An adenoviral vector deleted for all viral coding sequences results in enhanced safety and extended expression of a leptin transgene

Adenoviral (Ad)-mediated in vivo gene transfer and expression are limited in part by cellular immune responses to viral-encoded proteins and/or transgene immunogenicity. In an attempt to diminish the former responses, we have previously developed and described helper-dependent (HD) Ad vectors in which the viral protein coding sequences are completely eliminated. These HD vectors have up to 37 kb insert capacity, are easily propagated in a Cre recombinase-based system, and can be produced to high concentration and purity (>99.9% helper-free vector). In this study, we compared safety and efficacy of leptin gene delivery mediated by an HD vector (HD-leptin) and a first-generation E1-deleted Ad vector (Ad-leptin) in normal lean and ob/ob (leptin-deficient) mice. In contrast to evidence of liver toxicity, inflammation, and cellular infiltration observed with Ad-leptin delivery in mice, HD-leptin delivery was associated with a significant improvement in associated safety/toxicity and resulted in efficient gene delivery, prolonged elevation of serum leptin levels, and associated weight loss. The greater safety, efficient gene delivery, and increased insert capacity of HD vectors are significant improvements over current Ad vectors and represent favorable features especially for clinical gene therapy applications.     

Health care costs and costs associated with changes in work productivity among persons with systemic lupus erythematosus

Objective

To estimate health care costs and costs associated with changes in work productivity among persons with systemic lupus erythematosus (SLE) in the US.

Methods

Data were derived from the University of California, San Francisco Lupus Outcomes Study. Participants provided information on their health care resource use and employment. Cost estimates were derived for both direct health care costs and costs related to changes in work productivity. Direct health care costs included costs for hospitalizations, emergency department services, physician visits, outpatient surgical procedures, dialysis, and medications. Productivity costs were estimated by measuring changes in hours of work productivity since diagnosis of SLE; these estimates were also compared with normal US population data.

Results

For the total population of participants, the mean annual direct cost was $12,643 (2004 US dollars). The mean annual productivity cost for subjects of employment age (≥18 and <65 years) was $8,659. The mean annual total cost (direct and productivity) for subjects of employment age was $20,924. Regression results showed that greater disease activity, longer disease duration, and worse physical and mental health were significant predictors of higher direct costs; older age predicted lower direct costs. Older age, greater disease activity, and worse physical and mental health status were significant predictors of higher costs due to changes in work productivity.

Conclusion

Both direct health care costs and costs associated with changes in work productivity are substantial and both represent important contributors to the total costs associated with SLE.     

HIV-Related Stigma among People with HIV and their Families: A Qualitative Analysis

We examined the interconnectedness of stigma experiences in families living with HIV, from the perspective of multiple family members. Semi-structured interviews were conducted with 33 families (33 parents with HIV, 27 children under age 18, 19 adult children, and 15 caregivers). Parents were drawn from the HIV Cost and Services Utilization Study, a representative sample of people in care for HIV in US. All of the families recounted experiences with stigma, including 100% of mothers, 88% of fathers, 52% of children, 79% of adult children, and 60% of caregivers. About 97% of families described discrimination fears, 79% of families experienced actual discrimination, and 10% of uninfected family members experienced stigma from association with the parent with HIV. Interpersonal discrimination seemed to stem from fears of contagion. Findings indicate a need for interventions to reduce HIV stigma in the general public and to help families cope with stigma.     

Lactobacillus rhamnosus GG in adenoid tissue: Double-blind,placebo-controlled,randomized clinical trial

Conclusion: Lactobacillus rhamnosus GG (L.GG) was present in all adenoids of children receiving the L. GG product. However, since L.GG was also found from the placebo group, one cannot confirm its effect on the occurrence of rhinovirus (RV) or enterovirus (EV). Objectives: The present study was conducted to determine whether a 3-week oral consumption of L.GG would lead to presence of the probiotic in adenoid tissue. Furthermore, nasopharyngeal RV and EV findings and symptom data were investigated. Method: The tissue samples were collected from 40 children aged 1–5 years about to undergo adenotomy due to recurrent acute/secretory otitis media, chronic rhinitis, or recurrent sinusitis after a 3-week daily consumption of L.GG (n = 20) or placebo (n = 20). Strain-specific real-time PCR was used to detect RV, EV, and L.GG in adenoid tissue. Results: L.GG was recovered in the adenoid sample in 100% of children in the L.GG group and in 76% in the placebo group (p = 0.07). Both RV and EV were found in 31% of children in the L.GG group and in 18% of children in the placebo group (p = 0.67). The majority of the positive samples were positive for both RV and EV. Study diaries showed no differences in symptoms between the groups.     

