The nature and combination of subunits used in epitope-based Schistosoma japonicum vaccine formulations affect their efficacy

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis remains a major public health problem in endemic countries and is caused by infections with any one of three primary schistosome species. Although there are no vaccines available to date, this strategy appears feasible since natural immunity develops in individuals suffering from repeated infection during a lifetime. Since vaccinations resulting in both Th1- and Th2-type responses have been shown to contribute to protective immunity, a vaccine formulation with the capacity for stimulating multiple arms of the immune response will likely be the most effective. Previously we developed partially protective, single Th- and B cell-epitope-based peptide-DNA dual vaccines (PDDV) (T3-PDDV and B3-PDDV, respectively) capable of eliciting immune responses against the <it>Schistosoma japonicum </it>22.6 kDa tegument antigen (Sj22.6) and a 62 kDa fragment of myosin (Sj62), respectively.</p> <p>Results</p> <p>In this study, we developed PDDV cocktails containing multiple epitopes of <it>S. japonicum </it>from Sj22.6, Sj62 and Sj97 antigens by predicting cytotoxic, helper, and B-cell epitopes, and evaluated vaccine potential <it>in vivo</it>. Results showed that mice immunized with a single-epitope PDDV elicited either Tc, Th, or B cell responses, respectively, and mice immunized with either the T3- or B3- single-epitope PDDV formulation were partially protected against infection. However, mice immunized with a multicomponent (3 PDDV components) formulation elicited variable immune responses that were less immunoprotective than single-epitope PDDV formulations.</p> <p>Conclusions</p> <p>Our data show that combining these different antigens did not result in a more effective vaccine formulation when compared to each component administered individually, and further suggest that immune interference resulting from immunizations with antigenically distinct vaccine targets may be an important consideration in the development of multicomponent vaccine preparations.</p

Dynamics of Th17 Cells and Their Role in Schistosoma japonicum Infection in C57BL/6 Mice

Th17 immune cells secrete the IL-17 cytokine and contribute to host defenses against certain infections. Recent studies linked IL-17 with the severity of liver inflammation and suggested that Th17 cells contribute to the pathology in schistosomiasis, a serious disease caused by parasitic worms such as Schistosoma japonicum widespread in vertebrates including humans. However, the role of Th17 cells in protection against S. japonicum infection is still unclear. For the first time, we describe here the changes in Th17 cell levels during S. japonicum infection and suggest that the schistosome egg antigens are primarily responsible for stimulating the generation of host Th17 cells after S. japonicum infection. We further show that the level of Th17 cells in the host is determined by a combination of factors, namely exposure to complex parasitic antigens that either induce or suppress their generation. We also suggest that lowering IL-17 levels may favor the host's protective responses against S. japonicum infection. Our findings help to better understand the relationship between the host and parasite in terms of immune protection and pathology in schistosomiasis and may contribute to the future development of vaccination and therapeutic strategies

Horrifying Basal Cell Carcinoma Presenting as Progressive Pyoderma Gangrenosum: Case Report

Introduction: Skin ulcers can be challenging to diagnose and manage, particularly with comorbid autoimmune and gastrointestinal diseases. Occam’s razor encourages the simplest explanation to guide care, but reconsideration must occur when intervention proves futile. Case Presentation: We report the case of a 70-year-old male, with a 17-year history of expanding pretibial skin ulcer, presumed by prior care providers to be pyoderma gangrenosum related to Crohn’s disease. A surgical biopsy performed upon presentation to our institution revealed basal cell carcinoma of the skin, invasive to the proximal tibia with associated deep infection, prompting transfemoral amputation. Conclusion: This report is written as a reminder to reconsider a diagnosis and consider seeking additional expertise when a patient’s condition progressively worsens despite intervention. Earlier diagnosis likely would have facilitated therapeutic limb salvage care

Unexpected positive intraoperative cultures (UPIC) at index osseointegration do not lead to increased postoperative infectious events

Introduction: The most common complication following transcutaneous osseointegration for amputees is infection. Although an obvious source of contamination is the permanent stoma, operative site contamination at the time of implantation may be an additional source. This study investigates the impact of unexpected positive intraoperative cultures (UPIC) on postoperative infection. Methods: Charts were reviewed for 8 patients with UPIC and 22 patients with negative intraoperative cultures (NIC) who had at least 1 year of post-osseointegration follow-up. All patients had 24 h of routine postoperative antibiotic prophylaxis, with UPIC receiving additional antibiotics guided by culture results. The main outcome measure was postoperative infection intervention, which was graded as (0) none, (1) antibiotics unrelated to the initial surgery, (2) operative debridement with implant retention, or (3) implant removal. Results: The UPIC vs. NIC rate of infection management was as follows: Grade 0, 6/8 = 75 % vs. 14/22 = 64 %, p = 0.682; Grade 1, 2/8 = 25 % vs. 8/22 = 36.4 % (Fisher's p = 0.682); Grade 2, 1/8 = 12.5 % vs. 0/22 = 0 % (Fisher's p = 0.267); Grade 3, 0/8 = 0 % vs. 1/22 = 4.5 % (Fisher's p = 1.000). No differences were statistically significant. Conclusions: UPIC at index osseointegration, managed with directed postoperative antibiotics, does not appear to increase the risk of additional infection management. The therapeutic benefit of providing additional directed antibiotics versus no additional antibiotics following UPIC is unknown and did not appear to increase the risk of other adverse outcomes in our cohort.</p

