An investigation of the role of estradiol in fear reduction during a single session of exposure therapy.

Research suggests that estradiol may moderate fear extinction. It is unclear whether these results generalize to exposure therapy. The aim of the current study was to determine whether estradiol moderates outcomes in exposure therapy among women with anxiety disorders. Participants were 35 women with a primary diagnosis of an anxiety disorder who participated in the study as part of routine care at an anxiety specialty clinic. Endogenous estradiol was assessed via saliva. They provided subjective distress ratings before (pre) and after (post) an exposure session, as well as after a brief delay (recall). Contrary to predictions, there were no significant differences in exposure outcomes between the high and low estradiol groups. However, among participants with primary obsessive-compulsive disorder (OCD), results were partially consistent with the hypotheses. Women with lower estradiol initially demonstrated more improvement in subjective distress from pre- to post-exposure, but after the delay, significantly greater distress (attenuated extinction recall). Results suggest that women with lower estradiol may respond less favorably to exposure therapy for OCD relative to women with higher estradiol. These findings await replication in larger samples with longer recall delays. Should replication occur, these results may inform the use of estradiol to augment exposure therapy.

An Investigation of the Moderating Role of Estradiol in Interoceptive Exposure Therapy for Women with Panic Disorder.

Emerging research in animal models and healthy women indicates that the sex hormone estradiol may moderate fear of extinction. There is limited research on estradiol in exposure-based therapy among clinically anxious women. The current pilot study aimed to address this gap by comparing exposure outcomes in women with panic disorder (PD) who had high (HE) vs. low estradiol (LE). Twenty-eight women (14 per group) with PD completed two interoceptive exposure sessions on consecutive days as well as self-report measures of panic severity. Electrodermal activity was assessed continuously throughout the exposure sessions. Results showed that although anxiety sensitivity and subjective distress improved from pre- to postexposure, suggesting that the intervention was effective in reducing panic-related anxiety, there were no differences in outcomes between the HE and LE groups. The findings suggest that estradiol may not moderate outcomes in exposure therapy in clinically anxious samples, although replication in larger samples will be needed.

Evaluation of Metallo-ß-Lactamase Susceptibility Testing in a Physiologic Medium.

Research in identifying alternative growth media that better mimic host conditions is gaining ground. Relative to nutrient-rich Mueller-Hinton broth (MHB), data on the influence of physiologic or host-mimicking media on metallo-ß-lactamase (MBL) resistance are lacking. The objective was to evaluate meropenem susceptibility against clinical and engineered MBL-harboring Enterobacterales strains in a physiologic medium (urine). Antimicrobial susceptibility testing (AST) by broth microdilution was conducted with a wild-type Klebsiella pneumoniae strain and two engineered isogenic variants harboring K. pneumoniae carbapenemase 2 (KPC-2) or New Delhi MBL 1 (NDM-1), as well as two clinical K. pneumoniae isolates (harboring NDM-1 and VIM-1). MICs were determined in conventional cation-adjusted MHB (caMHB) and sterile-filtered urine samples (18 patients). All KPC- and MBL-harboring isolates were meropenem resistant (MICs of ≥16 mg/liter) in caMHB. AST of the KPC isolate in urine resulted in 50% (9/18 urine samples) essential agreement (i.e., within ±1 dilution, relative to the caMHB MIC), highlighting challenges with the use of urine as a medium capable of supporting AST. In the 9 AST-viable urine samples, meropenem MICs were 2- to 9-fold lower than that in caMHB (MIC of 32 mg/liter) among MBL-harboring isolates. Zinc concentrations determined by inductively coupled plasma mass spectrometry averaged 1.25 mg/liter and ranged from 0.12 to 1.14 mg/liter in caMHB and 18 urine samples, respectively. The full extent of MBL-mediated resistance among K. pneumoniae isolates appears to be attenuated in urine. Factors influencing free bioactive zinc levels warrant further investigation. IMPORTANCE Studies assessing antibiotic susceptibility profiles in nonconventional media are lacking. MBL-mediated resistance has come under scrutiny due to the dependence on extracellular zinc concentrations, which makes the choice of testing medium influential for ß-lactam MICs. This study explores human urine as a physiologically relevant matrix with which susceptibility profiles of MBL-harboring isolates can be assessed, relative to conventional broth.

