Congenital rubella syndrome (CRS) in Vietnam 2011–2012—CRS epidemic after rubella epidemic in 2010–2011

BackgroundRubella is endemic in Vietnam with epidemics occurring every 4–5 years. In 2011, Vietnam experienced the large nationwide rubella epidemic. During the rubella epidemic, many infants born with congenital rubella syndrome (CRS) were identified and reported from the neonatal units or cardiology departments of the national hospitals. To understand the burden of CRS, National Expanded Program on Immunization (NEPI) established sentinel CRS surveillance system.MethodThree national paediatric hospitals in Hanoi and Ho Chi Minh City (HCMC) were selected as CRS sentinel surveillance sites. Blood specimens from the infants were collected for rubella specific IgM and ELISA testing was performed at the national measles and rubella laboratory.ResultsFrom January 2011 to December 2012, 424 infants with suspected CRS were identified and reported. Among them 406 (96%) had specimens obtained, 284 (70%) cases were IgM positive including 279 laboratory confirmed CRS and 5 Congenital Rubella Infection (CRI). 13 cases were clinically confirmed and 127 (30%) were discarded. Total 292 infants were confirmed as CRS. Of the 292 infants with CRS, 69% of mothers had a history of “fever and rash” during pregnancy, of which 85% was in the first trimester. The most common clinical defects were congenital heart disease and cataract(s). However, 81.9% of the infants had a combination of major and minor signs and symptoms. Low birth weight in full term infants with confirmed CRS was observed in 114 infants (39%).ConclusionsThe newly established CRS sentinel surveillance system documented the significant burden of CRS in Vietnam and provided evidence to the policy makers for the introduction of rubella containing vaccine (RCV) into Vietnam. This report highlights the importance of countries with rubella epidemic to establish CRS surveillance rapidly in order to support the introduction of RCV into the routine Expanded Programme on Immunization (EPI) immunization.     

Estimating the herd immunity effect of rotavirus vaccine

IntroductionDiarrhea is one of the leading causes of death in children under 5, and an estimated 39% of these deaths are attributable to rotavirus. Currently two live, oral rotavirus vaccines have been introduced on the market; however, the herd immunity effect associated with rotavirus vaccine has not yet been quantified. The purpose of this meta-analysis was to estimate the herd immunity effects associated with rotavirus vaccines.MethodsWe performed a systematic literature review of articles published between 2008 and 2014 that measured the impact of rotavirus vaccine on severe gastroenteritis (GE) morbidity or mortality. We assessed the quality of published studies using a standard protocol and conducted meta-analyses to estimate the herd immunity effect in children less than one year of age across all years presented in the studies. We conducted these analyses separately for studies reporting a rotavirus-specific GE outcome and those reporting an all-cause GE outcome.ResultsIn studies reporting a rotavirus-specific GE outcome, four of five of which were conducted in the United States, the median herd effect across all study years was 22% [19–25%]. In studies reporting an all-cause GE outcome, all of which were conducted in Latin America, the median herd effect was 24.9% [11–30%].ConclusionsThere is evidence that rotavirus vaccination confers a herd immunity effect in children under one year of age in the United States and Latin American countries. Given the high variability in vaccine efficacy across regions, more studies are needed to better examine herd immunity effects in high mortality regions.     

Systemic immune responses to an inactivated,whole H9N2 avian influenza virus vaccine using class B CpG oligonucleotides in chickens

Commercial vaccines against avian influenza viruses (AIV) in chickens consist mainly of inactivated AIV, requiring parenteral administration and co-delivery of an adjuvant. Limitations in T helper 1 or T helper 2 biased responses generated by these vaccines emphasize the need for alternative, more efficacious adjuvants. The Toll-like receptor (TLR) 21 ligand, CpG oligodeoxynucleotides (ODN), has been established as immunomodulatory in chickens. Therefore, the objective of this study was to investigate the adjuvant potential of high (20 μg) and low (2 μg) doses of CpG ODN 2007 (CpG 2007) and CpG ODN 1826 (CpG 1826) when administered to chickens with a formalin-inactivated H9N2 AIV. Antibody responses in sera were evaluated in 90 specific pathogen free (SPF) chickens after intramuscular administration of vaccine formulations at 7 and 21 days post-hatch. Antibody responses were assessed based on haemagglutination inhibition (HI) and virus neutralization (VN) assays; virus-specific IgM and IgY antibody responses were evaluated by ELISA. The results suggest that the vaccine formulation containing low dose CpG 2007 was significantly more effective at generating neutralizing (both HI and VN) responses than formulations with high or low doses of CpG 1826 or high dose CpG 2007. Neutralizing responses elicited by low dose CpG 2007 significantly exceeded those generated by a squalene-based adjuvanted vaccine formulation during peak responses. A significantly higher IgM response was elicited by the formulation containing low dose CpG 2007 compared to high and low doses of 1826. Although the low dose of CpG 2007 elicited a higher IgY response than CpG 1826, the difference was not statistically significant. In conclusion, 2 μg of CpG 2007 is potentially promising as a vaccine adjuvant when delivered intramuscularly with inactivated H9N2 virus to chickens. Future studies may be directed at determining the mucosal antibody responses to the same vaccine formulations.     

