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Recent clinical studies show activating multiple innate immune pathways drives robust responses in infection and cancer. Biomaterials offer useful features to deliver multiple cargos, but add translational complexity and intrinsic immune signatures that complicate rational design. Here a modular adjuvant platform is created using self-assembly to build nanostructured capsules comprised entirely of antigens and multiple classes of toll-like receptor agonists (TLRas). These assemblies sequester TLR to endolysosomes, allowing programmable control over the relative signaling levels transduced through these receptors. Strikingly, this combinatorial control of innate signaling can generate divergent antigen-specific responses against a particular antigen. These assemblies drive reorganization of lymph node stroma to a pro-immune microenvironment, expanding antigen-specific T cells. Excitingly, assemblies built from antigen and multiple TLRas enhance T cell function and antitumor efficacy compared to ad-mixed formulations or capsules with a single TLRa. Finally, capsules built from a clinically relevant human melanoma antigen and up to three TLRa classes enable simultaneous control of signal transduction across each pathway. This creates a facile adjuvant design platform to tailor signaling for vaccines and immunotherapies without using carrier components. The modular nature supports precision juxtaposition of antigen with agonists relevant for several innate receptor families, such as toll, STING, NOD, and RIG., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Objectives: Transdiagnostic treatments increasingly include emotion regulation training focused on use of emotional suppression and acceptance. Despite the frequent use of these treatments in depression, little is known about the effects of these strategies in this population., Design: An experimental study., Methods: Eighty Veterans with unipolar depression participated in a study examining effects of these strategies on emotional responding (subjective, behavioural, and physiological). Physiological measures included: heart rate (HR), respiration (Resp), skin conductance (SC), and corrugator electromyography. On Day 1, participants were randomised to one of three conditions (acceptance, suppression, or control) and underwent an autobiographical sad mood induction. On Day 2, participants underwent a similar mood induction one week later., Results: The suppression group demonstrated reduced physiological reactivity (Resp and SC) on Day 1. However, the suppression group reported decreased positive affect on Day 2., Conclusions: Results support short-term effectiveness and longer term costs from suppression use among depressed individuals. Findings may inform application of transdiagnostic emotion regulation treatments and suggest suppression functions differently in depressed versus other clinical populations., (© 2021 British Psychological Society.)

Nanoparticles (NPs) have emerged as a highly useful and clinically translatable drug delivery platform for vast therapeutic payloads. Through the precise tuning of their physicochemical properties, NPs can be engineered to exhibit controlled drug release properties, enhanced circulation times, improved cellular uptake and targeting, and reduced toxicity profiles. Conventional bulk methods for the production of polymeric NPs suffer from the ability to control their size and polydispersity, batch-to-batch variability, significant preparation times, and low recovery. Here, we describe the development and optimization of a high-throughput microfluidic method to produce cargo-less immunomodulatory nanoparticles (iNPs) and their formulation-dependent anti-inflammatory properties for the modulation of lipopolysaccharide (LPS)-induced macrophage responses. Using poly(lactic acid) (PLA) as the core-forming polymer, a rapid and tunable microfluidic hydrodynamic flow-focusing method was developed and optimized to systematically evaluate the role of polymer and surfactant concentration, surfactant chemistry, and flow rate ratio (FRR) on the formation of iNPs. A set of iNPs with 6 different surface chemistries and 2 FRRs was then prepared to evaluate their inherent anti-inflammatory effects using bone marrow-derived macrophages stimulated with the Toll-like receptor 4 agonist, LPS. Finally, a lyophilization study was performed using various cryoprotectants and combinations to identify preferable conditions for iNP storage. Overall, we demonstrate a highly controlled and reproducible method for the formulation of iNPs using microfluidics and their formulation-dependent inherent anti-inflammatory immunomodulatory properties, which represents a potentially promising strategy for the management of inflammation., (© 2021. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison's disease (AD)., Methods: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined., Results: The prevalence of APS-1 was 2.6 cases/million (range 0.5-17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases., Conclusions: In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions., (© 2021. The Author(s).)