Low Estradiol May Not Impede Cognitive Restructuring in Women With Anxiety Disorders.

Prior research suggests that estradiol may moderate fear extinction in animal models and humans. Based on these findings, estradiol may also moderate cognitive reappraisal, which is theorized to be an important mechanism of change in extinction-based therapy (exposure therapy). We compared cognitive restructuring (CR) skills acquisition and outcome between women with primary anxiety disorders who had high versus low estradiol using a standardized CR task that closely resembles clinical practice. As a proxy of CR outcome, we assessed subjective distress ratings before and after the task and psychophysiological arousal (heart rate and electrodermal activity) throughout the task. Contrary to predictions, results showed that CR skills acquisition and outcome did not differ between the high and low estradiol groups. Although both groups demonstrated reductions in negative affect and skin conductance responses during the CR task, suggesting that participants were able to acquire CR skills and use them effectively to regulate distress, the groups did not differ with respect to CR ability or outcome. The findings suggest that estradiol may not moderate cognitive reappraisal, and may have more of an effect on basic habituation and extinction processes instead.

Significance of Best Spirometry in the First Year After Bilateral Lung Transplantation: Association With 3-Year Outcomes.

BACKGROUND: Spirometry is the cornerstone of monitoring allograft function after lung transplantation (LT). We sought to determine the association of variables on best spirometry during the first year after bilateral LT with 3-year posttransplant survival. METHODS: We reviewed charts of patients who survived at least 3 months after bilateral LT (n = 157; age ± SD: 54 ± 13 y, male:female = 91:66). Best spirometry was calculated as the average of 2 highest measurements at least 3 weeks apart during the first year. Airway obstruction was defined as forced expiratory volume in 1-second (FEV1)/forced vital capacity (FVC) ratio <0.7. Survival was compared based on the ventilatory defect and among groups based on the best FEV1 and FVC measurements (>80%, 60%-80%, and <60% predicted). Primary outcome was 3-year survival. RESULTS: Overall, 3-year survival was 67% (n = 106). Obstructive defect was uncommon (7%) and did not have an association with 3-year survival (72% versus 67%, P = 0.7). Although one-half patients achieved an FVC>80% predicted (49%), 1 in 5 (19%) remained below 60% predicted. Irrespective of the type of ventilatory defect, survival worsened as the best FVC (% predicted) got lower (>80: 80.8%; 60-80: 63.3%; <60: 40%; P < 0.001). On multivariate logistic regression analysis, after adjusting for age, gender, transplant indication, and annual bronchoscopy findings, best FVC (% predicted) during the first year after LT was independently associated with 3-year survival. CONCLUSIONS: A significant proportion of bilateral LT patients do not achieve FVC>80% predicted. Although the type of ventilatory defect on best spirometry does not predict survival, failure to achieve FVC>80% predicted during the first year was independently associated with 3-year mortality.

Why Are Queens Broodless? Failed Nest Initiation Not Linked to Parasites, Mating Status, or Ovary Development in Two Bumble Bee Species of Pyrobombus (Hymenoptera: Apidae: Bombus).

Bumble bees (Bombus [Hymenoptera: Apidae]) are important pollinators for agricultural crops, which has led to their commercial domestication. Despite their importance, little is known about the reproductive biology of bumble bees native to North America. The Hunt bumble bee (Bombus huntii Greene [Hymenoptera: Apidae]) and the Vosnesensky bumble bee (Bombus vosnesenskii Radoszkowski [Hymenoptera: Apidae] are native candidates for commercial production in western North America due to their efficacy in providing commercial pollination services. Availability of pollinators native to the region in which services would be provided would minimize the likelihood of introducing exotic species and spreading novel disease. Some parasites are known to affect bumble bee reproduction, but little is known about their prevalence in North America or how they affect queen success. Only 38% of wild-caught B. huntii and 51% wild-caught B. vosnesenskii queens collected between 2015 and 2017 initiated nests in the laboratory. Our objective was to identify causal factors leading to a queen's inability to oviposit. To address this, we dissected each broodless queen and diagnosed diseases, assessed mating status, and characterized ovary development. Nematodes, arthropods, and microorganisms were detected in both species. Overall, 20% of queens were infected by parasites, with higher rates in B. vosnesenskii. Over 95% of both species were mated, and over 88% had developed ovaries. This suggests that parasitism and mating status were not primary causes of broodlessness. Although some failure to nest can be attributed to assessed factors, additional research is needed to fully understand the challenges presented by captive rearing.

