Infectious Diseases - Research Publications
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ItemPI3K Activation in Neural Stem Cells Drives Tumorigenesis which can be Ameliorated by Targeting the cAMP Response Element Binding (CREB) Protein(Oxford University Press, 2018-10)BACKGROUND: Hyperactivation of phosphoinositide 3-kinase (PI3K) signaling is common in cancers, but the precise role of the pathway in glioma biology remains to be determined. Some understanding of PI3K signaling mechanisms in brain cancer comes from studies on neural stem/progenitor cells (NSPCs), where signals transmitted via the PI3K pathway cooperate with other intracellular pathways and downstream transcription factors to regulate critical cell functions. METHODS: To investigate the role of the PI3K pathway in glioma initiation and development, we generated a mouse model targeting the inducible expression of a PIK3CAH1047A oncogenic mutant and deletion of the PI3K negative regulator, phosphatase and tensin homolog (PTEN), to NSPCs. RESULTS: Expression of a Pik3caH1047A was sufficient to generate tumors with oligodendroglial features, but simultaneous loss of PTEN was required for the development of invasive, high-grade glioma. Pik3caH1047A-PTEN mutant NSPCs exhibited enhanced neurosphere formation which correlated with increased Wnt signaling, while loss of cAMP response element binding protein (CREB) in Pik3caH1047A-Pten mutant tumors led to longer symptom-free survival in mice. CONCLUSION: Taken together, our findings present a novel mouse model for glioma demonstrating that the PI3K pathway is important for initiation of tumorigenesis and that disruption of downstream CREB signaling attenuates tumor expansion.
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ItemNo Preview AvailableCorrection: Does Malaria Affect Placental Development? Evidence from In Vitro Models(Public Library of Science (PLoS), 2013)
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ItemNo long-term evidence of hyporesponsiveness after use of pneumococcal conjugate vaccine in children previously immunized with pneumococcal polysaccharide vaccine(Elsevier, 2016-06)Background: A randomized controlled trial in Fiji examined the immunogenicity and effect on nasopharyngeal carriage after 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) in infancy followed by 23-valent pneumococcal polysaccharide vaccine (23vPPV; Pneumovax) at 12 months of age. At 18 months of age, children given 23vPPV exhibited immune hyporesponsiveness to a micro-23vPPV (20%) challenge dose in terms of serotype-specific IgG and opsonophagocytosis, while 23vPPV had no effect on vaccine-type carriage. Objective: This follow-up study examined the long-term effect of the 12-month 23vPPV dose by evaluating the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) administration 4 to 5 years later. Methods: Blood samples from 194 children (now 5-7 years old) were taken before and 28 days after PCV13 booster immunization. Nasopharyngeal swabs were taken before PCV13 immunization. We measured levels of serotype-specific IgG to all 13 vaccine serotypes, opsonophagocytosis for 8 vaccine serotypes, and memory B-cell responses for 18 serotypes before and after PCV13 immunization. Results: Paired samples were obtained from 185 children. There were no significant differences in the serotype-specific IgG, opsonophagocytosis, or memory B-cell response at either time point between children who did or did not receive 23vPPV at 12 months of age. Nasopharyngeal carriage of PCV7 and 23vPPV serotypes was similar among the groups. Priming with 1, 2, or 3 PCV7 doses during infancy did not affect serotype-specific immunity or carriage. Conclusion: Immune hyporesponsiveness induced by 23vPPV in toddlers does not appear to be sustained among preschool children in this context and does not affect the pneumococcal carriage rate in this age group.
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ItemNo Preview AvailablePrevalence and risk factors for symptoms of common mental disorders in early and late pregnancy in Vietnamese women: A prospective population-based study(Elsevier, 2013-04-05)BACKGROUND: Little is known about the prevalence of and risk factors for common mental disorders (CMD) in pregnant women in low-income countries. The aim of this study was to establish the prevalence of and psychosocial risk factors for clinically significant symptoms of CMD in early and late pregnancy in women in rural Viet Nam. METHODS: A population-based sample of women was surveyed in early and late pregnancy. CMD were assessed by the Edinburgh Postnatal Depression Scale-Viet Nam Validation and psychosocial risks by study-specific structured interviews. RESULTS: In total 497/523 (97%) eligible women were recruited and 419 (84%) provided complete data. Prevalence of CMD only in early pregnancy was 22.4% (95% CI 18.4-26.4); only in late pregnancy was 10.7% (95% CI 7.8-13.7) and at both assessment waves was 17.4% (95% CI 13.8-21.1). Non-economic and economic coincidental life adversity, intimate partner violence, past pregnancy loss, and childhood abuse were positively associated with persistent antenatal CMD. Older age, having a preference for the baby's sex, and nulli- or primiparity were risk factors for CMD in early pregnancy. CONCLUSIONS: Persistent antenatal CMD are prevalent in rural areas of Viet Nam. Psychosocial risk factors play a major role in this significant public health problem.
