinical biomarkers and gene expression in peripheral blood. To this end, a randomised, crossover study was conducted in fourteen healthy, young men to test the two dairy products. For a subset of seven subjects, RNA sequencing was used to measure gene expression in blood collected during postprandial tests and after two weeks daily intake. We found that the postprandial response in insulin was different for probiotic yoghurt as compared to that of acidified milk. Moreover changes in several clinical biomarkers were associated with changes in the expression of genes representing six metabolic genesets. Assessment of the postprandial effects of each dairy product on gene expression by geneset enrichment analysis revealed significant, similar modulation of inflammatory and glycolytic genes after both probiotic yoghurt and acidified milk intake, although distinct kinetic characteristics of the modulation differentiated the dairy products. The aryl hydrocarbon receptor was a major contributor to the down-regulation of the inflammatory genesets and was also positively associated with changes in circulating insulin at 2h after yoghurt intake (p = 0.05). Daily intake of the dairy products showed little effect on the fasting blood transcriptome. Probiotic yoghurt and acidified milk appear to affect similar gene pathways during the postprandial phase but differences in the timing and the extent of this modulation may lead to different physiological consequences. The functional relevance of these differences in gene expression is supported by their associations with circulating biomarkers.

Stigma and functional disability in relation to marriage and employment in young people with epilepsy in rural Tanzania.

PURPOSE: To assess the impact of childhood epilepsy on social transitioning outcomes for young people with epilepsy (YPWE) living in Tanzania, and to explore influences on these outcomes. METHODS: At six years from baseline, we followed up 84 YPWE and 79 age- sex- and village- matched controls recruited into a case-control study of childhood epilepsy in rural northern Tanzania. Data were collected from interviews with young people and their carers using a structured questionnaire. Perceived stigma was evaluated using the Kilifi Stigma Score and functional disability using the Barthel Index (BI). The effects of age, gender, functional disability and stigma on selected markers of social transitioning (education, employment and relationships) were estimated using multivariable modelling. RESULTS: Fewer YPWE than controls were in an intimate relationship (42.3% vs. 76.9%) or in education or paid employment (33.3% vs. 91.1%) and they reported elevated perceived stigma scores (27.4% vs. 3.8%). Among YPWE, a positive education or employment outcome was predicted by a lower seizure frequency (adjusted OR 3.79) and a higher BI score (adj. OR 12.12); a positive relationship outcome was predicted by a higher BI score (adj. OR 45.86) and being male (adj. OR 8.55). CONCLUSION: YPWE were more likely to experience adverse employment, educational and relationship outcomes in the transition to adult life than controls, with the greatest disadvantage experienced by females, those with greater functional disability and those with poorer seizure control. Markers of social transitioning should be included in any prospective evaluation of interventions designed to support these groups.

Blood lactose after dairy product intake in healthy men.

The absence of a dedicated transport for disaccharides in the intestine implicates that the metabolic use of dietary lactose relies on its prior hydrolysis at the intestinal brush border. Consequently, lactose in blood or urine has mostly been associated with specific cases in which the gastrointestinal barrier is damaged. On the other hand, lactose appears in the blood of lactating women and has been detected in the blood and urine of healthy men, indicating that the presence of lactose in the circulation of healthy subjects is not incompatible with normal physiology. In this cross-over study we have characterised the postprandial kinetics of lactose, and its major constituent, galactose, in the serum of fourteen healthy men who consumed a unique dose of 800 g milk or yogurt. Genetic testing for lactase persistence and microbiota profiling of the subjects were also performed. Data revealed that lactose does appear in serum after dairy intake, although with delayed kinetics compared with galactose. Median serum concentrations of approximately 0·02 mmol/l lactose and approximately 0·2 mmol/l galactose were observed after the ingestion of milk and yogurt respectively. The serum concentrations of lactose were inversely correlated with the concentrations of galactose, and the variability observed between the subjects' responses could not be explained by the presence of the lactase persistence allele. Finally, lactose levels have been associated with the abundance of the Veillonella genus in faecal microbiota. The measurement of systemic lactose following dietary intake could provide information about lactose metabolism and nutrient transport processes under normal or pathological conditions.

Identification of Urinary Food Intake Biomarkers for Milk, Cheese, and Soy-Based Drink by Untargeted GC-MS and NMR in Healthy Humans.