Does age influence the success of intra-tympanic steroid treatment in idiopathic sudden deafness?

Conclusions: The present study shows that AGE, DELAY, and PTA_PRE may be considered factors influencing therapeutic success in intra-tympanic steroid therapy. Objective: The aim of the study is to evaluate the relationship between the therapeutic success of intra-tympanic prednisolone therapy and age, in patients affected by idiopathic sudden sensorineural hearing loss (ISSNHL), considering the influence of factors such as delay, gender, and pure tone average (PTA) pre-therapy. Method: This retrospective study involved 402 consecutive patients, affected by unilateral ISSNHL between January 2009 and January 2014. Patients were divided into two groups based on age: group one with 94 patients aged over 65 years and group two with all 402 patients enrolled in the study, including those over 65. Results: PTA recorded before the beginning of the therapy (PTA_PRE) in group one was worse than for group two. In both groups the therapy was significantly effective in improving hearing thresholds, even if PTA_PRE was significant and negatively correlated with success rate. This effect disappeared within the population over 65. On average, each day of DELAY from the onset of hearing loss to the beginning of therapy cuts almost 2% of the possibility to recover. AGE was negative and significant when specified continuously for group two.     

Avoidance Symptom Presentation of Preschoolers Exposed to Intimate Partner Violence in a Group Therapy Setting

Post-traumatic stress disorder (PTSD) is a serious problem for children exposed to intimate partner violence (IPV). Recent changes to diagnostic criteria for PTSD include a reduction in avoidance symptom criteria from three to one and the separation of emotional numbing from avoidance symptoms, thus creating a need to better understand how avoidance symptoms of PTSD present themselves in young children. This study evaluated 56 children aged four to six as they participated in an intervention for mothers and children exposed to IPV. Therapists documented behaviours indicative of avoidance symptoms during group sessions. Data were analysed and coded into symptom categories and thematically emergent domains. Results demonstrated that avoidance symptoms fell into three separate categories: physical avoidance, emotional avoidance, and changing topics. Additionally, the data support the Diagnostic and Statistical Manual of Mental Disorders (5th edition) change to remove emotional numbing from the avoidance symptom category. These results give insight into how to develop more targeted treatments for PTSD as well as improve the assessment and diagnosis of PTSD symptoms in preschoolers.     

Research Priorities for Economic Analyses of Prevention: Current Issues and Future Directions

In response to growing interest in economic analyses of prevention efforts, a diverse group of prevention researchers, economists, and policy analysts convened a scientific panel, on “Research Priorities in Economic Analysis of Prevention” at the 19th annual conference of the Society for Prevention Research. The panel articulated four priorities that, if followed in future research, would make economic analyses of prevention efforts easier to compare and more relevant to policymakers and community stakeholders. These priorities are: (1) increased standardization of evaluation methods, (2) improved economic valuation of common prevention outcomes, (3) expanded efforts to maximize evaluation generalizability and impact as well as (4) enhanced transparency and communicability of economic evaluations. In this paper, we define three types of economic analyses in prevention, provide context and rationale for these four priorities as well as related sub-priorities, and discuss the challenges inherent in meeting them.     

Characterization of eleven polymorphic microsatellite markers for leafhoppers of the genus Aphrodes (Hemiptera: Cicadellidae)

Eleven microsatellite markers were developed for the leafhoppers of the genus Aphrodes using shotgun pyrosequencing and will be used to study the genetic diversity, population structure and gene flow within and between species in this genus in order to assess their conservation status. The number of alleles per locus ranged from 3 to 10, while observed and expected heterozygosity values varied from 0.421–1.000 to 0.542–0.876, respectively. Cross-species amplification was successful among the four congeners.