COVID-19 and obsessive-compulsive symptoms in a large multi-site college sample.

The COVID-19 pandemic poses unique risks to college students' mental health, and specifically to symptoms of obsessive-compulsive disorder (OCD). To better understand the relationship between COVID-19 impact and OC symptoms in this population, six colleges from across the US administered a battery of questionnaires and an emotion differentiation paradigm to eligible students (N = 841). We examined whether degree of pandemic-related disruption was associated with OC severity, and if so, whether this relationship was explained by trait (poor emotion regulation and differentiation) and state risk factors (poor sleep quality, less exercise frequency, less social support, thwarted sense of belongingness, and greater loneliness). Results indicated that the positive relationship between COVID-19 impact and OC severity was mediated by trait emotion-related processes (e.g., emotion regulation and differentiation), but no state risk factors emerged as significant mediators. Our findings contribute to the literature demonstrating a significant relationship between COVID-19 impact and OC severity, and highlight that emotion regulation difficulties may help explain this association. Our findings can inform evidence-based interventions on college campuses; however, the cross-sectional design precludes causal inferences. Future research should evaluate these relationships longitudinally and incorporate other psychosocial factors that may operate as mechanisms.

A multi-method examination of the link between obsessive-compulsive symptomatology and emotion-related impulsivity.

OBJECTIVES: Obsessive-compulsive disorder (OCD) is a condition marked by recurrent and distressing thoughts, images, and urges accompanied by repetitive physical or mental rituals. An emerging line of work suggests that emotion may be an important consideration when looking at the role of impulsivity across the spectrum of psychopathology, including OCD. The current study examined the relationship between obsessive-compulsive symptomatology (OCS) and impulsive cognitive and behavioural reactions to emotion using a multi-study, multi-method approach. DESIGN: Data were collected cross-sectionally online (Study 1) or via an in-person laboratory visit (Study 2). METHODS: In Study 1, self-report measures of impulsivity and OCS were administered to a large, non-selected community sample (N = 386). Study 2 extended these findings with a young adult sample (N = 107) with clinically elevated OCS using self-report measures, clinical interview, and two behavioural symptom provocation tasks. RESULTS: Emotion-related impulsivity, but not non-emotion-related impulsivity, was associated with greater severity of OCS across symptom domains and across all modes of assessment. Impulsive cognitive responses to emotion were associated with greater obsession severity, while impulsive behavioural reactions to emotion were associated with greater compulsions. Emotion-related impulsivity also acted synergistically with a belief in the importance and control of thoughts, such that this established risk factor for OCD was associated with greater OCS severity only when behavioural reactivity to emotion was also present. CONCLUSIONS: Results highlight the importance of considering emotional context when studying impulsivity in OCD, and point to the potentially differential relationship between OCS and behavioural versus cognitive impulsive reactions to emotion. PRACTITIONER POINTS: Emotion-related impulsivity (ERI) reflects a tendency to act impulsively in the context of strong emotions. ERI was associated with greater OCS across symptom domains and type of symptom assessment (self-report, interview, or symptom provocation). ERI also interacted with an established OCS risk factor, a belief in the importance and control of thoughts, to predict symptom severity, suggesting that it may be important to evaluate and address ERI alongside unhelpful beliefs in patients with OCS. Given the present study's cross-sectional nature, we cannot draw conclusions about the directionality of the ERI - OCS relationship, and while our study included individuals with clinically elevated OCS, results should be replicated in a fully clinical sample.

Feasibility and acceptability of an online mindfulness-based group intervention for adults with tic disorders.