Incidence and variables associated with 30-day mortality after lung transplantation.

BACKGROUND: With the introduction of the lung allocation score (LAS), sicker patients are prioritized for lung transplantation (LT). There is a lack of data regarding variables independently associated with 30-day mortality after LT. METHODS: We queried the UNOS database for adult patients undergoing LT between 1989 and 2014. Patients with dual organ or previous transplantation and those with missing survival data were excluded. Mortality during the first 30 days after LT was the primary outcome variable. RESULTS: The yearly trends indicate a statistically significant reduction in the 30-day mortality during the study period (P < 0.001, overall mortality: 5.5%) which has continued in the post-LAS era (P = 0. 014, overall mortality: 3.6%). Among patients with 30-day mortality, "primary non-function" (n = 118, 72.8%) was reported as the most common etiology. Transplant indication of vascular diseases, history of non-transplant cardiac or lung surgery, mean pulmonary pressures >35 mm Hg, disabled functional status, ECMO support, high LAS, ischemic time >6 hours, and blunt injury as the mechanism of donor death are independently associated with 30-day mortality. CONCLUSION: The incidence of early mortality after LT continues to decline in the post-LAS era. Apart from the mechanism of donor death and ischemic time, early mortality appears to be primarily driven by the recipient characteristics.

The performance of 9-11-year-old children using an SSVEP-based BCI for target selection.

OBJECTIVE: In this paper, we report the performance of 9-11-year-old children using a steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) and provide control data collected from adults for comparison. Children in our study achieved a much higher performance (79% accuracy; average age 9.64 years old) than the only previous investigation of children using an SSVEP-based BCI (∼50% accuracy; average age 9.86 years old). APPROACH: Experiments were conducted in two phases, a short calibration phase and a longer experimental phase. An offline analysis of the data collected during the calibration phase was used to set two parameters for a classifier and to screen participants who did not achieve a minimum accuracy of 85%. MAIN RESULTS: Eleven of the 14 children and all 11 of the adults who completed the calibration phase met the minimum accuracy requirement. During the experimental phase, children selected targets with a similar accuracy (79% for children versus 78% for adults), latency (2.1 s for children versus 1.9 s for adults), and bitrate (0.50 bits s-1 for children and 0.56 bits s-1 for adults) as adults. SIGNIFICANCE: This study shows that children can use an SSVEP-based BCI with higher performance than previously believed and is the first to report the performance of children using an SSVEP-based BCI in terms of latency and bitrate. The results of this study imply that children with severe motor disabilities (such as locked-in syndrome) may use an SSVEP-based BCI to restore/replace the ability to communicate.

Evaluation of current strategies for surveillance and management of donor-specific antibodies: Single-center study.

BACKGROUND: Although the presence of donor-specific antibodies (DSA) is known to impact lung allograft, limited data exist regarding DSA management. METHODS: We did a retrospective study at our center evaluating DSA management in adult lung transplant recipients undergoing lung transplantation between January 1, 2010 and June 30, 2014. Study follow-up was completed through October 2017. All recipients were stratified into 2 groups based on the presence or absence of DSA. Those with DSA were evaluated for the impact of treatment of DSA. The primary outcomes were postlung transplant survival and freedom from bronchiolitis obliterans syndrome (BOS), subset of chronic lung allograft dysfunction (CLAD). Simon-Makuch method was used to estimate overall survival and BOS-free survival to account for DSA as time-dependent covariate. Survival differences between the groups were analyzed using time-dependent Cox proportional hazards model. RESULTS: Sixty-four percent of 194 total subjects developed post-lung transplant DSA. Overall survival was different with worse survival in the DSA positive group that never cleared DSA (P = .002). BOS-free survival was lower, but did not reach significance in this group. Response to treatment was poor, with only 12 of 47 (25.5%) who received treatment demonstrating clearance of DSA. CONCLUSIONS: Donor-specific antibodies prevalence is high after lung transplantation. Clearance of DSA correlated with improved outcomes. Current therapeutic strategies against DSA are relatively ineffective. Multicenter collaborative studies will be required to evaluate current treatment strategies and other innovative modalities.

