Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccines

A unique multicomponent vaccine against serogroup B meningococci incorporates the novel genome-derived proteins fHbp, NHBA, and NadA that may vary in sequence and level of expression. Measuring the effectiveness of such vaccines, using the accepted correlate of protection against invasive meningococcal disease, could require performing the serum bactericidal assay (SBA) against many diverse strains for each geographic region. This approach is impractical, especially for infants, where serum volumes are very limited. To address this, we developed the meningococcal antigen typing system (MATS) by combining a unique vaccine antigen-specific ELISA, which detects qualitative and quantitative differences in antigens, with PorA genotyping information. The ELISA correlates with killing of strains by SBA and measures both immunologic cross-reactivity and quantity of the antigens NHBA, NadA, and fHbp. We found that strains exceeding a threshold value in the ELISA for any of the three vaccine antigens had ≥80% probability of being killed by immune serum in the SBA. Strains positive for two or more antigens had a 96% probability of being killed. Inclusion of multiple different antigens in the vaccine improves breadth of coverage and prevents loss of coverage if one antigen mutates or is lost. The finding that a simple and high-throughput assay correlates with bactericidal activity is a milestone in meningococcal vaccine development. This assay allows typing of large panels of strains and prediction of coverage of protein-based meningococcal vaccines. Similar assays may be used for protein-based vaccines against other bacteria.     

Mentalizing in economic decision-making

In the Ultimatum Game, participants typically reject monetary offers they consider unfair even if the alternative is to gain no money at all. In the present study, ERPs were recorded while subjects processed different offers of a proposer. In addition to clearly fair and unfair offers, mid-value offers which cannot be easily classified as fair or unfair and therefore involve more elaborate decision making were analyzed. A fast initial distinction between fair and other kinds of offers was reflected by amplitude of the feedback related negativity (FRN). Mid-value offers were associated with longer RTs, and a larger N350 amplitude. In addition, source analyses revealed a specific involvement of the superior temporal gyrus and the inferior parietal lobule during processing of mid-value offers compared to offers categorized clearly as fair or unfair, suggesting a contribution of mentalizing about the intention of the proposer to the decision making process. Taken together, the present findings support the idea that economic decisions are significantly affected by non-rational factors, trying to narrow the gap between formal theory and the real decisional behaviour.     

Irinotecan+cisplatin and irradiation are effective for brain metastases of gastric cancer--two case reports

We treated two patients in whom irinotecan (CPT-11)+cisplatin (CDDP) and irradiation showed efficacy against brain metastases of gastric cancer. CPT-11 and CDDP were administered on days 1 and 15 of a 28-day cycle at 60 mg/m(2) and 30 mg/m(2), respectively. The first patient was a 63-year-old man,who complained of headache and weakness. In March 2003, he was diagnosed as having Stage IV gastric cancer with peritoneal dissemination (T3, Nx, P1) and underwent total gastrectomy with D1 dissection. Chemotherapy with S-1 was continued after surgery. Two years and two months later, a metastatic tumor was found in the upper lobe of the right lung. The protocol was changed to S-1+CDDP, but progression of his disease occurred. The weekly paclitaxel (PTX) therapy was tried instead. Seven months later, he developed headache and weakness, and multiple brain metastases were diagnosed by CT scanning. We performed total brain irradiation (30 Gy) and started CPT-11+CDDP therapy, which was continued on a fortnightly basis at 60 mg/m(2) and 30 mg/m(2), respectively. The brain metastases regressed (PR), and this therapy led to a marked improvement in his quality of life. The second patient was a 78-year-old man, who complained of weakness of the lower extremities and dizziness. In November 2003, he was diagnosed as having stage IB gastric cancer (T2 (ss), N0, P0), and underwent total gastrectomy and splenectomy with D2 dissection. One year and four months later, local recurrence at the anastomosis was detected, as well as a metastatic tumor in the right lung. S-1, S-1+CDDP, and weekly PTX therapy were all tried. One year later, the patient was admitted with weakness and dizziness,and brain metastases were detected by CT scanning. We then performed Cyber Knife treatment and administered CPT-11+CDDP. As a result, his brain metastases partially regressed (PR).     

Safety and efficacy of 5% imiquimod cream for the treatment of skin dysplasia in high-risk renal transplant recipients: randomized, double-blind, placebo-controlled trial

OBJECTIVE: To evaluate the safety and efficacy of 5% imiquimod cream for cutaneous dysplasia in high-risk renal transplant recipients. DESIGN: A randomized, blinded, placebo-controlled study comparing treated with control skin. SETTING: A specialist organ transplant dermatology clinic. PATIENTS: Twenty-one high-risk patients with skin cancer with comparable areas of clinically atypical skin on dorsal hands or forearms. INTERVENTIONS: Imiquimod or placebo (randomly assigned) applied 3 times a week for 16 weeks to 1 dorsal hand or forearm, with 8 months of follow-up. At week 16, biopsy samples were collected from pre-assigned sites in the treatment and control areas and were examined for dysplasia. MAIN OUTCOME MEASURES: The proportion of patients showing reduced numbers of viral and keratotic lesions and reduced histological severity of dysplasia in the treatment vs control areas at week 16, serum creatinine levels, and tumors developing in the study sites. RESULTS: Fourteen patients receiving imiquimod and 6 receiving placebo completed the study. Seven patients using imiquimod (1 taking placebo) had reduced skin atypia, 7 using imiquimod (none taking placebo) had reduced viral warts, and 5 using imiquimod (1 taking placebo) showed less dysplasia histologically. In 1 year, fewer squamous skin tumors arose in imiquimod-treated skin than in control areas. Renal function was not adversely affected. CONCLUSIONS: Topical 5% imiquimod cream seems to be safe on skin areas up to 60 cm2 in renal transplant recipients. It may be effective in reducing cutaneous dysplasia and the frequency of squamous tumors developing in high-risk patients. Larger studies are required to confirm these results.     

