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.

The role of posttraumatic stress symptoms on memory complaints and performance in active-duty service members.

OBJECTIVE: Memory complaints are the most common form of cognitive limitation reported by military service members, but prior research suggests that posttraumatic stress symptoms (PTSS) may account for the link between subjective cognitive complaints and objective cognitive performance. The mechanisms underlying this relationship are largely unknown, including whether the finding applies to memory complaints and performance, which clinical dimensions are involved, and how the association varies when memory complaints are non-credible. METHOD: Using a sample of 196 US military service members, the present study aims to address these gaps by modeling the relationship between objective memory performance and plausible/implausible subjective memory complaints, then evaluating how the association is influenced by PTSS and clinical traits commonly found within PTSS (e.g. depression, anxiety, and somatic concerns). RESULTS: Overall memory complaints were associated with immediate and delayed recall, but both associations were fully mediated by PTSS (95% CI -0.14, -0.01; 95% CI -0.14, -0.02, respectively). Implausible memory complaints, however, were inconsistently linked to memory performance, and no PTSS mediation was observed. Of the clinical traits, only depression moderated the impact of PTSS, specifically by influencing the link between PTSS and overall memory complaints (ß = -0.02, SE = 0.004, p < .001). CONCLUSIONS: These results corroborate the importance of assessment for PTSS and depression in service members who report subjective memory complaints and highlight how targeted intervention for these conditions may play a key role in the management of memory complaints.

Gender and ethnic/racial diversity in clinical neuropsychology: Updates from the AACN, NAN, SCN 2020 practice and "salary survey".

OBJECTIVE: Examination of gender and diversity issues within clinical neuropsychology, using data from the 2020 professional practice and "salary survey." METHODS: Clinical neuropsychologists in the U.S. and Canada were invited to participate in an online survey. The final sample consisted of 1677 doctoral-level practitioners. RESULTS: Approximately, 60% of responding neuropsychologists are women and 53.8% of those women identify as early career psychologists (ECPs). Conversely, a majority of men in the sample are advanced career psychologists (ACPs). Both genders work predominantly in institutions, but more men than women work in private practice. ACP men produce a greater number of peer-reviewed publications and conference presentations. Across all work settings, women earn significantly less than men, and are less satisfied with their incomes. Establishing and maintaining family life is the biggest obstacle to attaining greater income and job satisfaction for both genders. Ethnic/racial minority status was identified in 12.9% of respondents, with 59.2% being ECPs. Job satisfaction and hostility in the workplace vary across ethnic/racial minority groups. Hispanic/Latino(a) and White neuropsychologists report higher incomes, but there were no statistically significant differences between any of the groups. CONCLUSIONS: Income and select practice differences persist between female and male neuropsychologists. There is a slow rate of increased ethnic/racial diversity over time, which is much more apparent among early career practitioners. Trajectories and demographics suggest that the gender income gap is unlikely to be improved by the next survey iteration in 2025, whereas it is very likely that ethnic/racial diversity will continue to increase gradually.

Forensic neuropsychology: History and current status.

Objective:This review provides a summary of historical details and current practice activities related to Forensic Neuropsychology (FN). Under the auspices of the American Board of Clinical Neuropsychology (ABCN), the Forensic Neuropsychology Special Interest Group (FNSIG) views the FN as a subspecialty, which has developed over time as the straightforward result of more than 20 years of numerous publications, extensive continuing education, focused research and growth of forensic practice within neuropsychology. In this article, the FNSIG core work group documents and integrates information that is the basis of efforts to consolidate practice knowledge and facilitate attainment of forensic practice competencies by clinical neuropsychologists. Method:Overview of continuing education topics at professional conferences, search results that identify relevant books and peer-reviewed publications, as well as pertinent findings across years of large-scale national survey results. Results:Relevant evidence has shown for decades that FN is prominent within Clinical Neuropsychology as practiced in the United States and Canada. A majority of U.S. neuropsychologists have received FN training and provide forensic evaluation services. FN practice time per week is considerable for many practitioners, and across survey epochs has been shown to be increasing. Conclusion:The present review leads to the conclusion that in the interest of promoting the acquisition of competence, FN practice should remain a focal point of training and continuing education. Alternate routes to attain competence are discussed, as are ongoing professional activities that undoubtedly will ensure continued growth of, and interest in, the subspecialty of FN.

