Background Diet-induced obesity (DIO) is a significant health concern which has been linked to structural and functional changes in the gut microbiota. Exercise (Ex) is effective in preventing ...obesity, but whether Ex alters the gut microbiota during development with high fat (HF) feeding is unknown. Objective Determine the effects of voluntary Ex on the gastrointestinal microbiota in LF-fed mice and in HF-DIO. Methods Male C57BL/6 littermates (5 weeks) were distributed equally into 4 groups: low fat (LF) sedentary (Sed) LF/Sed, LF/Ex, HF/Sed and HF/Ex. Mice were individually housed and LF/Ex and HF/Ex cages were equipped with a wheel and odometer to record Ex. Fecal samples were collected at baseline, 6 weeks and 12 weeks and used for bacterial DNA isolation. DNA was subjected both to quantitative PCR using primers specific to the 16S rRNA encoding genes for Bacteroidetes and Firmicutes and to sequencing for lower taxonomic identification using the Illumina MiSeq platform. Data were analyzed using a one or two-way ANOVA or Pearson correlation. Results HF diet resulted in significantly greater body weight and adiposity as well as decreased glucose tolerance that were prevented by voluntary Ex (p<0.05). Visualization of Unifrac distance data with principal coordinates analysis indicated clustering by both diet and Ex at week 12. Sequencing demonstrated Ex-induced changes in the percentage of major bacterial phyla at 12 weeks. A correlation between total Ex distance and the Delta Ct Bacteroidetes: Delta Ct Firmicutes ratio from qPCR demonstrated a significant inverse correlation (r2 = 0.35, p = 0.043). Conclusion Ex induces a unique shift in the gut microbiota that is different from dietary effects. Microbiota changes may play a role in Ex prevention of HF-DIO.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Environmental enteric dysfunction (EED) may be an important modifiable cause of child stunting. We described the evolution of EED biomarkers from birth to 18 months in rural Zimbabwe and tested the ...independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF), on EED.
The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial was a 2x2 factorial cluster-randomised trial of improved IYCF and improved WASH on child stunting and anaemia at 18 months of age. 1169 infants born to HIV-negative mothers provided plasma and faecal specimens at 1, 3, 6, 12, and 18 months of age. We measured EED biomarkers that reflect all domains of the hypothesized pathological pathway. Markers of intestinal permeability and intestinal inflammation declined over time, while markers of microbial translocation and systemic inflammation increased between 1-18 months. Markers of intestinal damage (I-FABP) and repair (REG-1β) mirrored each other, and citrulline (a marker of intestinal epithelial mass) increased from 6 months of age, suggesting dynamic epithelial turnover and regeneration in response to enteric insults. We observed few effects of IYCF and WASH on EED after adjustment for multiple comparisons. The WASH intervention decreased plasma IGF-1 at 3 months (β:0.89, 95%CI:0.81,0.98) and plasma kynurenine at 12 months (β: 0.92, 95%CI:0.87,0.97), and increased plasma IGF-1 at 18 months (β:1.15, 95%CI:1.05,1.25), but these small WASH effects did not translate into improved growth.
Overall, we observed dynamic trends in EED but few effects of IYCF or WASH on biomarkers during the first 18 months after birth, suggesting that these interventions did not impact EED. Transformative WASH interventions are required to prevent or ameliorate EED in low-income settings.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Since ancient times, people have taken advantage of the antimicrobial effects of colloidal silver particles. Aside from the medical prospects, silver nanoparticles are found in a wide range of ...commercially available consumer products ranging from cosmetics to household cleansers. Current synthetic methods for creating silver nanoparticles typically call for potentially hazardous chemicals, extreme heat, and produce environmentally dangerous byproducts. Therefore, it is essential that novel "green" synthesis of nanoparticles becomes a reality, and it is imperative to fully analyze the potential toxic effects of these nanoparticles. In this study, we have shown that by reducing silver nitrate in solutions of tea extract or epicatechin of varying concentrations, spherical silver nanoparticles were formed that had controllable size distributions depending on the concentration of tea extract or epicatechin in the samples. Our ultra-resolution microscopy demonstrated that the nanoparticles were in fact interacting with the keratinocytes. Furthermore, evaluation of mitochondrial function (MTS) to assess cell viability and membrane integrity (LDH) in human keratinocytes showed that the silver nanoparticles were nontoxic. These results demonstrated that these nanoparicles are potentially biocompatible and warrant further evaluation in other biological systems.
A "green" synthetic protocol is described for the synthesis of silver nanoparticles using tea polyphenols, and the resulting nanoparticles were found to be nontoxic in mitochondrial function (MTS) and membrane integrity (LDH) in alveolar rat macrophages and human keratinocyte cells, respectively.
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IJS, KILJ, NUK, UL, UM, UPUK
Background and Objectives
Neoadjuvant chemoradiation and liver transplantation may be offered for unresectable perihilar cholangiocarcinoma (pCCA). This study aimed to determine the dropout rate and ...survival of patients who entered a national tri‐modality protocol.