Autoimmune diseases like multiple sclerosis (MS), type 1 diabetes, and lupus occur when the immune system attacks host tissue. Immunotherapies that promote selective tolerance without suppressing normal immune function are of tremendous interest. Here, nanotechnology was used for rational assembly of peptides and modulatory immune cues into immune complexes. Complexes containing self-peptides and regulatory nucleic acids reverse established paralysis in a preclinical MS model. Importantly, mice responding to immunotherapy maintain healthy, antigen-specific B and T cell responses during a foreign antigen challenge. A therapeutic library isolating specific components reveals that regulatory nucleic acids suppress inflammatory genes in innate immune cells, while disease-matched peptide sequences control specificity of tolerance. Distinct gene expression profiles in cells and animals are associated with the immune signals administered in particulate and soluble forms, highlighting the impact of biophysical presentation of signals. This work provides insight into the rational manipulation of immune signaling to drive tolerance.

Therapies for autoimmune diseases such as multiple sclerosis and diabetes are not curative and cause significant challenges for patients. These include frequent, continued treatments required throughout the lifetime of the patient, as well as increased vulnerability to infection due to the non-specific action of therapies. Biomaterials have enabled progress in antigen-specific immunotherapies as carriers and delivery vehicles for immunomodulatory cargo. However, most of this work is in the preclinical stage, where small dosing requirements allow for on-demand preparation of immunotherapies. For clinical translation of these potential immunotherapies, manufacturing, preservation, storage, and stability are critical parameters that require greater attention. Here, we tested the stabilizing effects of excipients on the lyophilization of polymeric microparticles (MPs) designed for autoimmune therapy; these MPs are loaded with peptide self-antigen and a small molecule immunomodulator. We synthesized and lyophilized particles with three clinically relevant excipients: mannitol, trehalose, and sucrose. The biophysical properties of the formulations were assessed as a function of excipient formulation and stage of addition, then formulations were evaluated in primary immune cell culture. From a manufacturing perspective, excipients improved caking of lyophilized product, enabled more complete resuspension, increased product recovery, and led to smaller changes in MP size and size distribution over time. Cocultures of antigen-presenting cells and self-reactive T cells revealed that MPs lyophilized with excipients maintained tolerance-inducing function, even after significant storage times without refrigeration. These data demonstrate that excipients can be selected to drive favorable manufacturing properties without impacting the immunologic properties of the tolerogenic MPs., Competing Interests: CJ is an employee of the VA Maryland Health Care System. CJ has equity positions with Avidea Technologies and Cellth Systems, LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gosselin, Noshin, Black and Jewell.)

Introduction: Youth with obesity have abnormal vascular function that relates to the anti-atherogenic adipose-derived hormone, adiponectin. The distribution of adiponectin isomers changes during normal puberty, but there are no data in relation to vascular function. We aimed to evaluate vascular function, adiponectin, and its isomers longitudinally in peri-pubertal youth with obesity and controls., Methods: The study is a cohort longitudinal study involving 30 children and adolescents with obesity (body mass index [BMI] z-score 2.31 ± 0.24; age 12.8 ± 3 years, 17 male participants) and 28 age-/sex-matched healthy controls (12.8 ± 3 years, 14 male participants). Vascular function (flow-mediated dilatation [FMD], glyceryl trinitrate-mediated dilatation [GTN]), total adiponectin and isomers, and laboratory and clinical variables were assessed at 0, 18, and 36 months., Results: FMD and GTN were stable during puberty in both groups, remaining consistently lower in obese children (p = 0.02, p < 0.001). The change in total (p = 0.02) and high-molecular weight (HMW) (p = 0.02) adiponectin differed between the groups: falling in controls by the end of puberty but not falling further during puberty in obesity. In obesity, impaired GTN was associated longitudinally with lower total (B = 7.85, p = 0.006) and HMW (B = 3.72, p = 0.03) adiponectin. In controls, more favourable GTN was longitudinally associated with a lower BMI z-score (B = -3.04, p = 0.027) and lower waist circumference (B = -0.35, p = 0.009)., Conclusions: Vascular dysfunction and lower levels of adiponectin are associated in children and adolescents with obesity during puberty and do not deteriorate further. Healthy children's better vascular function, within the normal range, is associated with a lower BMI z-score and waist circumference., (© 2021 S. Karger AG, Basel.)

