Brief Education to Promote Maternal Influenza Vaccine Uptake: A Randomized Controlled Trial

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Global Regulation on microRNA in Hepatitis B Virus-Associated Hepatocellular Carcinoma

Recent work has revealed the causative links between deregulation of microRNAs (miRNAs) and cancer development. In hepatocellular carcinoma (HCC), aberrant expression of miRNAs has been observed, but the molecular mechanisms that contribute to such changes remains to be elucidated. Here, we reported the analysis of miRNA expression in 94 pairs of tumor and adjacent nontumor tissues from HBV-associated HCC in Chinese patients. We found miRNAs were aberrantly expressed in HCC tissues. To investigate the cause of such deregulation, we detected changes in DNA copy number by measuring locus-specific hybridization intensity, and found changes in expression of several miRNAs are correlated with genomic amplification or deletion. For example, the genomic regions of miR-30d and miR-151 were amplified in ∼50% of HCC tumor tissues, and the expressions of these miRNAs are significantly correlated with DNA copy number. We also employed cDNA microarray data, and provide evidence that key regulators of the miRNA biosynthetic pathway, including DROSHA, DGCR8, AGO1, and AGO2, are frequently overexpressed in HCC. This study provides molecular clues that may contribute to the global changes of miRNA expression in HCC. Copyright © 2011, Mary Ann Liebert, Inc.published_or_final_versio

Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration

Microglia are the resident innate immune cells in the brain with a major role in orchestrating immune responses. They also provide a frontline of host defense in the central nervous system (CNS) through their active phagocytic capability. Being a professional phagocyte, microglia participate in phagocytic and autophagic clearance of cellular waste and debris as well as toxic protein aggregates, which relies on optimal lysosomal acidification and function. Defective microglial lysosomal acidification leads to impaired phagocytic and autophagic functions which result in the perpetuation of neuroinflammation and progression of neurodegeneration. Reacidification of impaired lysosomes in microglia has been shown to reverse neurodegenerative pathology in Alzheimer's disease. In this review, we summarize key factors and mechanisms contributing to lysosomal acidification impairment and the associated phagocytic and autophagic dysfunction in microglia, and how these defects contribute to neuroinflammation and neurodegeneration. We further discuss techniques to monitor lysosomal pH and therapeutic agents that can reacidify impaired lysosomes in microglia under disease conditions. Finally, we propose future directions to investigate the role of microglial lysosomal acidification in lysosome-mitochondria crosstalk and in neuron-glia interaction for more comprehensive understanding of its broader CNS physiological and pathological implications

Effect on Baby-Friendly Hospital Steps When Hospitals Implement a Policy to Pay for Infant Formula

Background: The Baby-Friendly Hospital Initiative requires hospitals to pay market price for infant formula. No studies have specifically examined the effect of hospitals paying for infant formula on breastfeeding mothers' exposure to Baby-Friendly steps. Objectives: To investigate the effect of hospitals implementing a policy of paying for infant formula on new mothers' exposure to Baby-Friendly steps and examine the effect of exposure to Baby-Friendly steps on breastfeeding rates. Methods: We used a repeated prospective cohort study design. We recruited 2 cohorts of breastfeeding mother-infant pairs (n = 2470) in the immediate postnatal period from 4 Hong Kong public hospitals and followed them by telephone up to 12 months postpartum. We assessed participants' exposure to 6 Baby-Friendly steps by extracting data from the medical record and by maternal self-report. Results: After hospitals began paying for infant formula, new mothers were more likely to experience 4 out of 6 Baby-Friendly steps. Breastfeeding initiation within the first hour increased from 28.7% to 45%, and in-hospital exclusive breastfeeding rates increased from 17.9% to 41.4%. The proportion of mothers who experienced all 6 Baby-Friendly steps increased from 4.8% to 20.5%. The risk of weaning was progressively higher among participants experiencing fewer Baby-Friendly steps. Each additional step experienced by new mothers decreased the risk of breastfeeding cessation by 8% (hazard ratio = 0.92; 95% CI, 0.89-0.95). Conclusion: After implementing a policy of paying for infant formula, breastfeeding mothers were exposed to more Baby-Friendly steps, and exposure to more steps was significantly associated with a lower risk of breastfeeding cessation.postprin

Nanoscale dynamics of peptidoglycan assembly during the cell cycle of Streptococcus pneumoniae.

Dynamics of cell elongation and septation are key determinants of bacterial morphogenesis. These processes are intimately linked to peptidoglycan synthesis performed by macromolecular complexes called the elongasome and the divisome. In rod-shaped bacteria, cell elongation and septation, which are dissociated in time and space, have been well described. By contrast, in ovoid-shaped bacteria, the dynamics and relationships between these processes remain poorly understood because they are concomitant and confined to a nanometer-scale annular region at midcell. Here, we set up a metabolic peptidoglycan labeling approach using click chemistry to image peptidoglycan synthesis by single-molecule localization microscopy in the ovoid bacterium Streptococcus pneumoniae. Our nanoscale-resolution data reveal spatiotemporal features of peptidoglycan assembly and fate along the cell cycle and provide geometrical parameters that we used to construct a morphogenesis model of the ovoid cell. These analyses show that septal and peripheral peptidoglycan syntheses first occur within a single annular region that later separates in two concentric regions and that elongation persists after septation is completed. In addition, our data reveal that freshly synthesized peptidoglycan is remodeled all along the cell cycle. Altogether, our work provides evidence that septal peptidoglycan is synthesized from the beginning of the cell cycle and is constantly remodeled through cleavage and insertion of material at its periphery. The ovoid-cell morphogenesis would thus rely on the relative dynamics between peptidoglycan synthesis and cleavage rather than on the existence of two distinct successive phases of peripheral and septal synthesis