Method
Patients enrolled Jan 2009‐Aug 2015 were included. Enrolment criteria: ≤65 years, brush biopsy‐proven unresectable pCCA <3.5 cm diameter. Conformal radiotherapy was given concurrently with Capecitabine. Following surgical staging, patients received maintenance Cisplatin and Gemcitabine until transplant or progression. Time to event analyses were performed from start of neoadjuvant therapy.
Results
Of 43 patients screened, 18 started treatment; median age 53.9 (26.7‐62.8) years, tumour diameter 2.7 (2.0‐3.4) cm. 11/18 dropped out due to metastatic disease identified during chemoradiation (n = 2), surgical staging (n = 6), or maintenance chemotherapy (n = 3). Six patients underwent transplantation. Median follow up was 17.6 (4.9‐57.7) months and overall survival 16.4 months. One and two year survival was 70.6% and 35.3%, respectively. One and 2 year post transplant survival was 83.3% and 55.6%. Median progression free survival was 11.5 months.
Conclusion
Neoadjuvant chemoradiation and liver transplantation for unresectable early stage pCCA is feasible, although with high rates of dropout and disease progression. Further research is required to determine factors to help select patients for treatment.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Poverty and human capital development are inextricably linked and therefore research on human capital typically incorporates measures of economic well-being. In the context of randomized trials of ...health interventions, for example, such measures are used to: 1) assess baseline balance; 2) estimate covariate-adjusted analyses; and 3) conduct subgroup analyses. Many factors characterize economic well-being, however, and analysts often generate summary measures such as indices of household socio-economic status or wealth. In this paper, a household wealth index is developed and tested for participants in the cluster-randomized Sanitation, Hygiene, Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe.
Building on the approach used in the Zimbabwe Demographic and Health Survey (ZDHS), we combined a set of housing characteristics, ownership of assets and agricultural resources into a wealth index using principal component analysis (PCA) on binary variables. The index was assessed for internal and external validity. Its sensitivity was examined considering an expanded set of variables and an alternative statistical approach of polychoric PCA. Correlation between indices was determined using the Spearman's rank correlation coefficient and agreement between quintiles using a linear weighted Kappa statistic. Using the 2015 ZDHS data, we constructed a separate index and applied the loadings resulting from that analysis to the SHINE study population, to compare the wealth distribution in the SHINE study with rural Zimbabwe.
The derived indices using the different methods were highly correlated (r>0.9), and the wealth quintiles derived from the different indices had substantial to near perfect agreement (linear weighted Kappa>0.7). The indices were strongly associated with a range of assets and other wealth measures, indicating both internal and external validity. Households in SHINE were modestly wealthier than the overall population of households in rural Zimbabwe.
The SHINE wealth index developed here is a valid and robust measure of wealth in the sample.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in children. We aimed to assess the safety and efficacy of an anti-RSV monoclonal ...antibody (motavizumab) in healthy term (≥36 weeks' gestational age) infants for the prevention of medically attended RSV acute lower respiratory tract infections. Methods This phase 3, double-blind, placebo-controlled, randomised trial enrolled healthy Native American infants aged 6 months or younger who were born at 36 weeks' gestational age in southwestern USA, on the Navajo Nation, the White Mountain Apache reservation, and the San Carlos Apache Indian reservation. Participants were randomly assigned (2:1) to receive either five monthly intramuscular doses of motavizumab (15 mg/kg) or placebo. They were followed up for 150 days after the first dose, and the primary endpoints were respiratory admission to hospital with a positive result for RSV by RT-PCR and death caused by RSV. Participants were followed up for medically attended wheezing until they reached age 3 years. Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov , number NCT00121108. Findings During the autumn seasons (October to December) between 2004 and 2007, 2127 infants of the 2596 infants enrolled were randomly assigned to receive either motavizumab (1417) or placebo (710). After ITT analysis, motavizumab resulted in an 87% relative reduction (relative risk RR 0·13, 95% CI 0·08–0·21) in the proportion of infants admitted to hospital with RSV (21 2% of 1417 participants who received motavizumab; 80 11% of 710 participants who received placebo, p<0·0001). Serious adverse events were less common in particpants taking motavizumab (212 15%) than particpants on placebo (148 21%). Six deaths occurred in study participants (motavizumab, n=4 0·3%; placebo, n=2 0·3%); none were deemed to be related to the study product. Hypersensitivity events were more common in patients given motavizumab (208 14·7%) than in placebo recipients (87 12·3%; p=0·14). There was no effect on rates of medically attended wheezing in children aged 1–3 years (190 14·9% of participants randomly assigned to receive motavizumab vs 90 14·0% participants randomly assigned to receive placebo). Interpretation To our knowledge, this is the only trial of an anti-RSV antibody to prevent serious RSV disease in healthy term infants. Motavizumab significantly reduced the RSV-associated inpatient and outpatient burden and set a benchmark for the efficacy of RSV prevention strategies. The findings do not support a direct, generalisable, causal association between RSV lower respiratory tract infection and subsequent long-term wheezing in term infants. Funding MedImmune.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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