Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo

To develop more effective vaccines and strategies to regulate chronic inflammatory diseases, it is important to understand the mechanisms of immunological memory. Factors regulating memory CD4⁺ T helper (Th)-cell pool size and function remain unclear, however. We show that activation of type I invariant natural killer T (iNKT) cells with glycolipid ligands and activation of type II natural killer T (NKT) cells with the endogenous ligand sulfatide induced dramatic proliferation and expansion of memory, but not naïve, CD4 T cells. NKT cell-induced proliferation of memory Th1 and Th2 cells was dependent largely on the production of IL-2, with Th2-cell proliferation also affected by loss of IL-4. Type II NKT cells were also required for efficient maintenance of memory CD4 T cells in vivo. Activation of iNKT cells resulted in up-regulation of IFN-γ expression by memory Th2 cells. These IFN-γ–producing memory Th2 cells showed a decreased capability to induce Th2 cytokines and eosinophilic airway inflammation. Thus, activated NKT cells directly regulate memory CD4 T-cell pool size and function via the production of cytokines in vivo.     

Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909

Background

In the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial.

Design and Methods

Peripheral blood and bone marrow samples were collected during different phases of the Cancer and Leukemia Group B 59909 study for minimal residual disease analysis. Minimal residual disease status was determined by quantitative polymerase chain reaction of IgH and/or BCL-1/JH gene rearrangement. Correlation of minimal residual disease status with time to progression and overall survival was determined. In multivariable analysis, minimal residual disease, and other risk factors were correlated with time to progression.

Results

Thirty-nine patients had evaluable, sequential peripheral blood and bone marrow samples for minimal residual disease analysis. Using peripheral blood monitoring, 18 of 39 (46%) achieved molecular remission following induction therapy. The molecular remission rate increased from 46 to 74% after one course of intensification therapy. Twelve of 21 minimal residual disease positive patients (57%) progressed within three years of follow up compared to 4 of 18 (22%) molecular remission patients (P=0.049). Detection of minimal residual disease following induction therapy predicted disease progression with a hazard ratio of 3.7 (P=0.016). The 3-year probability of time to progression among those who were in molecular remission after induction chemotherapy was 82% compared to 48% in patients with detectable minimal residual disease. The prediction of time to progression by post-induction minimal residual disease was independent of other prognostic factors in multivariable analysis.

Conclusions

Detection of minimal residual disease following induction immunochemotherapy was an independent predictor of time to progression following immunochemotherapy and autologous stem cell transplantation for mantle cell lymphoma. The clinical trial was registered at ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00020943","term_id":"NCT00020943"}}NCT00020943.     

Surgical suture assembled with polymeric drug-delivery sheet for sustained,local pain relief

Surgical suture is a strand of biocompatible material designed for wound closure, and therefore can be a medical device potentially suitable for local drug delivery to treat pain at the surgical site. However, the preparation methods previously introduced for drug-delivery sutures adversely influenced the mechanical strength of the suture itself – strength that is essential for successful wound closure. Thus, it is not easy to control drug delivery with sutures, and the drug-delivery surgical sutures available for clinical use are now limited to anti-infection roles. Here, we demonstrate a surgical suture enabled to provide controlled delivery of a pain-relief drug and, more importantly, we demonstrate how it can be fabricated to maintain the mechanical strength of the suture itself. For this purpose, we separately prepare a drug-delivery sheet composed of a biocompatible polymer and a pain-relief drug, which is then physically assembled with a type of surgical suture that is already in clinical use. In this way, the drug release profiles can be tailored for the period of therapeutic need by modifying only the drug-loaded polymer sheet without adversely influencing the mechanical strength of the suture. The drug-delivery sutures in this work can effectively relieve the pain at the surgical site in a sustained manner during the period of wound healing, while showing biocompatibility and mechanical properties comparable to those of the original surgical suture in clinical use.     