Characteristics and outcomes among patients with need for early dialysis after lung transplantation surgery.

BACKGROUND: With the introduction of lung allocation score (LAS), increasingly sicker patients are undergoing lung transplantation (LT). This study was conducted to determine the time trends in need for dialysis after LT, identify variables independently associated with need for dialysis, and evaluate its association with 1- and 5-year mortality. METHODS: We queried the United Network of Organ Sharing database for adult patients undergoing LT between 1994 and 2014. We excluded patients with simultaneous dual organ transplantation and where data regarding the need for dialysis were not available. RESULTS: Time trends in the yearly incidence of the need for dialysis showed a gradual increase (P = .012). In the post-LAS era, ethnicity, underlying diagnosis, estimated GFR <90 mL/min/1.73 m2 and mean pulmonary pressures>35 mm Hg, ventilator or extracorporeal membrane oxygenation support at LT, and >20% increase in serum creatinine between listing and match were independently associated with the need for dialysis. Patients with need for dialysis had significantly increased hazard of 1-year (n = 13 849; adjusted hazard ratio, 95% CI:7.23, 6.2-8.4, P < .001) and 5-year mortality (n = 7287; adjusted hazard ratio, 95% CI:3.96, 3.43-4.56, P < .001). CONCLUSIONS: There is a gradual increase in the incidence of the need for early dialysis after LT, and these patients have significantly worse early and late survival. Several pre-transplant recipient characteristics are independently associated with the need for dialysis.

Interaction of pre-transplant recipient characteristics and renal function in lung transplant survival.

BACKGROUND: There has been little investigation into the potential interaction of recipient characteristics with the association of pre-transplant renal functions and survival after lung transplantation. In this study we tested the hypothesis that association of pre-transplant renal function and post-transplant mortality varies among recipient subgroups. METHODS: We queried the United Network for Organ Sharing (UNOS) database for adult patients (≥18 years of age) undergoing lung transplantation between May 2005 and March 2015. The study population (n = 15,540) was split into 3 groups (90 to 150, 60 to 89.9 and 30 to 59.9 ml/min/1.73 m2) based on the estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation) at the time of listing. We utilized multivariable inverse probability weighted Cox proportional hazard models to compare the association of glomerular filtration rate (GFR) groups with mortality among recipient subgroups. RESULTS: Overall, there was an independent and graded inverse association between the estimated GFR (eGFR) and mortality, with the hazard of mortality significantly rising with listing eGFR <60 ml/min/1.73 m2. The association between low eGFR and mortality was more consistent and stronger for older (>45 years), non-African-American and non-diabetic patients as well as those with low lung allocation score (LAS <40). Among the diagnosis groups, patients with vascular diseases had the strongest association between low eGFR and poor survival. Sensitivity analyses conducted using an alternate equation to estimate the GFR (Modification of Diet in Renal Disease) supported these associations. CONCLUSIONS: Prognostic significance of pre-transplant renal functions varies significantly among recipient subgroups. It may be appropriate to develop a customized approach toward assessing and interpreting renal function to determine transplant candidacy.

Predictors of outcome among patients on extracorporeal membrane oxygenation as a bridge to lung transplantation.