The measurement of food intake biomarkers (FIBs) in biofluids represents an objective tool for dietary assessment. FIBs of milk and cheese still need more investigation due to the absence of candidate markers. Thus, an acute intervention study has been performed to sensitively and specifically identify candidate FIBs. Eleven healthy male and female volunteers participated in the randomized, controlled crossover study that tested a single intake of milk and cheese as test products, and soy-based drink as a control. Urine samples were collected at baseline and up to 24 h at distinct time intervals (0-1, 1-2, 2-4, 4-6, 6-12, and 12-24 h) and were analyzed using an untargeted multiplatform approach (GC-MS and 1H NMR). Lactose, galactose, and galactonate were identified exclusively after milk intake while for other metabolites (allantoin, hippurate, galactitol, and galactono-1,5-lactone) a significant increase has been observed. Urinary 3-phenyllactic acid was the only compound specifically reflecting cheese intake although alanine, proline, and pyroglutamic acid were found at significantly higher levels after cheese consumption. In addition, several novel candidate markers for soy drink were identified, such as pinitol and trigonelline. Together, these candidate FIBs of dairy intake could serve as a basis for future validation studies under free-living conditions.

Probiotic yogurt and acidified milk similarly reduce postprandial inflammation and both alter the gut microbiota of healthy, young men.

Probiotic yogurt and milk supplemented with probiotics have been investigated for their role in 'low-grade' inflammation but evidence for their efficacy is inconclusive. This study explores the impact of probiotic yogurt on metabolic and inflammatory biomarkers, with a parallel study of gut microbiota dynamics. The randomised cross-over study was conducted in fourteen healthy, young men to test probiotic yogurt compared with milk acidified with 2 % d-(+)-glucono-δ-lactone during a 2-week intervention (400 g/d). Fasting assessments, a high-fat meal test (HFM) and microbiota analyses were used to assess the intervention effects. Baseline assessments for the HFM were carried out after a run-in during which normal milk was provided. No significant differences in the inflammatory response to the HFM were observed after probiotic yogurt compared with acidified milk intake; however, both products were associated with significant reductions in the inflammatory response to the HFM compared with the baseline tests (assessed by IL6, TNFα and chemokine ligand 5) (P<0·001). These observations were accompanied by significant changes in microbiota taxa, including decreased abundance of Bilophila wadsworthia after acidified milk (log 2-fold-change (FC)=-1·5, P adj=0·05) and probiotic yogurt intake (FC=-1·3, P adj=0·03), increased abundance of Bifidobacterium species after acidified milk intake (FC=1·4, P adj=0·04) and detection of Lactobacillus delbrueckii spp. bulgaricus (FC=7·0, P adj<0·01) and Streptococcus salivarius spp. thermophilus (FC=6·0, P adj<0·01) after probiotic yogurt intake. Probiotic yogurt and acidified milk similarly reduce postprandial inflammation that is associated with a HFM while inducing distinct changes in the gut microbiota of healthy men. These observations could be relevant for dietary treatments that target 'low-grade' inflammation.

Decreasing Insulin Sensitivity in Women Induces Alterations in LH Pulsatility.

CONTEXT: Obesity is associated with neuroendocrine reproductive alterations and decreased fertility. OBJECTIVE: The objective of the study was to gain insight into the neuroendocrine mechanisms implicated in these alterations. DESIGN: The effects on pulsatile LH secretion of 28 days of a hypercaloric diet were studied in lean and regularly cycling female volunteers. Approximately 50% extra calories (3 g sucrose/kg body weight per day and 1 g fat/kg body weight per day) were added to their individual daily requirements. Spontaneous and insulin-stimulated LH secretion was recorded on 2 different days, before and at the end of the caloric load. RESULTS: The hypercaloric diet induced an average weight gain of 2.0 ± 0.3 kg (P < .05), corresponding to a body mass index increase of 0.7 ± 0.1 kg/m(2) (P < .05). A concomitant decrease of 11.6% ± 4.6% in whole-body insulin sensitivity was also observed (δ = -1.6 ± 0.7 mg/kg · min glucose; P < .05). The frequency of spontaneous and insulin-stimulated pulsatile LH secretion was increased by 17.9% ± 9.0% and 26.5% ± 9.0%, respectively (both P < .05). Spontaneous LH peak amplitude was decreased by 26.5% ± 9.0% (δ = -0.7 ± 0.36 U/L; P < .05), a change correlated with insulin sensitivity. CONCLUSIONS: Short-term weight gain in normal female volunteers induces alterations of LH secretion reminiscent to those observed in obesity. A decrease in insulin sensitivity may constitute a mechanistic link between obesity and its associated neuroendocrine dysfunctions.

