Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys.

The earliest events following mucosal HIV-1 infection, prior to measurable viremia, remain poorly understood. Here, by detailed necropsy studies, we show that the virus can rapidly disseminate following mucosal SIV infection of rhesus monkeys and trigger components of the inflammasome, both at the site of inoculation and at early sites of distal virus spread. By 24 hr following inoculation, a proinflammatory signature that lacked antiviral restriction factors was observed in viral RNA-positive tissues. The early innate response included expression of NLRX1, which inhibits antiviral responses, and activation of the TGF-ß pathway, which negatively regulates adaptive immune responses. These data suggest a model in which the virus triggers specific host mechanisms that suppress the generation of antiviral innate and adaptive immune responses in the first few days of infection, thus facilitating its own replication. These findings have important implications for the development of vaccines and other strategies to prevent infection.

Characterization of CD8+ T cell differentiation following SIVΔnef vaccination by transcription factor expression profiling.

The onset of protective immunity against pathogenic SIV challenge in SIVΔnef-vaccinated macaques is delayed for 15-20 weeks, a process that is related to qualitative changes in CD8+ T cell responses induced by SIVΔnef. As a novel approach to characterize cell differentiation following vaccination, we used multi-target qPCR to measure transcription factor expression in naïve and memory subsets of CD8++ T cells, and in SIV-specific CD8+ T cells obtained from SIVΔnef-vaccinated or wild type SIVmac239-infected macaques. Unsupervised clustering of expression profiles organized naïve and memory CD8+ T cells into groups concordant with cell surface phenotype. Transcription factor expression patterns in SIV-specific CD8+ T cells in SIVΔnef-vaccinated animals were distinct from those observed in purified CD8+ T cell subsets obtained from naïve animals, and were intermediate to expression profiles of purified central memory and effector memory T cells. Expression of transcription factors elicited by SIVΔnef vaccination also varied over time: cells obtained at later time points, temporally associated with greater protection, appeared more central-memory like than cells obtained at earlier time points, which appeared more effector memory-like. Expression of transcription factors associated with effector differentiation, such as ID2 and RUNX3, were decreased over time, while expression of transcription factors associated with quiescence or memory differentiation, such as TCF7, BCOR and EOMES, increased. CD8+ T cells specific for a more conserved epitope expressed higher levels of TBX21 and BATF, and appeared more effector-like than cells specific for an escaped epitope, consistent with continued activation by replicating vaccine virus. These data suggest transcription factor expression profiling is a novel method that can provide additional data complementary to the analysis of memory cell differentiation based on classical phenotypic markers. Additionally, these data support the hypothesis that ongoing stimulation by SIVΔnef promotes a distinct protective balance of CD8+ T cell differentiation and activation states.

Factors influencing the acceptance of toenail-to-fingernail transfer.

The aim of this study is to determine the factors influencing the acceptance of toenail-to-fingernail transfer. A total of 240 patients were divided into four groups according to severity of nail injury. Half (expensed informed [EI] group) were informed about the expenses (about $9,000) before the interview; the other half were not informed (the expense not-informed [ENI] group). The participants were asked to answer yes or no to the question "If you lose your fingernail and it can be reconstructed by transferring your toenail like this figure, will you undergo surgery? If you want it or not, please choose the reason for your choice." In the EI group, 68.3% accepted the surgery. In the ENI group, 85.0% accepted the surgery. There was a significant difference between the EI and ENI groups (p = 0.002). In the EI group, the age of the surgery acceptance group (36.9 ± 11.8) was significantly lower (p = 0.004) than that of the surgery rejection group (44.5 ± 15.5). The young age group wished to accept the surgery irrespective of the expenses, yet the old age group hesitated to have surgery when informed about the expenses. We think the risk acceptance for toenail-to-fingernail transfer mostly depends upon the expense.

Use of a Self-Report Medication Adherence Scale for Measuring Adherence to Antiretroviral Therapy in Patients With HIV/AIDS.

BACKGROUND AND PURPOSE: This study examined the psychometric properties of a 9-item Morisky Medication Adherence Scale (MMAS-9) adapted specifically for patients with HIV/AIDS. METHODS: We used data from two randomized controlled trials investigating telephone-delivered interventions for improving adherence to antiretroviral therapy to assess reliability (Cronbach's α and Pearson's product correlation) and validity (convergent and concurrent) of the MMAS-9. RESULTS: The internal consistency (Cronbach's α) of the MMAS-9 was .66 (study 1) and .69 (study 2); 3-month test-retest reliability (Pearson's correlation) ranged from .50 to .74. Validity was supported by associations with electronic event monitored adherence, social support, depressive symptoms, self-efficacy, stigma, regimen complexity, and impact of side effects in the hypothesized direction. CONCLUSIONS: The adapted MMAS-9 demonstrated good convergent validity but somewhat lower internal consistency reliability than other reports.