BACKGROUND: There is a lack of data regarding clinical variables associated with successful bridge to lung transplantation (LT) using extracorporeal membrane oxygenation (ECMO) support. METHODS: We reviewed the institutional database for patients supported with veno-venous (VV) or veno-arterial ECMO as a bridge to LT (n=25; mean age: 50.6±14.2 years). We recorded clinical and laboratory variables, findings on echocardiogram and development of organ dysfunction along with hospital and one-year survival. Variables were compared between patients successfully bridged to LT versus those who were not. RESULTS: The most common diagnostic group was interstitial lung disease (18/25, 72%). VV-ECMO was used in the majority (84%). Fifteen patients (60%) were successfully bridged to LT, and the majority were alive at 1 year (14/15, 93.3%). The presence of right ventricular systolic dysfunction on pre-ECMO echocardiogram was associated with increased risk of unsuccessful bridging (OR, 95% CI: 2.67, 1.01-6.99, P=.041). While on ECMO, trough albumin levels <2.5 gm%, peak blood urea nitrogen levels >35 mg/dL and positive fluid balance were also associated with failure to bridge to LT. CONCLUSIONS: Among patients awaiting LT, the presence of RV systolic dysfunction before ECMO initiation along with worsening renal functions, low albumin levels, and volume overload is associated with poor outcomes.

Association of pretransplant kidney function with outcomes after lung transplantation.

PURPOSE: There is a lack of data regarding the independent association of pretransplant kidney function with early and late outcomes among lung transplant (LT) recipients. METHODS: We queried the United Network for Organ Sharing database for adult patients (≥18 years of age) undergoing LT between 1987 and 2013. Glomerular filtration rate (GFR) was estimated using the modification of diet in renal disease (MDRD) and the Chronic kidney disease epidemiology collaboration (CKD-EPI) equations. The study population was split into four groups (>90, 60-90, 45-59.9, and <45 mL/min/1.73 m2 ) based on the estimated GFR at the time of listing. RESULTS: Overall, there was a good correlation between the GFR estimated from the two equations (n=17884, Pearson r=.816, P<.001). There was a consistent and independent association of worse early and late outcomes with declining GFR throughout the spectrum including those above 60 mL/min/1.73 m2 (P<.001 for overall comparisons). Although GFR<45 mL/min/1.73 m2 was associated with worse early and late survival, patients with GFR 45-59.9 mL/min/1.73 m2 do not appear to have survival advantage beyond 3 years post-transplant. CONCLUSION: There is a good correlation between GFR estimated using MDRD and CKD-EPI equations among patients being considered for LT. Early and late outcomes after LT worsen in a linear fashion with progressively lower pretransplant GFR.

Hospital length of stay after lung transplantation: Independent predictors and association with early and late survival.

BACKGROUND: Duration of index hospitalization after lung transplantation (LTx) is an important variable that has not received much attention. We sought to determine independent predictors of prolonged hospital length of stay (LOS) and its association with early and late outcomes. METHODS: The United Network of Organ Sharing database was queried for adult patients undergoing LTx between 2006 and 2014 (N = 14,320). Patients with dual organ or previous transplantation and patients who died during the first 25 days after LTx were excluded (n = 12,647, mean age 55.2 years ± 13.1). Primary outcome was prolonged LOS (>25 days) (3,251/12,647; 25.7%). Donor, recipient, and procedure-related variables were analyzed as potential predictors of prolonged LOS. Association of prolonged LOS with 1-year and 5-year survival was evaluated using Cox proportional hazards analysis. RESULTS: Independent predictors of prolonged LOS included serum albumin, lung allocation score, functional status, and need of extracorporeal membrane oxygenation or ventilator support at the time of transplant; donor age >40 years; gender mismatch (female donor to male recipient); donor body mass index; African American ethnicity; ischemic time >6 hours; and double LTx. Prolonged LOS was independently associated with increased mortality at 1 year (hazard ratio, 3.96; 95% confidence interval, 3.48-4.50; p < 0.001) and 5 years (hazard ratio, 2.00; 95% confidence interval, 1.79-2.25; p < 0.001). CONCLUSIONS: A significant proportion of patients have a prolonged LOS after LTx, and several recipient, donor, and procedure-related variables are independent predictors of this outcome. Patients with prolonged LOS after LTx have significantly increased risk of death at 1 year and 5 years.