Functional Status Is Associated With 30-Day Potentially Preventable Hospital Readmissions After Inpatient Rehabilitation Among Aged Medicare Fee-for-Service Beneficiaries

ObjectivesTo determine the association between patients' functional status at discharge from inpatient rehabilitation and 30-day potentially preventable hospital readmissions. A secondary objective was to examine the conditions resulting in these potentially preventable readmissions.DesignRetrospective cohort study.SettingInpatient rehabilitation facilities submitting claims to Medicare.ParticipantsNational cohort (N=371,846) of inpatient rehabilitation discharges among aged Medicare fee-for-service beneficiaries in 2013 to 2014. The average age was 79.1±7.6 years. Most were women (59.7%) and white (84.5%).InterventionsNot applicable.Main Outcome Measures(1) Observed rates and adjusted odds of 30-day potentially preventable hospital readmissions after inpatient rehabilitation and (2) primary diagnoses for readmissions.ResultsThe overall rate of any 30-day hospital readmission after inpatient rehabilitation was 12.4% (n=46,265), and the overall rate of potentially preventable readmissions was 5.0% (n=18,477). Functional independence was associated with lower observed rates and adjusted odds ratios for potentially preventable readmissions. Observed rates for the highest versus lowest quartiles within each functional domain were as follows: self-care: 3.4% (95% confidence interval [CI], 3.3–3.5) versus 6.9% (95% CI, 6.7–7.1), mobility: 3.3% (95% CI, 3.2–3.4) versus 7.2% (95% CI, 7.0–7.4), and cognition: 3.5% (95% CI, 3.4–3.6) versus 6.2% (95% CI, 6.0–6.4), respectively. Similarly, adjusted odds ratios were as follows: self-care: .70 (95% CI, .67–.74), mobility: .64 (95% CI, .61–.68), and cognition: .84 (95% CI, .80–.89). Infection-related conditions (44.1%) were the most common readmission diagnoses followed by inadequate management of chronic conditions (31.2%) and inadequate management of other unplanned events (24.7%).ConclusionsFunctional status at discharge from inpatient rehabilitation was associated with 30-day potentially preventable readmissions in our sample of aged Medicare beneficiaries. This information may help identify at-risk patients. Future research is needed to determine whether follow-up programs focused on improving functional independence will reduce readmission rates.     

Exploring relation types for literature-based discovery

Objective Literature-based discovery (LBD) aims to identify “hidden knowledge” in the medical literature by: (1) analyzing documents to identify pairs of explicitly related concepts (terms), then (2) hypothesizing novel relations between pairs of unrelated concepts that are implicitly related via a shared concept to which both are explicitly related. Many LBD approaches use simple techniques to identify semantically weak relations between concepts, for example, document co-occurrence. These generate huge numbers of hypotheses, difficult for humans to assess. More complex techniques rely on linguistic analysis, for example, shallow parsing, to identify semantically stronger relations. Such approaches generate fewer hypotheses, but may miss hidden knowledge. The authors investigate this trade-off in detail, comparing techniques for identifying related concepts to discover which are most suitable for LBD.Materials and methods A generic LBD system that can utilize a range of relation types was developed. Experiments were carried out comparing a number of techniques for identifying relations. Two approaches were used for evaluation: replication of existing discoveries and the “time slicing” approach.¹Results Previous LBD discoveries could be replicated using relations based either on document co-occurrence or linguistic analysis. Using relations based on linguistic analysis generated many fewer hypotheses, but a significantly greater proportion of them were candidates for hidden knowledge.Discussion and Conclusion The use of linguistic analysis-based relations improves accuracy of LBD without overly damaging coverage. LBD systems often generate huge numbers of hypotheses, which are infeasible to manually review. Improving their accuracy has the potential to make these systems significantly more usable.     