Emerging Therapeutic Options for Refractory Pulmonary Sarcoidosis: The Evidence and Proposed Mechanisms of Action.

Sarcoidosis is a systemic disease with heterogenous clinical phenotypes characterized by non-necrotizing granuloma formation in affected organs. Most disease either remits spontaneously or responds to corticosteroids and second-line disease-modifying therapies. These medications are associated with numerous toxicities that can significantly impact patient quality-of-life and often limit their long-term use. Additionally, a minority of patients experience chronic, progressive disease that proves refractory to standard treatments. To date, there are limited data to guide the selection of alternative third-line medications for these patients. This review will outline the pathobiological rationale behind current and emerging therapeutic agents for refractory or drug-intolerant sarcoidosis and summarize the existing clinical evidence in support of their use.

Inefficient Attentional Control Explains Verbal-Memory Deficits Among Military Veterans With Posttraumatic Reexperiencing Symptoms.

Among individuals with posttraumatic stress disorder (PTSD), verbal learning and memory are areas of weakness compared with other cognitive domains (e.g., visuospatial memory). In this study, previously deployed military veterans completed clinical assessments of word memory and vocabulary (n = 243) and a laboratory task measuring encoding, free recall, repetition priming, and recognition of words (n = 147). Impaired verbal memory was selectively related to reexperiencing symptoms of PTSD but was not associated with other symptom groupings or blast-induced traumatic brain injury. Implicit priming of response times following word repetition was also unrelated to clinical symptoms. Instead, slowed response times during encoding explained associations between reexperiencing and memory performance. These findings are consistent with alterations in attentional control explaining PTSD-related verbal-memory deficits. Such findings have implications for understanding trauma-focused psychotherapy and recovery, which may depend on efficient attentional processing of words to alter posttraumatic reexperiencing symptoms.

Plasma Neurofilament Light and Future Declines in Cognition and Function in Alzheimer's Disease in the FIT-AD Trial.

BACKGROUND: Utilities of blood-based biomarkers in Alzheimer's disease (AD) clinical trials remain unknown. OBJECTIVE: To evaluate the ability of plasma neurofilament light chain (NfL) to predict future declines in cognition and activities of daily living (ADL) outcomes in 26 older adults with mild-to-moderate AD dementia from the FIT-AD Trial. METHODS: Plasma NfL was measured at baseline and 3 and 6 months. Cognition and ADL were assessed using the AD Assessment Scale-Cognition (ADAS-Cog) and AD Uniform Dataset Instruments and Disability Assessment for Dementia (DAD), respectively, at baseline, 3, 6, 9, and 12 months. Linear mixed effects models were used to examine the associations between baseline or change in plasma NfL and changes in outcomes. RESULTS: Higher baseline plasma NfL was associated with greater rate of decline in ADAS-Cog from baseline to 6 months (standardized estimate of 0.00462, p = 0.02853) and in ADL from baseline to 12 months (standardized estimate of -0.00284, p = 0.03338). Greater increase in plasma NfL in short term from baseline to 3 months was associated with greater rate of decline in memory and ADL from 3 to 6 months (standardized estimate of -0.04638 [0.003], p = 0.01635; standardized estimate of -0.03818, p = 0.0435) and greater rate of decline in ADL from 3 to 12 month (standardized estimate of -0.01492, p = 0.01082). CONCLUSION: This study demonstrated that plasma NfL might have the potential to predict cognitive and function decline up to 12 months. However, future studies with bigger sample sizes need to confirm the findings.

Clinical neuropsychology in Canada: Results from the 2020 AACN, NAN, SCN professional practice and "salary survey".

