Chimeric calicivirus-like particles elicit protective anti-viral cytotoxic responses without adjuvant

We have analyzed the potential of virus-like particles (VLPs) from rabbit hemorrhagic disease virus (RHDV) as a delivery system for foreign T cell epitopes. To accomplish this goal, we generated chimeric RHDV-VLPs incorporating a CD8⁺ T cell epitope (SIINFEKL) derived from chicken ovalbumin (OVA). The OVA epitope was inserted in the capsid protein (VP60) of RHDV at two different locations: 1) the N-terminus, predicted to be facing to the inner core of the VLPs, and 2) a novel insertion site predicted to be located within an exposed loop. Both constructions correctly assembled into VLPs. In vitro, the chimeric VLPs activated dendritic cells for TNF-α secretion and they were processed and presented to specific T cells. In vivo, mice immunized with the chimeric VLPs without adjuvant were able to induce specific cellular responses mediated by cytotoxic and memory T cells. More importantly, immunization with chimeric VLPs was able to resolve an infection by a recombinant vaccinia virus expressing OVA protein.     

Role of lipopolysaccharide in the induction of type I interferon-dependent cross-priming and IL-10 production in mice by meningococcal outer membrane vesicles

We investigated the contribution of lipopolysaccharide (LPS) to adjuvant properties of native outer membrane vesicles (NOMV), a vaccine candidate for meningococcal B disease. NOMV induce the maturation of and cytokine production by murine bone marrow-derived dendritic cells through both toll-like receptors (TLR) 2 and 4 which are mostly dependent on the signalling adaptor MyD88. NOMV are also able to induce B cell proliferation in splenocytes from LPS-hyporesponsive mice. However, induction of IL-10 and type I interferon-dependent, antigen-specific and IFN_γ-secreting CD8⁺ cytotoxic T lymphocyte responses in vivo by NOMV requires LPS. The importance of LPS in the induction of IL-10 and functional cross-priming has implications for NOMV-based vaccine and adjuvant development.     

Brain injury severity, litigation status, and self-report of postconcussive symptoms

The Postconcussive Symptom Questionnaire (PCSQ) was developed to assess the symptoms associated with the controversial diagnosis of postconcussion syndrome. We examined item endorsement on the PCSQ in two groups. The first group was made up of individuals diagnosed with moderate to severe traumatic brain injury. The second group was made up of individuals meeting criteria for mild traumatic brain injury who exhibited no evidence of neurological injury. In addition, they demonstrated poor effort during neuropsychological examination. Significant differences in item endorsement were found the majority of individual items as well as on the PCSQ indices. The poor effort mild traumatic brain injury group consistently reported more symptoms with greater severity. The results raise further questions about the validity of postconcussion symptoms.     

Expanding the neurologic phenotype of oculodentodigital dysplasia in a 4-generation Hispanic family

We report a 4-generation Hispanic family with oculodentodigital dysplasia whose members were found to have typical phenotypic characteristics of this disorder, as well as a variable expression of neurologic manifestations in multiple generations ranging from a mild spastic gait to moderate to severe spastic tetraparesis/quadriplegia with epilepsy and an abnormal brain and spinal cord magnetic resonance imaging result. Gene testing documented a previously reported missense mutation in GJA1 (connexin 43) exon 2 (c.389T>C;p.I130T). Our evaluation not only expands the phenotypes associated with GJA1 gene mutations but also demonstrates that a great degree of variability in neurological defects can exist within a single family without evidence of genetic anticipation. A genotype-phenotype correlation between the p.I130T mutation and neurologic dysfunction appears more likely with the addition of this report's neurologic and GJA1 gene mutation findings. These findings expand the neurologic phenotype and prognosis and underscore the importance of counseling families with oculodentodigital dysplasia about the possibility of neurologic involvement.     

Treating disseminated fusariosis: amphotericin B,voriconazole or both?