Biomaterial carriers offer modular features to control the delivery and presentation of vaccines and immunotherapies. This tunability is a distinct capability of biomaterials. Understanding how tunable material features impact immune responses is important to improve vaccine and immunotherapy design, as well as clinical translation. Here we discuss the modularity of biomaterial properties as a means of controlling encounters with immune signals across scales - tissue, cell, molecular, and time - and ultimately, to direct stimulation or regulation of immune function. We highlight these advances using illustrations from recent literature across infectious disease, cancer, and autoimmunity. As the immune engineering field matures, informed design criteria could support more rational biomaterial carriers for vaccination and immunotherapy.

This study validated the Brief Inventory of Psychosocial Functioning (B-IPF), an abridged version of the 80-item Inventory of Psychosocial Functioning (IPF; Bovin et al., 2018). The B-IPF-a 7-item self-report questionnaire that assesses posttraumatic stress disorder (PTSD)-related psychosocial functional impairment-was developed for use in settings in which the full IPF would be too time intensive to administer. In this study, we examined the psychometric properties of the B-IPF among a sample of 362 veterans recruited from 2 Veterans Affairs hospitals. The B-IPF demonstrated high internal consistency (Cronbach's alpha = .84) and adequate test-retest reliability (r = .65, p < .001). The B-IPF was strongly correlated with the IPF (r = .71, p < .01) and had higher correlations with measures of mental health impairment and quality of life (all rs > ∥.50∥; all ps < .001) than with a measure of physical health impairment (i.e., the Physical Component Summary; r = -.34; p < .001), which demonstrated strong construct validity. In addition, the B-IPF displayed strong criterion-related validity, with higher correlations with a PTSD symptom measure, (r = .63, p < .05), and measures of other internalizing disorders (all rs > .44; all ps < .05) and a lower correlation with a measure of an externalizing disorder (r = .14; p < .05). These results indicate that the B-IPF is a reliable and valid instrument for assessing PTSD-related impairment. The strong psychometric properties of the instrument, in addition to its length, make it ideal for settings in which time is a factor. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objectives: Military sexual trauma (MST) is a pervasive problem among veterans, and is associated with a host of deleterious outcomes. It is, therefore, imperative to identify individuals who have experienced MST so that they can be offered appropriate treatment. To determine how to best identify MST survivors, the current study examined how different assessment modalities might affect MST endorsement, and whether endorsement varied as a product of demographic group membership., Methods: Data from 697 male and female veterans participating in the Veterans' After-Discharge Longitudinal Registry (Project VALOR) were used to examine how three different MST assessment modalities-the Veterans Health Administration screen, a study interview, and a study questionnaire measure-might affect MST endorsement across five different demographic variables (gender, ethnicity, sexual orientation, race, and age). Each participant was evaluated for MST exposure using each of the three assessment modalities., Results: Both assessment modality and demographic membership influenced MST endorsement. MST endorsement on the study measures was consistently twice as large as on the Veterans Health Administration screen, across demographic groups. For men, MST endorsement varied by a factor of 11 across measures, with endorsement being lowest on the Veterans Health Administration screen and highest on the study questionnaire. Although differences were also detected for sexual minority and Black participants, these findings may have been better explained by gender differences., Conclusions: Both assessment modality and demographic membership substantially influenced MST endorsement. Providing a clear rationale for screening and increasing privacy around screening results, particularly for male veterans, may help to facilitate MST disclosure., (Published by Elsevier Inc.)