Cognition and behavior in a prevalent cohort of children with epilepsy in rural northern Tanzania: A three-year follow-up study.

OBJECTIVES: Eighty-five percent of the 33 million children with epilepsy (CWE) worldwide live in low- and middle-income countries (LMICs). There is limited research into epilepsy-related comorbidities in LMICs, and there are no studies of the long-term progression of behavioral and intellectual difficulties in childhood epilepsy in sub-Saharan Africa. We aimed to assess behavior and cognition at three-year follow-up in CWE in rural Tanzania. METHODS: In 2010, a cross-sectional study identified 112 CWE 6 to 14years of age and 113 age- and sex-matched controls in the Hai district of northern Tanzania. From March to June 2013, cases and controls (now 10 to 18years of age) were followed up. At baseline, behavior was assessed using the Rutter A Questionnaire and cognition using the Goodenough-Harris Drawing Test. Details of current seizure frequency and antiepileptic drug (AED) use among CWE were collected. RESULTS: At follow-up, cases had significantly more behavioral difficulties compared with controls (48% of 108 cases versus 14% of 103 controls (p<0.001)). Additionally, 69% of the cases and 16% of the controls had cognitive impairment (p<0.001). In CWE with decreased seizure frequency from baseline to follow-up, behavior had improved significantly. At follow-up, there was no significant difference in behavior between CWE with decreased seizure frequency and those with good seizure control throughout. SIGNIFICANCE: Behavioral difficulties and cognitive impairment are common among CWE in this population. Improved access to AED treatment and subsequent improved seizure control may reduce the frequency of behavioral difficulties seen in this population.

Cysticercosis and epilepsy in rural Tanzania: a community-based case-control and imaging study.

OBJECTIVE: To assess the contribution of neurocysticercosis (NCC) to the burden of epilepsy in a rural Tanzanian population. METHODS: We identified adult people with epilepsy (PWE) in a door-to-door study in an established demographic surveillance site. PWE and community controls were tested for antibodies to Taenia solium, the causative agent of NCC, and all PWE were offered a computed tomography (CT) head scan. Data on household occupancy and sanitation, pig-keeping and pork consumption were collected from PWE and controls and associations with epilepsy were assessed using chi-square or Fisher's exact tests. RESULTS: Six of 218 PWE had antibodies to T. solium (2.8%; 95% CI 0.6-4.9), compared to none of 174 controls (Fisher's exact test, P = 0.04). Lesions compatible with NCC were seen in eight of 200 CT scans (4.0%; 95% CI 1.3-6.7). A total of 176 PWE had both investigations of whom two had positive serology along with NCC-compatible lesions on CT (1.1%; 95% 0.3-4.0). No associations between epilepsy and any risk factors for NCC were identified. CONCLUSIONS: Neurocysticercosis is present in this population but at a lower prevalence than elsewhere in Tanzania and sub-Saharan Africa. Insights from low-prevalence areas may inform public health interventions designed to reduce the burden of preventable epilepsy.

Growth parameters and childhood epilepsy in Hai District, Tanzania: a community-based study.

AIM: This cross-sectional study examined whether growth parameters were associated with epilepsy in children living in a rural community in sub-Saharan Africa (SSA). MATERIALS AND METHODS: A cross-sectional study was performed in the Hai District Demographic Surveillance Site (HDSS), Tanzania in which 6-14 year old children with epilepsy (CWE) were identified. Age matched controls were randomly selected from the Hai census database for comparison. Anthropometric measurements were used to assess the nutritional status of the children and body mass index (BMI) calculated. Associations between social, demographic and nutritional factors and epilepsy were assessed using multivariable logistic regression. RESULTS: 112 CWE were identified and were compared with 113 controls. There was no significant difference in the BMI between cases and controls (T-test, p-value of 0.117). Amongst cases, there were no significant associations between BMI and motor difficulties, antiepileptic drug use, cognitive or behavioural problems, early-onset epilepsy or seizure frequency. In the whole group, BMI was significantly associated with socio-economic status (p=0.037) and age. DISCUSSION: There was no significant difference found between CWE and matched controls with respect to nutritional status. This suggests that there is no causal association between under nutrition and epilepsy in this community. Nutritional assessment is still important as part of the comprehensive care of CWE.