Objective: The current study summarizes the results of a 2020 survey that solicited information regarding backgrounds, beliefs, practices, and incomes of clinical neuropsychologists who practice in Canada. Methods: Clinical neuropsychologists who practice in Canada were invited to participate in an online survey that was available from 1/17/20 to 4/02/20. Available survey findings were obtained from 111 respondents, which reflects a response rate of 51.3% of the 216 doctoral-level Canadian neuropsychologists identified in at least one major North American or international professional organization membership list (AACN, INS, NAN, or SCN). Results: Most of the current respondents were White/Caucasian women who identified as adult providers and worked full-time in urban institutional settings. Four Canadian provinces (Alberta, British Columbia, Ontario, Quebec) accounted for more than 91% of the current respondent sample. Incomes and career satisfactions were largely encouraging, though some important variations were noted by province, work setting, and professional identity. Incomes were significantly associated with forensic practices and years of clinical experience. Most respondents made use of technician support in their practices, largely to increase productivity and patient volume. Only a small minority of respondents were board-certified and there was generally limited interest in future board certification. Conclusions: While important similarities were observed in the current Canadian sample relative to recent survey findings obtained in a U.S. sample, results also reveal a number of important differences that serve as important areas of future consideration.

Cognitive Effects of Aerobic Exercise in Alzheimer's Disease: A Pilot Randomized Controlled Trial.

BACKGROUND: Aerobic exercise has shown inconsistent cognitive effects in older adults with Alzheimer's disease (AD) dementia. OBJECTIVE: To examine the immediate and longitudinal effects of 6-month cycling on cognition in older adults with AD dementia. METHODS: This randomized controlled trial randomized 96 participants (64 to cycling and 32 to stretching for six months) and followed them for another six months. The intervention was supervised, moderate-intensity cycling for 20-50 minutes, 3 times a week for six months. The control was light-intensity stretching. Cognition was assessed at baseline, 3, 6, 9, and 12 months using the AD Assessment Scale-Cognition (ADAS-Cog). Discrete cognitive domains were measured using the AD Uniform Data Set battery. RESULTS: The participants were 77.4±6.8 years old with 15.6±2.9 years of education, and 55% were male. The 6-month change in ADAS-Cog was 1.0±4.6 (cycling) and 0.1±4.1 (stretching), which were both significantly less than the natural 3.2±6.3-point increase observed naturally with disease progression. The 12-month change was 2.4±5.2 (cycling) and 2.2±5.7 (control). ADAS-Cog did not differ between groups at 6 (p = 0.386) and 12 months (p = 0.856). There were no differences in the 12-month rate of change in ADAS-Cog (0.192 versus 0.197, p = 0.967), memory (-0.012 versus -0.019, p = 0.373), executive function (-0.020 versus -0.012, p = 0.383), attention (-0.035 versus -0.033, p = 0.908), or language (-0.028 versus -0.026, p = 0.756). CONCLUSION: Exercise may reduce decline in global cognition in older adults with mild-to-moderate AD dementia. Aerobic exercise did not show superior cognitive effects to stretching in our pilot trial, possibly due to the lack of power.

Professional practices, beliefs, and incomes of U.S. neuropsychologists: The AACN, NAN, SCN 2020 practice and "salary survey".