This study describes the three-phase development and validation of the Inventory of Psychosocial Functioning (IPF), an 80-item, self-report measure of posttraumatic stress disorder (PTSD)-related psychosocial functional impairment. In Phase I, we conducted 12 focus groups with male and female veterans (n = 53) to identify and operationalize the domains of psychosocial impairment associated with PTSD. This information was used to develop the IPF. We subsequently evaluated the psychometric properties of the newly developed inventory in Phases II (n = 276) and III (n = 368) using two independent samples of veterans. We found that the overall IPF score demonstrated stronger correlations with measures of mental health-related impairment (all rs > |.39|; all ps < .05) and weaker correlations with measures of physical health-related impairment (all rs < |.29|; all ps < .05). Overall IPF scores were most strongly associated with PTSD and other disorders associated with the anxious-misery factor of the three-factor model of psychiatric comorbidity (all rs > .56; all ps < .05) and less strongly associated with disorders associated with the fear factor (all rs < .48; all ps < .05) and the externalizing factor (r = .16; p < .05). The IPF demonstrated strong test-retest reliability (r = .77; p < .05). Our results suggest that the IPF is a valid and reliable measure of PTSD-related psychosocial functional impairment. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Objective: The goal of this project was to develop and evaluate a new residency training rotation focused on cognitive-behavioral therapies (CBT) and to assess outcomes across multiple domains., Methods: Data are presented from 30 psychiatry residents. Primary learning-related outcomes included content knowledge, self-efficacy, and attitudes and behavioral intentions towards evidence-based psychotherapies (e.g., CBT)., Results: Residents reported significant increases in CBT knowledge, CBT-specific self-efficacy, overall psychotherapy self-efficacy, belief in patient benefit from CBT, and behavioral intention to use CBT. However, there were almost no changes in attitudes towards evidence-based practice more broadly, with one significant finding showing an increase in skepticism towards such practices., Conclusions: This empirically based example of training program development, implementation, and evaluation appears largely successful and represents one approach for addressing the CBT competency goals outlined by the Accreditation Council for Graduate Medical Education (ACGME) and Milestone Project Guidelines. Despite these initial, positive findings, conclusions should be tempered by limitations of the project design (e.g., the lack of comparison group, absence of objective measures of resident behavioral change, or assessment of the effect of such changes on patient outcomes). Findings highlight the need for continued development and evaluation of training methods in CBT for residency programs.

Research has revealed a significant association between several peritraumatic emotional responses and posttraumatic stress disorder (PTSD). Preliminary research has also linked peritraumatic emotional responses with a diagnosis of major depressive disorder (MDD). The majority of this research has been cross-sectional, thereby making it difficult to determine the extent to which the various peritraumatic emotional responses may increase risk for, or serve as a premorbid marker of, PTSD and MDD. This study examined the longitudinal role of peritraumatic emotional responses on the subsequent development of PTSD and MDD in a sample of US military veterans. Whereas a number of peritraumatic emotional responses were concurrently associated with PTSD, only peritraumatic numbness maintained the association with this diagnosis longitudinally. For MDD, peritraumatic numbness was the only emotional response related to the diagnosis both concurrently and longitudinally. Study findings are a preliminary proof of concept that peritraumatic numbness may serve as a premorbid marker for the development of PTSD and MDD following a traumatic event. Implications of these findings for the diagnosis, assessment, and treatment of both PTSD and MDD are discussed.

The majority of research examining affective attentional bias in posttraumatic stress disorder (PTSD) has not examined the influence of co-occurring psychiatric disorders. This study examined the individual and interactive effects of PTSD symptoms and substance use disorders (SUDs) on affective attentional processing among 323 veterans deployed to Iraq or Afghanistan. Participants were divided into those with SUD (SUD+, n = 46) and those without (SUD-, n = 277). Substance use disorder was determined using the Structured Clinical Interview for DSM-IV. Posttraumatic stress disorder was measured using the Clinician Administered PTSD Scale. A computerized go/no-go task (Robbins et al., 1994, Robbins et al.,1998) assessed affective attentional processing. Relative to those without SUD, those with SUD showed a significant association between PTSD symptoms and increased omission and commission accuracy rates and decreased d prime. No effects of valence were found. Findings suggest the need to consider co-occurring SUD when investigating the effects of PTSD on attentional control.

Background: Posttraumatic stress disorder (PTSD) diagnostic criteria have been criticized for including symptoms that overlap with commonly comorbid disorders, which critics argue undermines the validity of the diagnosis and inflates psychiatric comorbidity rates. In response, the upcoming 11th edition of the International Classification of Diseases (ICD-11) will offer PTSD diagnostic criteria that are intended to promote diagnostic accuracy. However, diagnostic utility analyses have not yet assessed whether these criteria minimize diagnostic errors. The present study examined the diagnostic utility of each PTSD symptom in the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) for males and females., Methods: Participants were 1,347 individuals enrolled in a longitudinal national registry of returning veterans receiving care at a Department of Veterans Affairs (VA) facility. Doctoral level clinicians assessed all participants using the PTSD module of the Structured Clinical Interview for DSM., Results: Of the 20 symptoms examined, the majority performed in the fair to poor range on test quality indices. Although a few items did perform in the good (or better) range, only half were ICD-11 symptoms. None of the 20 symptoms demonstrated good quality of efficiency. Results demonstrated few sex differences across indices. There were no differences in the proportion of comorbid psychiatric disorders or functional impairment between DSM-5 and ICD-11 criteria., Conclusions: ICD-11 PTSD criteria demonstrate neither greater diagnostic specificity nor reduced rates of comorbidity relative to DSM-5 criteria and, as such, do not perform as intended. Modifications to existing symptoms or new symptoms may improve differential diagnosis., (© 2017 Wiley Periodicals, Inc.)