Factors associated with past research participation among low-income persons living with HIV

We described influences on past research participation among low-income persons living with HIV (PLWH) and examined whether such influences differed by study type. We analyzed a convenience sample of individuals from a large, urban clinic specializing in treating low-income PLWH. Using a computer-assisted survey, we elicited perceptions of research and participating in research, barriers, benefits, "trigger" influences, and self-efficacy in participating in research. Of 193 participants, we excluded 14 who did not identify any type of study participation, and 17 who identified "other" as study type, resulting in 162 cases for analysis. We compared results among four groups (i.e., 6 comparisons): past medical participants (n=36, 22%), past behavioral participants (n=49, 30%), individuals with no past research participation (n=52, 32%), and persons who had participated in both medical and behavioral studies (n=25, 15%). Data were analyzed using chi-square tests for categorical variables and ANOVA for continuous variables. We employed a multinomial probit (MNP) model to examine the association of multiple factors with the outcome. Confidence in ability to keep appointments, and worry about being a 'guinea pig' showed statistical differences in bivariate analyses. The MNP regression analysis showed differences between and across all 6 comparison groups. Fewer differences were seen across groupings of medical participants, behavioral participants, and those with no past research experience, than in comparisons with the medical-behavioral group. In the MNP regression model 'age' and level of certainty regarding 'keeping yourself from being a guinea pig' showed significant differences between past medical participants and past behavioral participants.     

A geopolymer route to micro- and meso-porous carbon

Hexagonal and wormhole-type mesoporous geopolymers were developed by controlling the concentration of a structure directing agent (cetrimonium bromide, CTAB) with fixed ratios of Si/Al, KOH/(Si + Al), and H₂O/(Si + Al), and their detailed porous structures were confirmed by TEM, N₂ adsorption–desorption and X-ray diffraction measurements. The as-prepared geopolymers were then used as templates to replicate porous carbons with various structures and porosities for CO₂ adsorption. To understand the correlation between the CO₂ adsorptivity and porous structures, we tuned the porosity of the geopolymer-templated carbons by modifying the structures of the geopolymers. The porous carbons obtained from the hexagonal-type porous geopolymers were found to be composed of the aggregates of carbon nanowires exhibiting large particles, while those obtained from the wormhole-like porous geopolymers were determined to be wormhole type as well, as evidenced by TEM and X-ray diffraction studies. According to the CO₂ adsorption isotherms of the porous carbons, the aggregates of carbon nanowires exhibited the highest CO₂ adsorptivity due to their highest microporosity and largest specific surface area.

We report the synthesis of microporous carbon through a geopolymer route starting from natural clay kaolinite.     

Exeter Short Stems Compared With Standard Length Exeter Stems : Experience From the Australian Orthopaedic Association National Joint Replacement Registry

The standard Exeter stem has a length of 150 mm with offsets 37.5 to 56 mm. Shorter stems of lengths 95, 115 and 125 mm with offsets 35.5 mm or less are available for patients with smaller femurs. Concern has been raised regarding the behavior of the smaller implants. This paper analyzed data from the Australian Orthopaedic Association National Joint Replacement Registry comparing survivorship of stems of offset 35.5 mm or less with the standard stems of 37.5 mm offset or greater. At 7 years, there was no significant difference in the cumulative percent revision rate in the short stems (3.4%, 95% CI 2.4-4.8%) compared with the standard length stems (3.5%, 95% CI 3.3-3.8%) despite its use in a greater proportion of potentially more difficult developmental dysplasia of the hip cases.     

LCP distal ulna hook plate as alternative fixation for fifth metatarsal base fracture

Intramedullary screw fixation is the most common treatment for fifth metatarsal base fractures. Screw application does not achieve accurate reduction in fracture with small fragments, osteoporotic bone, or Lawrence zone 1 fractures, however. On the basis of similar anatomical architectures between the distal ulna and the fifth metatarsal base, the purpose of this study was to assess the results of a locking compression plate (LCP) distal ulna hook plate in stabilizing displaced zone 1 or 2 fifth metatarsal base fractures. Nineteen patients with Lawrence zone 1 (n = 12) or 2 (n = 7) fractures of the fifth metatarsal base were treated surgically with an LCP distal ulna hook plate. The patients were evaluated clinically and radiographically, and functional outcomes were graded by using the American Orthopaedic Foot and Ankle Society (AOFAS) midfoot scoring system. Radiographic bony union was obtained in all patients, at an average of 7.4 weeks. The mean AOFAS midfoot score improved from 26 (range, 0–45) preoperatively to 94 (range, 72–100) points at the final follow-up. There were three patients with post-traumatic cubometatarsal arthrosis and one patient with sural nerve neuropraxia. In our experience, the distal ulna hook plate achieves a high rate of bony consolidation and anatomically suitable fixation in zone 1 or 2 fifth metatarsal base fractures. We also suggest that the LCP distal ulna hook plate should be considered as an alternative treatment in multifragmentary, osteoporotic, and tuberosity avulsion (zone 1) fifth metatarsal base fractures.