Immunogenicity of meningococcal PorA formulations encapsulated in biodegradable microspheres.

The purpose of our study was to investigate the possibility to microencapsulate liposomes and meningococcal outer membrane vesicles (OMV), both containing neisserial pore protein A (PorA), in biodegradable dextran- and mannan-based microspheres and to study the immunogenicity of the encapsulated PorA formulations. PorA-liposomes and OMV were encapsulated in dextran- or mannan-based microspheres by using an aqueous two-phase system consisting of a polyethylene glycol solution and a methacrylated dextran or mannan solution. The formulations were characterized for size distribution, PorA structure and antigen recovery after release. Calcein-containing model liposomes were used to establish the encapsulation efficiency and release profiles from both types of microspheres. The immunogenicity of the PorA-containing formulations was determined in mice after subcutaneous immunization. Liposomes were encapsulated in dextran and mannan microspheres with a high efficiency (70-90%). Calcein liposomes, after a 5-day lag period, exhibited apparent zero-order release kinetics from both types of microspheres between Days 5 and 10 of incubation in vitro. The total release was 80 and 100% from mannan and dextran microspheres, respectively. The trimeric PorA conformation was preserved in the released liposomes and OMV and the antigen was partly recovered. The immunogenicity of PorA-liposomes and OMV encapsulated in dextran or mannan microspheres was preserved. In conclusion, PorA-liposomes and OMV could be encapsulated in dextran- and mannan-based microspheres with high efficiency. The immunogenicity of encapsulated antigen was preserved.     

THE PRIMARY STRUCTURE OF MUSKRAT PANCREATIC RIBONUCLEASE

Pancreatic ribonuclease from muskrat (Ondatra zibethica) was isolated and its amino acid sequence was determined from tryptic digests of the performic acid-oxidized and the reduced and aminoethylated enzyme. The peptides have been positioned in the sequence by homology with other ribonucleases. This could be done unambiguously for all peptides except Arg-Arg (tentative position 32–33) and Ser-Arg (tentative position 75–76). The amino acid sequences of the peptides were determined by the dansyl-Edman method, with the exception of residues 23–25 and 99–102, which were positioned by homology. The enzyme differs in 38 positions from the enzyme from rat and in 31–42 positions from other mammalian pancreatic ribonucleases, while rat ribonuclease differs at 44–52 positions from the other enzymes. These data point to a common ancestry of the enzymes from muskrat and rat and an increased evolution rate of rat ribonuclease after divergence of the ancestors of both species. Muskrat ribonuclease contains no carbohydrate, although the enzyme possesses a recognition site for carbohydrate attachment in the sequence Asn- Val-Thr (62–64).     

The short-run causal effect of tumor detection and treatment on psychosocial well-being,work, and income

This paper estimates the short-run causal effect of tumor detection and treatment on psychosocial well-being, work and income. Tumor detection can be considered as a random event, so that we can compare individuals’ average outcomes in the year of diagnosis with the year before. We argue for using panel data estimation techniques that enable us to control for observed and unobserved information intrinsic to the individual and time constants. We use data of a national representative panel in the Netherlands that includes health survey information and data on work, education, and income between 2007 and 2012. Our findings show differences in the psychosocial dysfunction of men and women in response to tumor detection and treatment. Women, not men, are decreasingly likely to participate in the labor force as a result of malignant tumor detection, while no significant effects are found on her personal or household income. We also demonstrate that fixed effects panel data models are superior to matching techniques.     

Sacral Neuromodulation for the Treatment of Chronic Functional Anorectal Pain: A Single Center Experience

Introduction:   Treatment of functional anorectal pain disorders remains a challenge. The purpose of this study is to describe a single center experience with sacral neuromodulation for the treatment of chronic functional anorectal pain.
Methods:   This is a retrospective study based on prospectively collected data of patients treated with sacral neuromodulation for functional anorectal pain from April 2005 to August 2008. Symptoms were analyzed using a visual analog scale pain score (0 to 10). A 7-point Likert scale was used to rate global perceived effect. All patients had a percutaneous nerve evaluation and subsequent test stimulation to assess sacral neuromodulation outcome prior to permanent implantation. Patients were eligible for permanent sacral neuromodulation in case of a pain score <3 during test stimulation and/or >50% decrease in the pain score compared to baseline.
Results:   Nine patients (2 males) were included in this study. Mean age was 53.8 years (27.6 to 74.0). Four patients (1 male) had successful test stimulation and were eligible for permanent implantation. Median pain score decreased from 8.0 (6.0 to 9.0) to 1.0 (0 to 2.0). All patients experienced a lasting improvement during the follow-up till 24 months. Global perceived effect in successful patient was 1 (completely recovered) in one patient and 2 (much improved) in three patients.
Conclusion:   This study showed that sacral neuromodulation can be a successful treatment for functional anorectal pain not responding to other treatments. Improvement obtained during test stimulation is a good predictor (diagnostic) for sustained success of permanent sacral neuromodulation.