OBJECTIVE: This portion of the 2020 survey updates practice information, beliefs, and income data of clinical neuropsychologists who practice within the United States. Methods: Doctoral-level neuropsychology practitioners were invited via numerous methods, with multiple reminders, to participate in a web-based survey from January 17 through April 2, 2020. The useable U.S. sample of 1677 doctoral-level practitioners was 6.2% larger than the comparable group in the prior 2015 practice survey. Results: Whereas women practitioners predominate, which continues a steeply increasing trend across time, increases in overall ethnic/racial diversity continue at a slow pace. Median age has remained very similar over the last 30 years, reflecting a continuous influx of young practitioners. A relatively small minority of neuropsychologists work part time. The proportion of board-certified neuropsychologists continues to show meaningful increase; interest in subspecialization certification is relatively high. Reliance on technicians remains popular, especially for neuropsychologists who work in institutions or are board certified. Although implementation of new CPT codes in 2019 and related payor policies appear to have had more negative than positive effects, psychology-related annual incomes of neuropsychologists have again increased compared to prior surveys. Variables such as specific work setting, state, region, years in practice, forensic practice hours, board certification, and basis for determining income (e.g. hours billed, revenue collected, relative value units) have an impact on income. More than half of practitioners engage in forensic neuropsychology, with the number of related practice hours per week again increasing. There is very high agreement regarding the use of response validity measures in clinical practice and forensic practice. Neurologists remain the number one referral source whether working in an institution, private practice, or a combination of both, and regardless of maintaining a pediatric, adult, or lifespan practice. Career satisfaction ratings for income, job, and work-life balance remain high, with the majority of ratings regarding the future of the specialty in the positive range. Additional data summaries related to a wide range of professional and practice topics are provided. Conclusions: Updating and comparing survey information at five-year intervals continues to provide insights and perspectives regarding relative stabilities and changes in practice activities, beliefs, and incomes of U.S. clinical neuropsychologists. Such information also provides guidance regarding the future of the specialty.

Professional Practices, Beliefs, and Incomes of Postdoctoral Trainees: The AACN, NAN, SCN 2020 Practice and 'Salary Survey'.

OBJECTIVE: Within a portion of the 2020 professional practice and "salary survey," to update key information regarding neuropsychology postdoctoral trainees. METHODS: Postdoctoral trainees were contacted via a variety of membership listings, including the listserv used by the program directors of the Association of Postdoctoral Programs in Clinical Neuropsychology (APPCN). Invitations sent in multiple waves to members of numerous neuropsychological organizations via e-messages and physical postcards included the request that postdoctoral trainees participate. The survey website was opened on January 17, 2020 and closed on April 2, 2020, during which time a total of 178 postdoctoral trainees in the USA and 3 in Canada participated. RESULTS: Response rate was estimated to be 56.4%, which adequately represents the target sample. The modal postdoctoral trainee is a woman whose internship was American Psychological Association (APA)-accredited and whose postdoctoral training is in an APPCN program that adheres to Houston Conference training guidelines. Extensive clinical experiences in neuropsychology in the form of externship practica and during internship were reported by the majority of trainees prior to postdoctoral training. There are few differences between APPCN and non-APPCN trainees and reported training experiences. Job satisfaction is high. Salaries appear to have increased substantially in recent years. There is universal interest in pursuing board certification. Support for the empirical foundations justifying assessment of response validity is high. CONCLUSIONS: Surveys of postdoctoral trainees continue to provide valuable perspectives regarding training background, clinical experiences, practice beliefs, and incomes of individuals who will soon launch their careers in clinical neuropsychology.

Antimicrobial peptide activity is anticorrelated with lipid a leaflet affinity.

The activity of antimicrobial peptides (AMPs) has significant bacterial species bias, the mechanisms of which are not fully understood. We employed single-molecule tracking to measure the affinity of three different AMPs to hybrid supported bilayers composed of lipid A extracted from four different Gram negative bacteria and observed a strong empirical anticorrelation between the affinity of a particular AMP to a given lipid A layer and the activity of that AMP towards the bacterium from which that lipid A was extracted. This suggested that the species bias of AMP activity is directly related to AMP interactions with bacterial outer membranes, despite the fact that the mechanism of antimicrobial activity occurs at the inner membrane. The trend also suggested that the interactions between AMPs and the outer membrane lipid A (even in the absence of other components, such as lipopolysaccharides) capture effects that are relevant to the minimum inhibitory concentration.

Semi-supervised Training Data Selection Improves Seizure Forecasting in Canines with Epilepsy.