International survey on the management of esophageal atresia

IntroductionBecause many aspects of the management of esophageal atresia (EA) are still controversial, we evaluated the practice patterns of this condition across Europe. MethodsA survey was completed by 178 delegates (from 45 [27 European] countries; 88% senior respondents) at the EUPSA-BAPS 2012. ResultsApproximately 66% of respondents work in centers where more than five EA repairs are performed per year. Preoperatively, 81% of respondents request an echocardiogram, and only 43% of respondents routinely perform preoperative bronchoscopy. Approximately 94% of respondents prefer an open approach, which is extrapleural in 71% of respondents. There were no differences in use of thoracoscopy between Europeans (10%) and non-Europeans (11%, p=nonsignificant). Approximately 60% of respondents measure the gap intraoperatively. A transanastomotic tube (90%) and chest drain (69%) are left in situ. Elective paralysis is adopted by 56% of respondents mainly for anastomosis tension (65%). About 72% of respondents routinely request a contrast study on postoperative day 7 (2-14). Approximately 54% of respondents use parenteral nutrition, 40% of respondents start transanastomotic feeds on postoperative day 1, and 89% of respondents start oral feeds after postoperative day 5. Pure EA: 46% of respondents work in centers that repair two or more than two pure EA a year. About 60% of respondents opt for delayed primary anastomosis at 3 months (1-12 months) with gastrostomy formation without esophagostomy. Anastomosis is achieved with open approach by 85% of respondents. About 47% of respondents attempt elongation of esophageal ends via Foker technique (43%) or with serial dilations with bougies (41%). Approximately 67% of respondents always attempt an anastomosis. Gastric interposition is the commonest esophageal substitution. ConclusionMany aspects of EA management are lacking consensus. Minimally invasive repair is still sporadic. We recommend establishment of an EA registry

Quasiparticle Inelastic Lifetime from Paramagnons in Disordered Superconductors

The paramagnon contribution to the quasiparticle inelastic scattering rate in disordered superconductors is presented. Using Anderson's exact eigenstate formalism, it is shown that the scattering rate is Stoner enhanced and is further enhanced by the disorder relative to the clean case in a manner similar to the disorder enhancement of the long-range Coulomb contribution. The results are discussed in connection with the possibility of conventional or unconventional superconductivity in the borocarbides. The results are compared to recent tunneling experiments on LuNi$_{2}$B$_{2}$C.Comment: 5 pages, no figure

A study of the superconducting gap in RNi2_2B2_2C (R = Y, Lu) single crystals by inelastic light scattering

Superconductivity-induced changes in the electronic Raman scattering response were observed for the RNi$_2$B$_2$C (R = Y, Lu) system in different scattering geometries. In the superconducting state, 2$\Delta$-like peaks were observed in A$_{1g}$, B$_{1g}$, and B$_{2g}$ spectra from single crystals. The peaks in A$_{1g}$ and B$_{2g}$ symmetries are significantly sharper and stronger than the peak in B$_{1g}$ symmetry. The temperature dependence of the frequencies of the 2$\Delta$-like peaks shows typical BCS-type behavior, but the apparent values of the $2\Delta$ gap are strongly anisotropic for both systems. In addition, for both YNi$_2$B$_2$C and LuNi$_2$B$_2$C systems, there exists reproducible scattering strength below the $2\Delta$ gap which is roughly linear to the frequency in B$_{1g}$ and B$_{2g}$ symmetries. This discovery of scattering below the gap in non-magnetic borocarbide superconductors, which are thought to be conventional BCS-type superconductors, is a challenge for current understanding of superconductivity in this system.Comment: Added text, changed a figure, and added references. Will appear in Phys. Rev.

Periprosthetic osseointegration fractures are infrequent and management is familiar

Aims Osseointegrated prosthetic limbs allow better mobility than socket-mounted prosthetics for lower limb amputees. Fractures, however, can occur in the residual limb, but they have rarely been reported. Approximately 2% to 3% of amputees with socket-mounted prostheses may fracture within five years. This is the first study which directly addresses the risks and management of periprosthetic osseointegration fractures in amputees. Methods A retrospective review identified 518 osseointegration procedures which were undertaken in 458 patients between 2010 and 2018 for whom complete medical records were available. Potential risk factors including time since amputation, age at osseointegration, bone density, weight, uni/bilateral implantation and sex were evaluated with multiple logistic regression. The mechanism of injury, technique and implant that was used for fixation of the fracture, pre-osseointegration and post fracture mobility (assessed using the K-level) and the time that the prosthesis was worn for in hours/day were also assessed. Results There were 22 periprosthetic fractures; they occurred exclusively in the femur: Two in the femoral neck, 14 intertrochanteric and six subtrochanteric, representing 4.2% of 518 osseointegration operations and 6.3% of 347 femoral implants. The vast majority (19/22, 86.4%) occurred within 2 cm of the proximal tip of the implant and after a fall. No fractures occurred spontaneously. Fixation most commonly involved dynamic hip screws (10) and reconstruction plates (9). No osseointegration implants required removal, the K-level was not reduced after fixation of the fracture in any patient, and all retained a K-level of = 2. All fractures united, 21 out of 22 patients (95.5%) wear their osseointegration-mounted prosthetic limb longer daily than when using a socket, with 18 out of 22 (81.8%) reporting using it for = 16 hours daily. Regression analysis identified a 3.89-fold increased risk of fracture for females (p = 0.007) and a 1.02-fold increased risk of fracture per kg above a mean of 80.4 kg (p = 0.046). No increased risk was identified for bilateral implants (p = 0.083), time from amputation to osseointegration (p = 0.974), age at osseointegration (p = 0.331), or bone density (g/cm2, p = 0.560; T-score, p = 0.247; Z-score, p = 0.312). Conclusion The risks and sequelae of periprosthetic fracture after press-fit osseointegration for amputation should not deter patients or clinicians from considering this procedure. Females and heavier patients are likely to have an increased risk of fracture. Age, years since amputation, and bone density do not appear influential