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ItemNo Preview AvailableIntimate partner violence and perinatal common mental disorders among women in rural Vietnam(Oxford University Press, 2013-03-01)INTRODUCTION: Intimate partner violence against women (IPV) is regarded increasingly as a public health problem worldwide. The overall aim of this study was to examine the associations between different exposures to IPV and women's mental health during pregnancy and after childbirth in rural Vietnam. METHODS: This was a secondary analysis of data generated in a community-based longitudinal investigation in which a cohort of pregnant women were recruited and followed until 6 months after childbirth. Different forms of IPV were measured by the Intimate Partner Violence section of the WHO Multi-Country Study on Women's Health and Domestic Violence Against Women questionnaire. The Edinburgh Postnatal Depression Scale-Vietnam Validation was used to assess symptoms of the common perinatal mental disorders of depression and anxiety (CPMD). RESULTS: Overall, 497 women were recruited and complete data were available from 417 (83.9%). Exposure to either lifetime or perinatal IPV including emotional abuse, physical violence and sexual violence was associated with increased CPMD symptoms (adjusted odds ratio, OR, ranges 1.3-14.3) and suicidal thoughts (OR ranges 4.7-6.1) in women during pregnancy and after childbirth. Experiencing more than one form of IPV increased the magnitude of the association between IPV and CPMD symptoms and thoughts of suicide. CONCLUSION: It is clearly essential in this and other resource-constrained settings to address emotional, physical and sexual violence perpetrated by an intimate partner in any strategies to reduce the risk of perinatal mental health problems in women.
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ItemNo Preview AvailableEffects of Daily Iron Supplementation in 2- to 5-Year-Old Children: Systematic Review and Meta-analysis(American Academy of Pediatrics, 2013-04-01)BACKGROUND AND OBJECTIVES: Iron deficiency (ID) is the most common cause of anemia worldwide. The prevalence is highest among preschool-aged children. Iron is widely administered to children with or at risk for ID, but evidence of benefit among 2- to 5-year-old children has not been evaluated by systematic review. We summarize the evidence for the benefit and safety of daily iron supplementation with regard to hematologic, growth, and cognitive parameters in 2 to 5 year olds. METHODS: Electronic databases, regional databases, thesis repositories, gray literature, and references of studies and previous reviews were searched. We included randomized controlled trials that compared daily oral iron supplementation with control in 2 to 5 year olds. A random-effects meta-analysis was used to synthesize predefined outcomes reported by at least 2 studies. RESULTS: Of 9169 references, 15 studies met the inclusion criteria, none of which were at low risk of bias. Children receiving iron supplementation had a mean end point hemoglobin of 6.97 g/L (P < .00001; I(2) = 82%) greater than controls, whereas mean end point ferritin was 11.64 µg/L (P < .0001; I(2) = 48%) greater. No trials reported the effects of iron supplementation on ID or iron deficiency anemia, and only one reported on anemia. Limited evidence suggested that iron supplementation produced a small improvement in cognitive development but had no effect on physical growth. CONCLUSIONS: In 2 to 5 year olds, daily iron supplementation increases hemoglobin and ferritin. There is a concerning lack of data on the effect of iron supplementation on clinically important outcomes including anemia, ID anemia, ID, and cognitive development. Additional interventional studies in this age group are needed.
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ItemNo Preview AvailableLow Risk of Japanese Encephalitis in Short-Term Australian Travelers to Asia(WILEY-BLACKWELL, 2013)The risk of Japanese encephalitis (JE) in travelers is unknown. In this prospective study, we investigated the incidence of JE in 387 short-term Australian travelers visiting Asia over a 32-month period from August 2007 to February 2010 by performing pre- and post-travel antibody testing. No travelers were infected with JE virus during travel, indicating a low risk of infection for short-term travelers.