OBJECTIVE: Conventional selection of pre-ictal EEG epochs for seizure prediction algorithm training data typically assumes a continuous pre-ictal brain state preceding a seizure. This is carried out by defining a fixed duration, pre-ictal time period before seizures from which pre-ictal training data epochs are uniformly sampled. However, stochastic physiological and pathological fluctuations in EEG data characteristics and underlying brain states suggest that pre-ictal state dynamics may be more complex, and selection of pre-ictal training data segments to reflect this could improve algorithm performance. METHODS: We propose a semi-supervised technique to select pre-ictal training data most distinguishable from interictal EEG according to pre-specified data characteristics. The proposed method uses hierarchical clustering to identify optimal pre-ictal data epochs. RESULTS: In this paper we compare the performance of a seizure forecasting algorithm with and without hierarchical clustering of pre-ictal periods in chronic iEEG recordings from six canines with naturally occurring epilepsy. Hierarchical clustering of training data improved results for Time In Warning (TIW) (0.18 vs. 0.23) and False Positive Rate (FPR) (0.5 vs. 0.59) when evaluated across all subjects (p<0.001, n=6). Results were mixed when evaluating TIW, FPR, and Sensitivity for individual dogs. CONCLUSION: Hierarchical clustering is a helpful method for training data selection overall, but should be evaluated on a subject-wise basis. SIGNIFICANCE: The clustering method can be used to optimize results of forecasting towards sensitivity or TIW or FPR, and therefore can be useful for epilepsy management.

Blast concussion and posttraumatic stress as predictors of postcombat neuropsychological functioning in OEF/OIF/OND veterans.

OBJECTIVES: Many combat veterans exhibit cognitive limitations of uncertain origin. In this study, we examined factors that predict cognitive functioning by considering effects of blast-related concussion (BRC), non-blast-related concussion (NBRC), and posttraumatic stress disorder (PTSD) symptoms. Analyses specifically tested whether (a) BRC and NBRC were distinct in their prediction of cognitive performance; (b) a dose-response relationship existed between recurrent concussion (BRC and NBRC) and cognitive impairment; and (c) PTSD symptoms mediated the relationship between BRC and cognitive performance. METHOD: Two hundred eighty veterans with combat zone deployment histories completed semistructured clinical interviews to define BRC and NBRC histories, current and past mental health disorders, and dimensional ratings of PTSD symptomatology. Participants were also administered a number of neuropsychological measures to appraise cognitive functioning. RESULTS: A structural equation model (SEM) suggested that BRC and NBRC were not distinct in their prediction of cognitive performance, and there was no evidence that recurrent concussion (blast or nonblast) was directly associated with cognitive performance. BRC was significantly associated with PTSD symptoms (r = .24), PTSD symptoms were significantly associated with cognitive performance in the SEM (r = -.27), and PTSD symptoms significantly mediated the link between BRC and cognitive performance (p = .03). CONCLUSIONS: These results suggest that concussion history fails to directly contribute to cognitive performance, regardless of mechanism (blast or nonblast) and recurrence. BRC is nonetheless unique in its contribution to PTSD and PTSD-related cognitive deficits. Results support interventions specific to PTSD management in the interest of promoting neuropsychological functioning among war veterans. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

The impact of PTSD and mTBI on the relationship between subjective and objective cognitive deficits in combat-exposed veterans.

OBJECTIVE: Cognitive complaints, such as attentional or memory concerns, are commonly reported by veterans diagnosed with posttraumatic stress disorder (PTSD) or a history of mild traumatic brain injury (mTBI). The degree to which those complaints actually map onto measurable cognitive deficits is unclear and is likely complicated by the severity of trauma-related sequelae. In the present study we sought to characterize the degree to which PTSD symptoms and mTBI accounted for the relationship of subjective cognitive complaints to objective cognitive performance, with the goal of facilitating the accurate assessment of trauma-exposed veterans complaining of cognitive decline. METHOD: A sample of 203 U.S. military veterans previously deployed to Iraq and/or Afghanistan were assessed for PTSD severity, history of blast and impact mTBI, objective cognitive function, and subjective cognitive complaints. Separate mediation analyses were conducted to explore the degree that PTSD severity, blast mTBI severity, and impact mTBI severity influenced the association between subjective cognitive complaints and objective cognitive performance. Models reflecting significant mediation were followed by post hoc moderated mediation analyses. RESULTS: Subjective cognitive complaints and objective cognitive performance were significantly associated (ß = -6.49, SE = 2.85, p = .03), but this relationship was mediated by PTSD severity (ß= -2.95, SE = 2.86, p = .30). PTSD mediation was not moderated by either blast or impact mTBI. CONCLUSION: The present results delineate the prominent impact of PTSD symptoms, relative to blast and impact mTBI, on cognition following combat. These findings highlight the importance of assessing for trauma-related psychopathology in those seeking neuropsychological assessment or rehabilitative care for cognitive complaints. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Surface-Templated Nanobubbles Protect Proteins from Surface-Mediated Denaturation.