Disseminated Fusarium infection can cause significant morbidity and mortality in immunocompromised patients. We present a case of disseminated fusariosis in a patient with neutropenic fever successfully treated using both liposomal amphotericin B and voriconazole. Combination anti-fungal therapy may be considered for such patients, particularly for those failing single-drug therapy.     

Benefit of a hospital course about organ donation and transplantation: an evaluation by Spanish hospital transplant personnel

A considerable percentage of hospital personnel are against organ donation, which at a crucial time could act as an obstacle to donation. Moreover, there is often a lack of training of personnel necessary for them to provide accurate information about organ donation and transplantation. Our objective was to determine the acceptability of a training course about organ donation among hospital workers in a center with an ongoing solid organ transplant program. MATERIALS AND METHODS: A random sample (n = 1168) was stratified by type of service and job category among workers in hospital services within an organ transplant program. An evaluation was made of attitudes toward donation and acceptance of a training course using a validated psychosocial questionnaire. Distribution of the survey was made by the head of each service and job category. The survey was completed anonymously and self-administered. RESULTS: Sixty-nine percent (n = 808) of respondents were in favor of donating their own organs. With respect to the benefit of a training course about organ donation and transplantation, 50% (n = 584) of respondents considered it to be a useful idea, whereas 15% (n = 176) did not, and 35% (n = 408) were not sure. An important finding was that 56% (n = 452) of those who are in favor of donation would take part in the course compared to only 37% (n = 132) of those who were against or undecided. There was a significant relationship between those workers who believed that the training course will be of use and the following factors: younger age (P = .000); women (P = .000); single (P = .000); nursing job category (P = .000); a temporary contract (P = .012); a worker in nonsurgical services (P = .000); prior understanding of the concept of brain death (P = .003); favoring cadaveric organ donation (P = .000); performing pro-social voluntary type activities (P = .000); discussions of organ donation and transplantation within the family (P = .022); Catholic religion (P = .001); a partner in favor of organ donation and transplantation (P = .001); and a belief that he may need a transplant (P = .000). CONCLUSIONS: A training course about organ donation and transplantation might be useful given that only half of the workers would be prepared to take part and with respect to the target population, only 37% of them stating that they would participate. Its main use would be to reinforce the positive attitude of those who are already in favor and increase their knowledge about the subject. What is more, if these workers received adequate training they would serve to promote donation both directly and indirectly to the general public and other hospital personnel.     

Hospital personnel in surgical services in a transplant hospital faced with living liver donation: an attitudinal survey

Living liver donation is becoming a more widely accepted practice given the decrease in donor morbidity and mortality and the beneficial results in the recipient. Use of this technique is unusual in Spain. There are a number of workers against its use within the health care system. The objective of this study was to analyze attitudes toward and the variables that affect them concerning living liver donation among surgical services in a transplant hospital. MATERIALS AND METHODS: A random survey was stratified by surgical area and job category in a Spanish third-level hospital with an ongoing solid organ transplant program. Attitudes toward living liver donation were assessed using a questionnaire about organ donation and transplantation that evaluated various psychosocial variables. Student's t test and the chi square test were used. RESULTS: A total of 263 workers were surveyed (mean age as 40 +/- 9 years). Regarding attitudes toward living liver donation, the level of acceptance was 80% (n = 211) of respondents, whereas 10% were undecided (n = 26), and another 10% were against (n = 26), assuming that the donations were related. When we asked about unrelated living donation, the percentage in favor decreased to 10% (n = 27). No differences were found with respect to job category or type of service. The variables that are related to such an attitude are the following: (1) possibility of respondent needing an organ (P = .001); (2) favorable attitude toward living kidney donation (P < .000); and (3) a belief that medical errors exist (P = .004). An important finding was that attitudes toward living liver donation were not more favorable according to whether the respondent was in favor or against cadaveric organ donation (P = .175). CONCLUSION: There was a highly favorable attitude toward living liver donation among hospital personnel in surgical services, which is an important factor to take into account if this type of donation is to be encouraged in Spain.