Preliminary evidence of disparities in physical activity among adolescents with bipolar disorder

Physical activity can potentially mitigate the symptomatic burden and cardiovascular risk associated with bipolar disorder (BD). Studies have found that adults with BD are less physically active than controls. However, no previous study has examined this topic among adolescents with BD. This study compares physical activity among adolescents with BD vs. healthy controls without major psychiatric disorders, and examines characteristics associated with physical activity among adolescents with BD. Subjects were 86 adolescents with a diagnosis of BD via gold-standard psychiatric interviews, and 50 controls. The Quick Weight, Activity & Excess Screener (WAVE) was used to assess physical activity. Between-group analyses examined for differences in achieving recommended benchmarks for three types of physical activity: working out, “working in” (incidental physical activity), and screen time. Exploratory within-group analyses were based on a median split (high vs. low) of the total physical activity scores among BD adolescents. Adolescents with BD were significantly less likely to report working out regularly (6%) as compared to controls (22%; χ² = 7.98, p = 0.005). There were no significant between-group differences in working in or screen time. BD adolescents with low levels of physical activity were less likely to have a family history of substance use disorder (p = 0.03). Adolescents with BD are less likely than their peers to achieve the recommended benchmark for regular working out. Future studies are warranted to determine what factors explain this difference, and to identify strategies for optimizing physical activity among adolescents with BD.     

Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases

Vision is the sense that we use to navigate the world around us. Thus it is not surprising that blindness is one of people's most feared maladies. Heritable diseases of the retina, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world, collectively affecting as many as one-third of all people over the age of 75, to some degree. For decades, scientists have dreamed of preventing vision loss or of restoring the vision of patients affected with retinal degeneration through drug therapy, gene augmentation or a cell-based transplantation approach. In this review we will discuss the use of the induced pluripotent stem cell technology to model and develop various treatment modalities for the treatment of inherited retinal degenerative disease. We will focus on the use of iPSCs for interrogation of disease pathophysiology, analysis of drug and gene therapeutics and as a source of autologous cells for cell transplantation and replacement.     

Advances in understanding the molecular basis of the first steps in color vision

Serving as one of our primary environmental inputs, vision is the most sophisticated sensory system in humans. Here, we present recent findings derived from energetics, genetics and physiology that provide a more advanced understanding of color perception in mammals. Energetics of cis–trans isomerization of 11-cis-retinal accounts for color perception in the narrow region of the electromagnetic spectrum and how human eyes can absorb light in the near infrared (IR) range. Structural homology models of visual pigments reveal complex interactions of the protein moieties with the light sensitive chromophore 11-cis-retinal and that certain color blinding mutations impair secondary structural elements of these G protein-coupled receptors (GPCRs). Finally, we identify unsolved critical aspects of color tuning that require future investigation.     

Fixation strategies for retinal immunohistochemistry

Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The beauty of numerous images published to date, and the qualitative and quantitative information they provide, indicate that these approaches are fundamentally useful. However, obtaining these images entailed tissue handling and exposure to chemical solutions that differ from normal extracellular fluid in composition, temperature, and osmolarity. Because the differences are large enough to alter intercellular and intracellular signaling in neurons, and because retinae are susceptible to crush, shear, and fray, it is natural to wonder if immunohistochemical and anatomical methods disturb or damage the cells they are designed to examine. Tissue fixation is typically incorporated to guard against this damage and is therefore critically important to the quality and significance of the harvested data. Here, we describe mechanisms of fixation; advantages and disadvantages of using formaldehyde and glutaraldehyde as fixatives during immunohistochemistry; and modifications of widely used protocols that have recently been found to improve cell shape preservation and immunostaining patterns, especially in proximal retinal neurons.     

Hazard identification of cis/trans-zearalenone through the looking-glass

Among the food-related health issues, the presence of contaminants has a prominent role, due to the wide range of exogenous compounds that can occur in food commodities and to their large differences in structure and biological activity. A comprehensive assessment of the related risk is thus actually demanding in terms of time and facilities involved. In this context, the use of computational strategies can be an effective choice for supporting the hazard identification procedure at the early stage. In this work, we focused on the food contaminant zearalenone by comparing the trans and cis isomers, respectively the well-known mycoestrogen and its still largely understudied isomer. We estimated the possible effects exerted by human metabolism on the xenoestrogenicity of cis-ZEN by using a validated in silico strategy based on docking simulations and rescoring procedures. Similarly, the exploitation of the most promising enzymatic detoxifying routes designed for trans-ZEN – which relies on the enzyme lactono hydrolase from Clonostachys rosea – has been assessed for the cis-isomer as well. Our results showed that both isomers can act as functional analogues with respect to xenoestrogenic activity, and several cis-ZEN metabolites with high biological potential have been identified. On the contrary, in spite of the high degree of structural analogy, the cis isomer showed a pattern of interaction with the degrading enzyme in stark contrast with that observed for trans-ZEN. For these reasons, the outcomes presented herein strongly support the inclusion of cis-ZEN in further studies of occurrence, metabolism and bioactivity assessment, and suggest the need for a dedicated handling for the cis isomer in risk assessment studies.