Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation.

Rationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objectives: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

Existence and importance of Na+K+-ATPase in the plasma membrane of boar spermatozoa.

Sodium-potassium-ATPase (Na+K+-ATPase), a target to treat congestive heart failure, is the only known receptor for cardiac glycosides implicated in intracellular signaling and additionally functions enzymatically in ion transport. Spermatozoa need transmembrane ion transport and signaling to fertilize, and Na+K+-ATPase is identified here for the first time in boar spermatozoa. Head plasma membrane (HPM) isolated from boar spermatozoa was confirmed pure by marker enzymes acid and alkaline phosphatase (218 ± 23% and 245 ± 38% enrichment, respectively, versus whole spermatozoa). Western immunoblotting detected α and ß subunits (isoforms α1, α3, ß1, ß2, and ß3) in different concentrations in whole spermatozoa and HPM. Immunofluorescence of intact sperm only detected α3 on the post-equatorial exterior membrane; methanol-permeabilized sperm also had α3 post-equatorially and other isoforms on the acrosomal ridge and cap. Mass spectrometry confirmed the presence of all isoforms in HPM. Incubating boar sperm in capacitating media to induce the physiological changes preceding fertilization significantly increased the percentage of capacitated sperm compared to 0 h control (33.0 ± 2.6% vs. 19.2 ± 2.6% capacitated sperm, respectively; p = 0.014) and altered the ß2 immunofluorescence pattern. These results demonstrate the presence of Na+K+-ATPase in boar sperm HPM and that it changes during capacitation.

A Bright Light at the End of the Tunnel: Factors Associated With Complete Mental Health After a Suicide Attempt.

OBJECTIVE: The aim of this study was to investigate factors associated with complete mental health (CMH) among a nationally representative sample of Canadians who had a history of suicide attempts. METHODS: Data for this study came from the 2012 Canadian Community Health Survey-Mental Health. A subsample of 796 respondents who had ever attempted suicide was analyzed. The outcome variable investigated was CMH, which includes three elements: (a) absence of past-year suicidality or mental illness (measured by the World Health Organization version of the Composite International Diagnostic Interview); (b) happiness or satisfaction; and (c) social and psychological well-being. Bivariate analyses and binary logistic regression were conducted to identify factors associated with CMH among Canadians who had a history of suicide attempts. RESULTS: Of the 796 respondents who had a history of suicide attempts, 28.4% were in CMH. In accordance with past research, positive factors associated with CMH were as follows: having a confidant, lacking chronic pain, absence of insomnia, being female, older age, higher income, and having no history of mental illness, including bipolar disorder, major depressive episode, or generalized anxiety disorder. Those with two suicide attempts were less likely to experience CMH than those with one suicide attempt. Surprisingly, medical attention after the attempt was positively associated with CMH. In total, these factors accounted for 29% of the variance in CMH. CONCLUSIONS: Adults with a history of suicide attempts can achieve an excellent level of mental health. These findings suggest that interventions to promote social support and manage chronic pain and insomnia may be helpful. HIGHLIGHTSMore than one in four adults with a history of suicide attempts are in complete mental healthHaving a confidant was positively associated with having complete mental health after suicide attemptThose with a history of suicide attempts need ongoing mental health support.

Pitfalls and Unexpected Benefits of an Electronic Hand Hygiene Monitoring System.

BACKGROUND: No single strategy is more effective than proper hand hygiene (HH) in reducing the spread of nosocomial infections. Unfortunately, health care worker compliance with HH is imperfect. We sought to improve HH compliance using an electronic hand hygiene monitoring system (EHHMS) in 2 units to collect unbiased data and provide feedback. METHODS: In this prospective, quasi-experimental study, the Hyginex EHHMS was installed in 2 units at Tufts Medical Center. Ninety-one bracelets were assigned, and electronic data were collected over 8 months. Human observations continued. We compared HH compliance as measured by human observation before, during, and after EHHMS implementation. Pre- and post-implementation surveys were distributed to staff. RESULTS: The number of electronically captured HH compliance observations was small due to infrequent bracelet use after month 2 of the intervention. HH compliance, as determined by human observation, increased by an average of 1.3 percentage points per month (P = .0005). Survey responses revealed negative attitudes about the EHHMS before and after its implementation. CONCLUSIONS: Despite poor EHHMS participation and negative attitudes toward its implementation, HH compliance, as measured by human observation, significantly improved. Hospitals considering implementing an EHHMS should look to refine the intervention to encourage health care worker participation.

Racial differences in the development of de-novo donor-specific antibodies and treated antibody-mediated rejection after heart transplantation.

BACKGROUND: Despite improvements in outcomes after heart transplantation, black recipients have worse survival compared with non-black recipients. The source of such disparate outcomes remains largely unknown. We hypothesize that a propensity to generate de-novo donor-specific antibodies (dnDSA) and subsequent antibody-mediated rejection (AMR) may account for racial differences in sub-optimal outcomes after heart transplant. In this study we aimed to determine the role of dnDSA and AMR in racial disparities in post-transplant outcomes. METHODS: This study was a single-center, retrospective analysis of 137 heart transplant recipients (81% male, 48% black) discharged from Emory University Hospital. Patients were classified as black vs non-black for the purpose of our analysis. Kaplan-Meier and Cox regression analyses were used to evaluate the association between race and selected outcomes. The primary outcome was the development of dnDSA. Secondary outcomes included treated AMR and a composite of all-cause graft dysfunction or death. RESULTS: After 3.7 years of follow-up, 39 (28.5%) patients developed dnDSA and 19 (13.8%) were treated for AMR. In multivariable models, black race was associated with a higher risk of developing dnDSA (hazard ratio [HR] 3.65, 95% confidence interval [CI] 1.54 to 8.65, p = 0.003) and a higher risk of treated AMR (HR 4.86, 95% CI 1.26 to 18.72, p = 0.021) compared with non-black race. Black race was also associated with a higher risk of all-cause graft dysfunction or death in univariate analyses (HR 2.10, 95% CI 1.02 to 4.30, p = 0.044). However, in a multivariable model incorporating dnDSA, black race was no longer a significant risk factor. Only dnDSA development was significantly associated with all-cause graft dysfunction or death (HR 4.85, 95% CI 1.89 to 12.44, p = 0.001). CONCLUSION: Black transplant recipients are at higher risk for the development of dnDSA and treated AMR, which may account for racial disparities in outcomes after heart transplantation.