BACKGROUND: Preliminary research suggests that a mindfulness-based treatment approach may be beneficial for adults with tic disorders. In the present study, we report on the feasibility, acceptability, safety, and symptomatic effect of a novel online mindfulness-based group intervention for adults with Tourette syndrome or persistent tic disorder. Data from this study will directly inform the conduct of a funded randomized controlled trial comparing the efficacy of this intervention to another active psychological intervention. METHODS: One cohort of adults with Tourette syndrome participated in an 8-week online mindfulness-based group intervention. Measures of feasibility, acceptability, and safety were administered throughout and at posttreatment. Self-reported measures of mindfulness and clinician-rated measures of tic severity and impairment were administered at baseline and posttreatment. RESULTS: Data on refusal, dropout rate, attendance, participant satisfaction, and safety suggest that this is a feasible and acceptable intervention. However, participant adherence to home practice was lower than anticipated. Mindfulness, tic severity, and tic-related impairment only modestly improved from baseline to posttreatment. Qualitative analysis of participant feedback revealed aspects of the intervention that were most helpful and also areas for improvement. CONCLUSIONS: Data suggest that although this is a feasible and acceptable intervention, it should be modified to enhance participant adherence, more successfully engage the target mechanism, and optimize outcomes. TRIAL REGISTRATION: Clinicaltrials.gov registration # NCT03525626 . Registered on 24 April 2018.

Use of Target-Displaying Magnetized Yeast in Screening mRNA-Display Peptide Libraries to Identify Ligands.

This work presents the first use of yeast-displayed protein targets for screening mRNA-display libraries of cyclic and linear peptides. The WW domains of Yes-Associated Protein 1 (WW-YAP) and mitochondrial import receptor subunit TOM22 were adopted as protein targets. Yeast cells displaying WW-YAP or TOM22 were magnetized with iron oxide nanoparticles to enable the isolation of target-binding mRNA-peptide fusions. Equilibrium adsorption studies were conducted to estimate the binding affinity (KD) of select WW-YAP-binding peptides: KD values of 37 and 4 µM were obtained for cyclo[M-AFRLC-K] and its linear cognate, and 40 and 3 µM for cyclo[M-LDFVNHRSRG-K] and its linear cognate, respectively. TOM22-binding peptide cyclo[M-PELNRAI-K] was conjugated to magnetic beads and incubated with yeast cells expressing TOM22 and luciferase. A luciferase-based assay showed a 4.5-fold higher binding of TOM22+ yeast compared to control cells. This work demonstrates that integrating mRNA- and yeast-display accelerates the discovery of peptide ligands.

Novel peptide ligands for antibody purification provide superior clearance of host cell protein impurities.

The quest for ligands alternative to Protein A for the purification of monoclonal antibodies (mAbs) has been pursued for almost three decades. Yet, the IgG-binding peptides known to date still fall short of the host cell protein (HCP) logarithmic removal value (LRV) set by Protein A media (2.5-3.1). In this study, we present an integrated computational-experimental approach leading to the discovery of peptide ligands that provide HCP LRVs on par with Protein A. First, the screening of 60,000 peptide variants was performed using a high-throughput search algorithm to identify sequences that ensure IgG affinity binding. Select sequences WQRHGI, MWRGWQ, RHLGWF, and GWLHQR were then negatively screened in silico against a panel of model HCPs to ensure the selection of peptides with high binding selectivity. Candidate ligands WQRHGI and MWRGWQ were conjugated to chromatographic resins and characterized by isothermal binding and breakthrough assays to quantify static and dynamic binding capacity (Qmax and DBC10%), respectively. The resulting Qmax were 52.6 mg of IgG per mL of adsorbent for WQRHGI and 57.48 mg/mL for MWRGWQ, while the DBC10% (2 minutes residence time) were 30.1 mg/mL for WQRHGI and 36.4 mg/mL for MWRGWQ. Evaluation of the peptides by isothermal titration calorimetry (ITC) confirmed the binding energy predicted in silico, and an amino acid scanning study corroborated the affinity-like binding activity of the peptides. WQRHGI-WorkBeads resin was finally characterized by purification of a monoclonal antibody from a Chinese Hamster Ovary (CHO) cell culture harvest, affording a remarkable HCP LRV of 2.7, and consistent product yield and purity over 100 chromatographic cycles. These results demonstrate the potential of WQRHGI as an effective alternative to Protein A for antibody purification.

Purification of animal immunoglobulin G (IgG) using peptoid affinity ligands.