In this Letter, we report that surface-bound nanobubbles reduce protein denaturation on methylated glass by irreversible protein shell formation. Single-molecule total internal reflection fluorescence (SM-TIRF) microscopy was combined with intramolecular Förster resonance energy transfer (FRET) to study the conformational dynamics of nitroreductase (NfsB) on nanobubble-laden methylated glass surfaces, using reflection brightfield microscopy to register nanobubble locations with NfsB adsorption. First, NfsB adsorbed irreversibly to nanobubbles with no apparent desorption after 5 h. Moreover, virtually all (96%) of the NfsB molecules that interacted with nanobubbles remained folded, whereas less than 50% of NfsB molecules remained folded in the absence of nanobubbles on unmodified silica or methylated glass surfaces. This trend was confirmed by ensemble-average fluorometer TIRF experiments. We hypothesize that nanobubbles reduce protein damage by passivating strongly denaturing topographical surface defects. Thus, nanobubble stabilization on surfaces may have important implications for antifouling surfaces and improving therapeutic protein storage.

Efficacy and mechanisms of combined aerobic exercise and cognitive training in mild cognitive impairment: study protocol of the ACT trial.

BACKGROUND: Developing non-pharmacological interventions with strong potential to prevent or delay the onset of Alzheimer's disease (AD) in high-risk populations is critical. Aerobic exercise and cognitive training are two promising interventions. Aerobic exercise increases aerobic fitness, which in turn improves brain structure and function, while cognitive training improves selective brain function intensively. Hence, combined aerobic exercise and cognitive training may have a synergistic effect on cognition by complementary strengthening of different neural functions. Few studies have tested the effects of such a combined intervention, and the findings have been discrepant, largely due to varying doses and formats of the interventions. METHODS/DESIGN: The purpose of this single-blinded, 2 × 2 factorial phase II randomized controlled trial is to test the efficacy and synergistic effects of a 6-month combined cycling and speed of processing training intervention on cognition and relevant mechanisms (aerobic fitness, cortical thickness, and functional connectivity in the default mode network) in older adults with amnestic mild cognitive impairment. This trial will randomize 128 participants equally to four arms: cycling and speed of processing, cycling only, speed of processing only, or attention control for 6 months, and then follow them for another 12 months. Cognition and aerobic fitness will be assessed at baseline and at 3, 6, 12, and 18 months; cortical thickness and functional connectivity at baseline and at 6, 12, and 18 months; Alzheimer's disease (AD) conversion at 6, 12, and 18 months. The specific aims are to (1) determine the efficacy and synergistic effects of the combined intervention on cognition over 6 months, (2) examine the underlying mechanisms of the combined intervention, and (3) calculate the long-term effect sizes of the combined intervention on cognition and AD conversion. The analysis will use intention-to-treat and linear mixed-effects modeling. DISCUSSION: This trial will be among the first to test the synergistic effects on cognition and mechanisms (relevant to Alzheimer's-associated neurodegeneration) of a uniquely conceptualized and rigorously designed aerobic exercise and cognitive training intervention in older adults with mild cognitive impairment. It will advance Alzheimer's prevention research by providing precise effect-size estimates of the combined intervention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03313895 . Registered on 18 October 2017.