A new comprehensive ultrasonic diagnostic method for celiac artery compression syndrome that hybridizes “arterial compression hook sign” and peak systolic velocity

PurposeDiagnosing celiac artery compression syndrome (CACS) is based on an imaging finding of celiac artery compression (CAC), but the diagnostic criteria are inconsistent. The study aim was to devise an ultrasonographic screening method to effectively diagnose CAC in occult CACS.MethodsThe subjects were 61 patients with suspected CACS who underwent ultrasonography at our hospital from May 2017 to December 2019 and were divided into the following two groups: the “arterial compression hook sign”-positive group (n = 15, mean age: 26.6 ± 16.4 years, six males, nine females) and -negative group (n = 41, mean age: 32.5 ± 18.6 years, 12 males, 34 females). We used B-mode and advanced dynamic flow to detect arterial compression hook sign and pulse Doppler to measure expiration peak systolic velocity (EPSV) and inspiration PSV (IPSV).ResultsThe EPSV was significantly higher in the arterial compression hook sign-positive group (304.7 ± 47.4 cm/s) than in the -negative groups (158.2 ± 38.7 cm/s), (p < 0.001). Receiver operating characteristic curve analysis was performed to calculate the EPSV cutoff value for presence of CAC, which was 226 cm/s (sensitivity: 0.957, specificity: 1.000, AUC: 0.997, 95% confidence interval: 0.99–1). The IPSV was lower in the positive group than in the negative group in all cases (EPSV − IPSV range: 68–199 cm/s).ConclusionOur results showed that if arterial compression hook sign determined by B-mode ultrasound, EPSV > 226 cm/s, and IPSV decreases by ≥ 68 cm/s, then CAC can be detected with high specificity.Graphic abstract      

Association of frequent consumption of fatty fish with prostate cancer risk is modified by COX-2 polymorphism

Dietary intake of marine fatty acids from fish may protect against prostate cancer development. We studied this association and whether it is modified by genetic variation in cyclooxygenase (COX)-2, a key enzyme in fatty acid metabolism and inflammation. We assessed dietary intake of fish among 1,499 incident prostate cancer cases and 1,130 population controls in Sweden. Five single nucleotide polymorphisms (SNPs) were identified and genotyped in available blood samples for 1,378 cases and 782 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression. Multiplicative and additive interactions between fish intake and COX-2 SNPs on prostate cancer risk were evaluated. Eating fatty fish (e.g., salmon-type fish) once or more per week, compared to never, was associated with reduced risk of prostate cancer (OR: 0.57, 95% CI: 0.43-0.76). The OR comparing the highest to the lowest quartile of marine fatty acids intake was 0.70 (95% CI: 0.51-0.97). We found a significant interaction (p < 0.001) between salmon-type fish intake and a SNP in the COX-2 gene (rs5275: +6365 T/C), but not with the 4 other SNPs examined. We found strong inverse associations with increasing intake of salmon-type fish among carriers of the variant allele (OR for once per week or more vs. never = 0.28, 95% CI: 0.18-0.45; p(trend) < 0.01), but no association among carriers of the more common allele. Frequent consumption of fatty fish and marine fatty acids appears to reduce the risk of prostate cancer, and this association is modified by genetic variation in the COX-2 gene.     

People's attitude toward xenotransplantation: affective reactions and the influence of the evaluation context

Abstract: Background: One of the major issues in transplantation is to find a strategy to overcome the scarcity of human organs. One of the interventions under investigation is represented by xenotransplantation. The present study aimed to understand the role of psychological factors on people’s perception of xenotransplantation. In particular, we tested a condition in which different alternatives (e.g., human vs. pig donors) are presented together allowing people to compare among them (joint evaluation) and two conditions in which people are presented with only one of the two alternatives and cannot compare them (separate evaluation). Methods: The study was conducted with three different groups of participants: patients waiting for liver transplantation (N = 31 in joint evaluation and N = 30 in each of the two separate evaluation conditions); students (N = 30 in join evaluation and N = 30 in each of the two separate evaluation conditions); and healthy adults (N = 30 in joint evaluation and N = 30 in each of the two separate evaluation conditions). Participants were presented with hypothetical scenarios and asked how good (or bad) were their feelings toward one or two types of donor (e.g., human and pig). Results: Patients showed a skeptical attitude toward xenotransplantation both when it was evaluated together with the human donor (P < 0.01) or when it was evaluated separately (P < 0.01). Differently, when asked to evaluate each donor separately healthy adults and students showed similar affective reactions toward the two alternatives (human organ and xenograft). Conclusions: The present study demonstrates that the evaluation context may increase the impact of affective reactions and reduce healthy people’s ability to use information on the potential benefit of a novel biomedical technology. Regardless of the evaluation context, patients always rely on affective reactions and show an overall preference for the human organ.