The availability of highly pure animal antibodies is critical in the production of diagnostic tools and biosensors. The peptoid PL16, previously isolated from an ensemble of peptoid variants of the IgG-binding peptide HWRGWV, was utilized in this work as affinity ligand on WorkBeads resin for the purification of immunoglobulin G (IgG) from a variety of mammalian sources and chicken immunoglobulin Y (IgY). The chromatographic protocol initially optimized for murine serum and ascites was subsequently employed for processing rabbit, goat and sheep, donkey, llama, and chicken sera. The PL16-WorkBeads resin proved able to recover all antibody targets with values of yield between 50 and 90%, and purity consistently above 90%. Notably, PL16 not only binds a broader spectrum of animal immunoglobulins than the reference ligands Protein A and G, but it also binds equally well with all their subclasses. Unlike the protein ligands, in fact, PL16 afforded excellent values of yield and purity of mammalian polyclonal IgG, namely murine (47 and 94%), rabbit (66.5 and 91.7%), caprine IgG (63 and 91-95%), donkey, and llama (93 and 97%), as well as chicken IgY (42 and 92%). Of notice, it is also the ability of PL16 to target monomeric IgG without binding aggregated IgG; when challenged with a mixture of monomeric and aggregated murine IgG, PL16 eluted <3% of fed aggregates, against 11-13% eluted by Protein A and G. Collectively, these results prove the potential of the proposed peptoid ligand for large-scale purification of animal immunoglobulins.

Investigating the Role of Interpretation Bias in Mindfulness-Based Treatment of Adults With Generalized Anxiety Disorder.

Although mindfulness-based interventions (MBIs) have garnered empirical support for a wide range of psychological conditions, the psychological processes that mediate the relationship between MBIs and subsequent symptomatic improvement are less well-understood. In the present study we sought to examine, for the first time, the relationship between mindfulness, negative interpretation bias as measured by the homophone task, and anxiety among adults with Generalized Anxiety Disorder (GAD). Forty-two individuals with GAD completed measures of mindfulness, interpretation bias, and anxiety before and after treatment with Mindfulness-based Stress Reduction (MBSR). Contrary to prior research, we did not find evidence of an indirect relationship between baseline levels of mindfulness and anxiety via negative interpretation bias. MBSR did result in significant reductions in negative interpretation bias from baseline to post-treatment; however, we did not find evidence of an indirect relationship between changes in mindfulness and changes in anxiety via changes in interpretation bias. Taken together, these results provide minimal support for the hypothesized relationship between mindfulness, negative interpretation bias, and anxiety among adults with GAD. Limitations and specific suggestions for further inquiry are discussed.

Peptide science: A "rule model" for new generations of peptidomimetics.

Peptides have been heavily investigated for their biocompatible and bioactive properties. Though a wide array of functionalities can be introduced by varying the amino acid sequence or by structural constraints, properties such as proteolytic stability, catalytic activity, and phase behavior in solution are difficult or impossible to impart upon naturally occurring α-L-peptides. To this end, sequence-controlled peptidomimetics exhibit new folds, morphologies, and chemical modifications that create new structures and functions. The study of these new classes of polymers, especially α-peptoids, has been highly influenced by the analysis, computational, and design techniques developed for peptides. This review examines techniques to determine primary, secondary, and tertiary structure of peptides, and how they have been adapted to investigate peptoid structure. Computational models developed for peptides have been modified to predict the morphologies of peptoids and have increased in accuracy in recent years. The combination of in vitro and in silico techniques have led to secondary and tertiary structure design principles that mirror those for peptides. We then examine several important developments in peptoid applications inspired by peptides such as pharmaceuticals, catalysis, and protein-binding. A brief survey of alternative backbone structures and research investigating these peptidomimetics shows how the advancement of peptide and peptoid science has influenced the growth of numerous fields of study. As peptide, peptoid, and other peptidomimetic studies continue to advance, we will expect to see higher throughput structural analyses, greater computational accuracy and functionality, and wider application space that can improve human health, solve environmental challenges, and meet industrial needs. STATEMENT OF SIGNIFICANCE: Many historical, chemical, and functional relations draw a thread connecting peptides to their recent cognates, the "peptidomimetics". This review presents a comprehensive survey of this field by highlighting the width and relevance of these familial connections. In the first section, we examine the experimental and computational techniques originally developed for peptides and their morphing into a broader analytical and predictive toolbox. The second section presents an excursus of the structures and properties of prominent peptidomimetics, and how the expansion of the chemical and structural diversity has returned new exciting properties. The third section presents an overview of technological applications and new families of peptidomimetics. As the field grows, new compounds emerge with clear potential in medicine and advanced manufacturing.