Contact Line Pinning Is Not Required for Nanobubble Stability on Copolymer Brushes.

Whereas nanobubble stability on solid surfaces is thought to be based on local surface structure, in this work, we show that nanobubble stability on polymer brushes does not appear to require contact-line pinning. Glass surfaces were functionalized with copolymer brushes containing mixtures of hydrophobic and hydrophilic segments, exhibiting water contact angles ranging from 10 to 75°. On unmodified glass, dissolution and redeposition of nanobubbles resulted in reformation in mostly the same locations, consistent with the contact line pinning hypothesis. However, on polymer brushes, the nucleation sites were random, and nanobubbles formed in new locations upon redeposition. Moreover, the presence of stable nanobubbles was correlated with global surface wettability, as opposed to local structure, when the surface exceeded a critical water contact angle of 50 or 60° for polymers containing carboxyl or sulfobetaine groups, respectively, as hydrophilic side chains. The critical contact angles were insensitive to the identity of the hydrophobic segments.

Single-Molecule Resolution of Antimicrobial Peptide Interactions with Supported Lipid A Bilayers.

The molecular interactions between antimicrobial peptides (AMPs) and lipid A-containing supported lipid bilayers were probed using single-molecule total internal reflection fluorescence microscopy. Hybrid supported lipid bilayers with lipid A outer leaflets and phospholipid (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)) inner leaflets were prepared and characterized, and the spatiotemporal trajectories of individual fluorescently labeled LL37 and Melittin AMPs were determined as they interacted with the bilayer surfaces comprising either monophosphoryl or diphosphoryl lipid A (from Escherichia coli) to determine the impact of electrostatic interactions. Large numbers of trajectories were obtained and analyzed to obtain the distributions of surface residence times and the statistics of the spatial trajectories. Interestingly, the AMP species were sensitive to subtle differences in the charge of the lipid, with both peptides diffusing more slowly and residing longer on the diphosphoryl lipid A. Furthermore, the single-molecule dynamics indicated a qualitative difference between the behavior of AMPs on hybrid Lipid A bilayers and on those composed entirely of DOPE. Whereas AMPs interacting with a DOPE bilayer exhibited two-dimensional Brownian diffusion with a diffusion coefficient of ∼1.7 µm2/s, AMPs adsorbed to the lipid A surface exhibited much slower apparent diffusion (on the order of ∼0.1 µm2/s) and executed intermittent trajectories that alternated between two-dimensional Brownian diffusion and desorption-mediated three-dimensional flights. Overall, these findings suggested that bilayers with lipid A in the outer leaflet, as it is in bacterial outer membranes, are valuable model systems for the study of the initial stage of AMP-bacterium interactions. Furthermore, single-molecule dynamics was sensitive to subtle differences in electrostatic interactions between cationic AMPs and monovalent or divalent anionic lipid A moieties.

Predictors of Postdeployment Functioning in Combat-Exposed U.S. Military Veterans.

Posttraumatic stress disorder (PTSD) and sequelae of mild traumatic brain injury (mTBI) are presumed to contribute to reintegration difficulties in combat-exposed veterans. Yet their relative impacts on postdeployment functioning are not well understood. The current study used structural equation modeling (SEM) to clarify the extent to which symptoms of internalizing disorders (e.g., depression, anxiety), mTBI symptoms, and cognitive performance are associated with functional impairment in 295 combat-exposed veterans. SEM results showed that internalizing symptoms most significantly predicted functional impairment (r = 0.72). Blast mTBI and cognitive performance were associated with internalizing (r = 0.24 and -0.25, respectively), but functional impairment was only modestly related to cognition (r = -0.17) and unrelated to mTBI. These results indicate that internalizing symptoms are the strongest predictor of functioning in trauma-exposed veterans, exceeding the effects of mTBI and cognitive performance. This evidence supports prioritizing interventions that target internalizing psychopathology to improve functioning in cases of co-occurring PTSD and mTBI.