Comparison of Dietary Quality Assessment Using Food Frequency Questionnaire and 24-hour-recalls in Older Men and Women.

OBJECTIVES: To examine the agreement in nutrient intake and alternative healthy eating indices (AHEI) between a self-administered Food Frequency Questionnaire (FFQ) and 24-hour recall (24HR) measurements of diet by gender, among older adults. MATERIAL AND METHODS: This is a cross-sectional observational study of 105 men and 99 women aged 65 and older living in urban and rural neighborhoods in Worcester County, Massachusetts, USA. Participants were queried on diet using both FFQ and 24HR. The healthy eating classification was compared between the two instruments by gender. RESULTS: For men, the mean ± SD of AHEI total score was 48.2 ± 12.3 based on FFQ versus 34.7 ± 10.2 based on 24HR. For women, the mean ± SD was 47.9 ± 10.1 based on FFQ versus 36.1 ± 10.0 based on 24HR. Using 32 as the cutoff (40% of maximum AHEI score), 9% of men and 7% of women were classified as eating unhealthy based on the FFQ, versus 47% of men and 38% of women based on 24HR. Compared to women, men had larger 24HR to FFQ discrepancies in the nuts and vegetable protein subscore and white/red meat ratio, and smaller discrepancy in alcohol beverages subscore. CONCLUSION: Agreements between FFQ and 24HR-based measures of diet quality were roughly comparable between men and women, though slightly better for women than men. Compared to 24HR, the FFQ tended to underestimate the proportions of older men and women classified as eating unhealthy and misclassified more men than women. Such limitations should be considered when the FFQ is used to study healthy eating in older age.

Gray's time-varying coefficients model for posttransplant survival of pediatric liver transplant recipients with a diagnosis of cancer.

Transplantation is often the only viable treatment for pediatric patients with end-stage liver disease. Making well-informed decisions on when to proceed with transplantation requires accurate predictors of transplant survival. The standard Cox proportional hazards (PH) model assumes that covariate effects are time-invariant on right-censored failure time; however, this assumption may not always hold. Gray's piecewise constant time-varying coefficients (PC-TVC) model offers greater flexibility to capture the temporal changes of covariate effects without losing the mathematical simplicity of Cox PH model. In the present work, we examined the Cox PH and Gray PC-TVC models on the posttransplant survival analysis of 288 pediatric liver transplant patients diagnosed with cancer. We obtained potential predictors through univariable (P < 0.15) and multivariable models with forward selection (P < 0.05) for the Cox PH and Gray PC-TVC models, which coincide. While the Cox PH model provided reasonable average results in estimating covariate effects on posttransplant survival, the Gray model using piecewise constant penalized splines showed more details of how those effects change over time.

Flexor tenorrhaphy using absorbable suture materials.

BACKGROUND: Nonabsorbable sutures are favorable for repairing flexor tendons. However, absorbable sutures have performed favorably in an animal model. METHODS: Two-strand sutures using the interlocking modified Kessler method with polydioxanone absorbable sutures 4-0 were used to repair completely ruptured flexor tendons in 55 fingers from 41 consecutive patients. The medical records of average 42 follow up weeks were analyzed retrospectively. The data analyzed using the chi-squared test, and Fisher's exact test was used for postoperative complications. The results were compared with those of other studies. RESULTS: Among the index, middle, ring, and little fingers were injured in 9, 17, 16, and 13 fingers, respectively. The injury levels varied from zone 1 to 5. Of the 55 digits in our study, there were 26 (47%) isolated flexor digitorum profundus (FDP) injuries and 29 (53%) combined FDP and with flexor digitorum superficialis injuries. Pulley repair was also conducted. Concomitant injuries of blood vessels and nerves were found in 17 patients (23 fingers); nerve injuries occurred in 5 patients (10 fingers). Two patients had ruptures (3.6%), and one patient had two adhesions (3.6%). Using the original Strickland criteria, all the patients were assessed to be excellent or good. Also, fibrosis and long-term foreign body tissue reactions such as stitch granuloma were less likely occurred in our study. Compared to the Cullen's report that used nonabsorbable sutures, there was no significant difference in the rupture or adhesion rates. CONCLUSIONS: Therefore, this study suggests that appropriate absorbable core sutures can be used safely for flexor tendon repairs.