A high-throughput and robust application of the 3-methyl-2-benzothiazolinone hydrazone (MBTH) method was developed for carbohydrate determination in microalgae. The traditional phenol-sulfuric acid method to quantify carbohydrates is strongly affected by algal biochemical components and exhibits a highly variable response to microalgal monosaccharides. We present a novel use of the MBTH method to accurately quantify carbohydrates in hydrolyzate after acid hydrolysis of algal biomass, without a need for neutralization. The MBTH method demonstrated consistent and sensitive quantitation of algae-specific monosaccharides down to 5 μg mL -1 without interference from other algae acidic hydrolyzate components., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Although previous research has identified cognitive styles that distinguish individuals with bipolar disorder (BD), individuals with major depressive disorder (MDD), and individuals without mood disorders from one another, findings have been inconsistent. The current study included 381 participants classified into a BD group, a MDD group, and a no mood disorder group. To differentiate between these groups, this study evaluated cognitive styles with a battery of traditional and more recently-developed measures. Receiver operating characteristics (ROC) analyses were used to determine the discriminate ability of variables with significant between group differences. Results supported that BD and MDD may be characterized by distinct cognitive styles. Given work showing that interventions for MDD may not be effective at treating BD, it is important to directly compare individuals with these disorders. By clarifying the overlapping and divergent cognitive styles characterizing BD and MDD, research can not only improve diagnostic validity, but also provide more efficacious and effective interventions.

Research on life stress in bipolar disorder largely fails to account for the possibility of a dynamic relationship between psychosocial stress and episode initiation. The kindling hypothesis (Post, 1992) states that over the course of recurrent affective disorders, there is a weakening temporal relationship between major life stress and episode initiation that could reflect either a progressive sensitization or progressive autonomy to life stress. The present study involved a comprehensive and precise examination of the kindling hypothesis in 102 participants with bipolar II disorder that allowed for a direct comparison of sensitization and autonomy models. Polarity-specific tests were conducted across the continuum of event severity with respect to impact and frequency of life events. Hypotheses were polarity- and event-valence specific and were based on the stress sensitization model. Results were only partially consistent with the sensitization model: Individuals with more prior mood episodes had an increased frequency of minor negative events before depression and of minor positive events before hypomania. However, the number of past episodes did not moderate relationships between life events and time until prospective onset of mood episodes. These results are more consistent with a sensitization than an autonomy model, but several predictions of the sensitization model were not supported. Methodological strengths, limitations, and implications are discussed regarding putative changes in stress reactivity that may occur with repeated exposure to mood episodes in bipolar II disorder., ((PsycINFO Database Record (c) 2015 APA, all rights reserved).)

Objective: Stressful life events are associated with an increase in depressive symptoms and the onset of major depression. Importantly, research has shown that the role of stress changes over the course of depression. The present study extends the current literature by examining the effects of early life stress on emotional reactivity to current stressors., Method: In a multiwave study (N = 281, mean age = 18.76; 68% female), we investigated the proximal changes that occur in depressive symptoms when individuals are faced with life stress and whether a history of childhood emotional abuse moderates this relationship., Results: Results support the stress sensitivity hypothesis for early emotional abuse history. Individuals with greater childhood emotional abuse severity experienced greater increases in depressive symptoms when confronted with current dependent stressors, controlling for childhood physical and sexual abuse., Conclusions: This study highlights the importance of emotional abuse as an indicator for reactivity to stressful life events., (© 2013 Wiley Periodicals, Inc.)