Effect of a hospital policy of not accepting free infant formula on in-hospital formula supplementation rates and breast-feeding duration

OBJECTIVE: To investigate the effect of public hospitals in Hong Kong not accepting free infant formula from manufacturers on in-hospital formula supplementation rates and breast-feeding duration. DESIGN: Prospective cohort study. SETTING: In-patient postnatal units of four public hospitals in Hong Kong. SUBJECTS: Two cohorts of breast-feeding mother-infant pairs (n 2560). Cohort 1 (n 1320) was recruited before implementation of the policy to stop accepting free infant formula and cohort 2 (n 1240) was recruited after policy implementation. Participants were followed prospectively for 12 months or until they stopped breast-feeding. RESULTS: The mean number of formula supplements given to infants in the first 24 h was 2·70 (sd 3·11) in cohort 1 and 1·17 (sd 1·94) in cohort 2 (P<0·001). The proportion of infants who were exclusively breast-fed during the hospital stay increased from 17·7 % in cohort 1 to 41·3 % in cohort 2 (P<0·001) and the risk of breast-feeding cessation was significantly lower in cohort 2 (hazard ratio=0·81; 95 % CI 0·73, 0·90). Participants who non-exclusively breast-fed during the hospital stay had a significantly higher risk of stopping any or exclusive breast-feeding. Higher levels of formula supplementation also increased the risk of breast-feeding cessation in a dose-response pattern. CONCLUSIONS: After implementation of a hospital policy to pay market price for infant formula, rates of in-hospital formula supplementation were reduced and the rates of in-hospital exclusive breast-feeding and breast-feeding duration increased.postprin

Regional variation in primary care improvement strategies and policy: case studies that consider qualitative contextual data for performance measurement in three Canadian provinces

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordOBJECTIVE: To explore regional primary care improvement strategies that are potentially determinants of primary care performance. DESIGN: Multiple comparative embedded case study. SETTING: Three regions in Canada: Fraser East, British Columbia; Eastern Ontario Health Unit, Ontario; Central Zone, Nova Scotia. DATA SOURCES: (1) In-depth interviews with purposively selected key informants (eg, primary care decision-makers, physician leads, regulatory agencies) and focus groups with patients and clinicians (n=68 participants) and (2) published and grey literature (n=205 documents). OUTCOME MEASURES: Variations in spread and uptake of primary care improvement strategies across the three study regions. NVivo (V.11) was used to manage data and perform content analysis to identify categories within and across cases. The coding structure was developed by researchers through iterative collaboration, using inductive and deductive processes. RESULTS: Six overarching primary care improvement strategies, differing in focus and spread, were implemented across the three study regions: interprofessional team-based approaches, provider skill mix expansion, physician groups and networks, information systems, remuneration and performance measurement and reporting infrastructure. CONCLUSION: The addition of information on regional improvement strategies to primary care performance reports could add important contextual insights into primary care performance results. This could help identify possible drivers of reported performance outcomes and levers for change in practice, regional and system-level settings.Canadian Institutes of Health ResearchMichael Smith Foundation for Health Researc

Prediction of photoperiodic regulators from quantitative gene circuit models

Photoperiod sensors allow physiological adaptation to the changing seasons. The external coincidence hypothesis postulates that a light-responsive regulator is modulated by a circadian rhythm. Sufficient data are available to test this quantitatively in plants, though not yet in animals. In Arabidopsis, the clock-regulated genes CONSTANS (CO) and FLAVIN, KELCH, F-BOX (FKF1) and their lightsensitive proteins are thought to form an external coincidence sensor. We use 40 timeseries of molecular data to model the integration of light and timing information by CO, its target gene FLOWERING LOCUS T (FT), and the circadian clock. Among other predictions, the models show that FKF1 activates FT. We demonstrate experimentally that this effect is independent of the known activation of CO by FKF1, thus we locate a major, novel controller of photoperiodism. External coincidence is part of a complex photoperiod sensor: modelling makes this complexity explicit and may thus contribute to crop improvement

Heritage branding orientation: The case of Ach. Brito and the dynamics between corporate and product heritage brands

The notion of heritage branding orientation is introduced and explicated. Heritage branding orientation is designated as embracing both product and corporate brands and differs from corporate heritage brand orientation which has an explicit corporate focus. Empirical insights are drawn from an in-depth and longitudinal case study of Ach. Brito, a celebrated Portuguese manufacturer of soaps and toiletries. This study shows how, by the pursuance of a strategy derived from a heritage branding orientation Ach. Brito – after a prolonged period of decline – achieved a dramatic strategic turnaround. The findings reveal how institutional heritage can be a strategic resource via its adoption and activation at both the product and corporate levels. Moreover, the study showed how the bi-lateral interplay between product and corporate brand levels can be mutually reinforcing. In instrumental terms, the study shows how heritage can be activated and articulated in different ways. For instance, it can re-position both product and/or corporate brands; it can be meaningfully informed by product brand heritage and shape corporate heritage; and can be of strategic importance to both medium-sized and small enterprises