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ItemNo Preview AvailableImprovements in patient care: videoconferencing to improve access to interpreters during clinical consultations for refugee and immigrant patients(CSIRO Publishing, 2015)OBJECTIVE: To demonstrate the suitability of accessing interpreters via videoconference for medical consultations and to assess doctor and patient perceptions of this compared with either on-site or telephone interpreting. METHODS: We assessed the suitability and acceptability of accessing interpreters via videoconference during out-patient clinical consultations in two situations: (i) when the doctor and patient were in a consulting room at a central hospital and the interpreter sat remotely; and (ii) when the doctor, patient and interpreter were each at separate sites (during a telehealth consultation). The main outcome measures were patient and doctor satisfaction, number of problems recorded and acceptability compared with other methods for accessing an interpreter. RESULTS: Ninety-eight per cent of patients were satisfied overall with the use of an interpreter by video. When comparing videoconference interpreting with telephone interpreting, 82% of patients thought having an interpreter via video was better or much better, 15% thought it was the same and 3% considered it worse. Compared with on-site interpreting, 16% found videoconferencing better or much better, 58% considered it the same and 24% considered it worse or much worse. CONCLUSIONS: The present study has demonstrated that accessing an interpreter via videoconference is well accepted and preferred to telephone interpreting by both doctors and patients.
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ItemEfficacy and Safety of Daily Iron Supplementation in Children: Lessons from Three Systematic Reviews and Meta-analyses of Randomized Controlled Trials(SCIENCEDOMAIN International, 2015)Objectives: 47% of pre-school children and 25% of school-aged children are anaemic. Daily iron supplementation remains a key anaemia control intervention, but benefits and safety in children are debated. We systematically reviewed evidence for daily iron supplementation in 4–23m, 2-5y and 5-12y children. Methods: Separate searches and systematic-reviews/meta-analyses were performed for each age-group. Electronic databases and other sources were searched for randomized controlled trials comparing daily iron supplementation with control. Random-effects meta-analysis was used. Risk-of-bias was estimated using the Cochrane tool. Results: For children 4-23m, 2-5y and 5-12y respectively we identified 9533, 9169 and 16501 citations, from which 35, 15 and 32 eligible studies were identified, of which 9, 0 and 4 were at low overall risk-of-bias. Iron improved haemoglobin and ferritin and, in 4-23 m and 5-12y, reduced anaemia and iron deficiency. In 5-12y, iron improved global cognitive scores (SMD 0.50 [0.11, 0.90], p = 0.01) and in anaemic children, IQ (MD 4.55 [0.16, 8.94], p = 0.04). In 2-5y, limited data suggested a small improvement from iron in cognitive performance. No benefit was evident in 4-23 m (Bayley’s mental development index: MD 1·65 [–0·63, 3·94]) overall but was seen in iron deficient children (MD 5.90 [1.91, 10.00], p=0.005). Iron did not benefit growth in 4-23 m or 2-5y, but did improve growth in 5-12y. Vomiting and fever were increased in 4-23m receiving iron. Conclusions: Although supplementation iron improves cognition in older children or children with ID, evidence of non-haematologic benefit in pre-school children is inadequate. Further research is needed to enable guideline development.
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ItemEffects of daily iron supplementation in primary-school-aged children: systematic review and meta-analysis of randomized controlled trials(CMA-CANADIAN MEDICAL ASSOC, 2013-11-19)BACKGROUND: Anemia is an important public health and clinical problem. Observational studies have linked iron deficiency and anemia in children with many poor outcomes, including impaired cognitive development; however, iron supplementation, a widely used preventive and therapeutic strategy, is associated with adverse effects. Primary-school-aged children are at a critical stage in intellectual development, and optimization of their cognitive performance could have long-lasting individual and population benefits. In this study, we summarize the evidence for the benefits and safety of daily iron supplementation in primary-school-aged children. METHODS: We searched electronic databases (including MEDLINE and Embase) and other sources (July 2013) for randomized and quasi-randomized controlled trials involving daily iron supplementation in children aged 5-12 years. We combined the data using random effects meta-analysis. RESULTS: We identified 16 501 studies; of these, we evaluated 76 full-text papers and included 32 studies including 7089 children. Of the included studies, 31 were conducted in low- or middle-income settings. Iron supplementation improved global cognitive scores (standardized mean difference 0.50, 95% confidence interval [CI] 0.11 to 0.90, p = 0.01), intelligence quotient among anemic children (mean difference 4.55, 95% CI 0.16 to 8.94, p = 0.04) and measures of attention and concentration. Iron supplementation also improved age-adjusted height among all children and age-adjusted weight among anemic children. Iron supplementation reduced the risk of anemia by 50% and the risk of iron deficiency by 79%. Adherence in the trial settings was generally high. Safety data were limited. INTERPRETATION: Our analysis suggests that iron supplementation safely improves hematologic and nonhematologic outcomes among primary-school-aged children in low- or middle-income settings and is well-tolerated.