HIV vaccines should elicit immune responses at both the mucosal portals of entry to block transmission and systemic compartments to clear disseminated viruses. Co-delivery of mucosal adjuvants has been shown to be essential to induce effective mucosal immunity by non-replicating vaccines. A novel cytokine, GIFT4, engineered by fusing GM-CSF and interleukin-4, was previously found to simulate B cell proliferation and effector function. Herein a membrane-anchored form of GIFT4 was constructed by fusing a glycolipid (GPI)-anchoring sequence and incorporated into Env-enriched HIV virus-like particles (VLPs) as a molecular adjuvant. Guinea pigs were immunized with the resulting HIV VLPs through an intramuscular priming-intranasal boosting immunization route. The GIFT4-containing VLPs induced higher levels of systemic antibody responses with significantly increased binding avidity and improved neutralizing breadth and potency to a panel of selected strains, as well as higher levels of IgG and IgA at several mucosal sites. Thus, the novel GPI-GIFT4-containging VLPs have the potential to be developed into a prophylactic HIV vaccine. Incorporation of GPI-anchored GIFT4 into VLPs as a molecular adjuvant represents a novel approach to increase their immunogenicity.

Background: Diverse cognitive functions and behaviors have been monitored in the two sub-types of attention deficit/hyperactivity disorder (ADHD) including the combined type and the inattentive type. Objectives: Previous studies have shown that ADHD children have problems in visual memory, and short and long-term use of methylphenidate (MPH) improves these functions, but fewer studies have been done on the inattentive subgroup, namely attention deficit disorder (ADD). Due to the different cognitive functions in these two ADHD subgroups, this study was done to investigate the long-term use of MPH on the visual memory of ADD children. Methods: A 4-week experimental clinical trial using MPH (1 mg/kg/dose) was conducted. Participants were 20 children aged 6 -11 years with ADD that came to the Rouzbeh Clinic in Tehran in 2010. Cambridge neuropsychological test automated battery (CANTAB) tests of visual memory were used for assessment. Results: The long-term use of MPH improved 12 aspects of paired associated learning (PAL) such as first-trial memory score, the number of mean mistakes to success and mean efforts to success (P < 0.05). However, MPH did not improve the stages completed in the first trial, the total errors, and the total errors adjusted in the three-shape step of PAL (P > 0.05). MPH also improved all aspects of pattern recognition memory (PRM) (P < 0.05) and the mean correct latency of spatial recognition memory (SRM) (P < 0.05). However, MPH had no effect on delayed matching to sample (DMS) (P > 0.05). Conclusions: MPH improved performance on the PAL, PRM, and SRM visual evaluating tests of ADD patients. Nevertheless, the patients did not show any improvement in the DMS test. In comparison with previous studies, our results would suggest that MPH has similar effects on the visual memory of ADD and ADHD patients.

INTRODUCTION: Use of stress ulcer prophylaxis (SUP), administration of acid suppressive therapies (AST) to prevent nosocomial gastrointestinal bleeding, is rampant outside of intensive care units despite a lack of data supporting its efficacy. Inappropriate use rates as high as 90% have been reported nationally. Following this, many times AST is inappropriately continued at discharge as well. Potential side effects include vitamin B12 deficiency, osteoporosis, Clostridium difficile infection, pneumonia and CKD. A multidisciplinary educational approach has been used to improve prescribing patterns in other disease states. METHODS: We aimed to decrease inappropriate stress ulcer prophylaxis using a multidisciplinary academic detailing team on an inpatient internal medicine teaching service (IIMTS). Using the quality improvement model plan-do-study-act (PDSA), we retrospectively collected baseline data on inappropriate SUP use on IIMTS over one month. We then implemented PDSA 1: academic detailing, whereby a multidisciplinary team (clinical pharmacist plus internist), gave teaching sessions on appropriate SUP indications to IM residents. With PDSA 2, we introduced a hard stop into IIMTS note templates. We collected prospective post-intervention data for one month after each intervention. RESULTS: Pre-intervention, 95 patients received AST, of which 68 (71%) were receiving AST prior to admission and 27 were prescribed AST upon admission. Overall rates of inpatient initiation of SUP decreased from 25.4% to 16.4% and then 5.4% from the pre-intervention phase to PDSA 1 and PDSA 2 respectively. Rates of inappropriate SUP use also decreased from 8.4% to 7.1% and then 4% respectively. CONCLUSION: Academic detailing as a means to change clinician practices through evidence-based medicine has been shown to have a risk difference of up to 16% in the literature. Furthermore, the addition of a hard stop has been shown to effectively make these changes more permanent. These strategies were successfully used in our inpatient setting to decrease inappropriate AST use, subsequently translating to a reduction in long term complications and cost accrual.