To identify algal strains with altered starch metabolism from a large pool of candidates of growing algal colonies, we have developed a novel, high-throughput screening tool by combining gaseous bleaching of replica transferred colonies and subsequent iodine staining to visualize starch. Screening of healthy growing colonies of microalgae has not been possible previously because high levels of chlorophyll make the detection of starch with an iodine stain impossible. We demonstrated that chlorine dioxide (ClO(2)) removes essentially all chlorophyll from the colonies and enables high-throughput screening of, for example, a population of mutagenized cells or a culture collection isolated in a bioprospecting project., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Depressed young people may have sexual intercourse (sex) to regulate their disordered affective states. This study sought to determine how momentary positive and negative affect relate to subsequent sex events in depressed adolescents and young adults. Fifty-four outpatients (87% female) 15-22 years who reported clinically significant depressive symptoms and having sex at least once a week completed a baseline survey, then reported momentary affective states and the occurrence of sex events on a handheld computer in response to 4-6 random signals per day for 2 weeks. Participants identified 387 unique sex events (median, 3.5/participant/week) on 3,159 reports (median, signal response rate 80%). Most (86-96%) reported low burden of participation on questions asked at study completion. Similar to what has been reported in non-depressed young people, momentary positive and negative affect were both improved beginning approximately 6 h before until approximately 6 h after a sex event. Positive affect was lower in the 24 h before this pericoital period, compared to other times. Negative affect did not significantly differ between before the pericoital period and other times. The findings suggest that depressed youth may have sex to regulate their positive affect and have implications for provision of their mental and physical health care.

In the search for a replacement for fossil fuel and the valuable chemicals currently obtained from crude oil, lignocellulosic biomass has become a promising candidate as an alternative biorenewable source for crude oil. Hence, many research efforts focus on the extraction, degradation, and catalytic transformation of lignin, hemicellulose, and cellulose. Unfortunately, these processes result in the production of very complex mixtures. Further, while methods have been developed for the analysis of mixtures of oligosaccharides, this is not true for the complex mixtures generated upon degradation of lignin. For example, high-performance liquid chromatography/multiple stage tandem mass spectrometry (HPLC/MS(n)), a tool proven to be invaluable in the analysis of complex mixtures derived from many other biopolymers, such as proteins and DNA, has not been implemented for lignin degradation products. In this study, we have developed an HPLC separation method for lignin degradation products that is amenable to negative-ion-mode electrospray ionization (ESI doped with NaOH), the best method identified thus far for ionization of lignin-related model compounds without fragmentation. The separated and ionized compounds are then analyzed by MS(3) experiments to obtain detailed structural information while simultaneously performing high-resolution measurements to determine their elemental compositions in the two parts of a commercial linear quadrupole ion trap/Fourier-transform ion cyclotron resonance mass spectrometer. A lignin degradation product mixture was analyzed using this method, and molecular structures were proposed for some components. This methodology significantly improves the ability to analyze complex product mixtures that result from degraded lignin.

We examined the concurrent associations between multiple cognitive vulnerabilities to depression featured in hopelessness theory, Beck's theory, and response styles theory and depressive symptoms and diagnoses in a sample of early adolescents. We also examined the specificity of these cognitive vulnerabilities to depression versus anxiety and externalizing psychopathology, controlling for co-occurring symptoms and diagnoses. Male and female, Caucasian and African American, 12- to 13-year-old adolescents were assessed in a cross-sectional design. Cognitive vulnerabilities of hopelessness, inferential style, rumination, and self-referent information processing were assessed with self-reports and behavioral tasks. Symptoms and diagnoses of depressive, anxiety, and externalizing disorders were assessed with self-report questionnaires and diagnostic interviews. Hopelessness exhibited the greatest specificity to depressive symptoms and diagnoses, whereas negative inferential styles, rumination, and negative self-referent information processing were associated with both depressive and anxiety symptoms and diagnoses and, in some cases, with externalizing disorders. Consistent with cognitive theories of depression, hopelessness, negative inferential styles, rumination, and negative self-referent information processing were associated with depressive symptoms and diagnoses. However, with the exception of hopelessness, most of the remaining cognitive vulnerabilities were not specific to depression. With further maturation of our sample, these cognitive vulnerabilities may become more specific to depression as cognitive styles further develop and consolidate, the rates of depression increase, and individuals' presentations of psychopathology become more differentiated.