Novel peptoid-based adsorbents for purifying IgM and IgG from polyclonal and recombinant sources.

Polyclonal immunoglobulin therapeutics comprising dosed IgG and IgM combinations are powerful tools in fighting cancer and severe infections. The inability of protein ligands to produce polyclonal IgG- and IgM-enriched formulations and recover monoclonal IgM calls for novel ligands with superior biorecognition activity. In this study, a peptoid ligand discovered by our group, and integrated into affinity adsorbents LigaTrap Technologies' "Human IgG" and "Human IgM", were utilized to purify IgG and IgM from complex fluids. IgG purification from human serum using LigaTrap IgG afforded 94.6% purity and 62.9% yield, on par with Protein A/G resins. When challenged with CHO and HEK cell culture harvests with low IgG titer (<1 mg/mL), LigaTrap IgG returned values of yield and purity well above 60% and 90%. LigaTrap IgM was evaluated for purifying IgM in comparison with commercial adsorbents, and afforded a product purity of 93% from a CHO harvest (IgM titer of 1 mg/mL) and 75.1% yield from a HEK harvest (0.5 mg/mL). LigaTrap-M provided IgM enrichment up to 11-fold higher than HiTrap resin. The peptoid adsorbents separated IgG-depleted human serum into IgM- and IgA-enriched fractions. These results demonstrate the potential of the peptoid ligand for manufacturing polyclonal Ig formulations and monoclonal IgM therapeutics.

Chromatographic assay to probe the binding energy and mechanisms of homologous proteins to surface-bound ligands.

Probing the affinity of a ligand for homologous protein targets currently relies on laborious assays that need special equipment and high amounts of isolated, highly pure proteins. Herein we present the use of pISep, an integrated buffer system and modeling package, as an analytical method to rapidly and accurately probe the binding strength and mechanisms of homologous proteins to surface-bound ligands. To demonstrate our method, we utilized the four subclasses of human immunoglobulin G (IgG) as model homologous protein targets and the IgG-binding peptide HWRGWV as model ligand. Following IgG adsorption on a HWRGWV-Toyopearl adsorbent, the pISep buffer system was used to run uncoupled dual elution gradients of pH (from pH 8.5 to 2.5) and either isocratic or time dependent salt concentration. Both the sequence and partial overlap of elution times (IgG4 > IgG3 ≥ IgG1 > IgG2) was found to match closely the values of binding strength (KD) determined with both in silico docking simulations and isothermal titration calorimetry experiments. pISep gradients performed at different values of ionic strengths provided a means to compare the contribution of hydrophobic vs. electrostatic interactions to the IgG-peptide affinity. The shifts in retention times indicated that, among the various components of the binding energy, the hydrophobic interaction dominates in the binding of IgG2 and IgG4, whereas the binding of IgG1 and IgG3 features a balance of electrostatic and hydrophobic modes. These findings were also confirmed by the in silico analysis of the complexes formed by HWRGWV and the Fc fragment of the IgG subclasses. Collectively, these results indicate that the retention times on pISep elution gradients - in particular peak max, overlap, and shift under different conditions - directly correlate to the strength and nature of protein-ligand interactions. This work demonstrates the effectiveness of the pISep toolbox for probing the differential binding of homologous proteins to a reference ligand and informing the optimization of platform processes for the purification and fractionation of biotherapeutics.

Translating antibody-binding peptides into peptoid ligands with improved affinity and stability.

A great number of protein-binding peptides are known and utilized as drugs, diagnostic reagents, and affinity ligands. Recently, however, peptide mimetics have been proposed as valuable alternative to peptides by virtue of their excellent biorecognition activity and higher biochemical stability. This poses the need to develop a strategy for translating known protein-binding peptides into peptoid analogues with comparable or better affinity. This work proposes a route for translation utilizing the IgG-binding peptide HWRGWV as reference sequence. An ensemble of peptoid analogues of HWRGWV were produced by adjusting the number and sequence arrangement of residues containing functional groups that resemble both natural and non-natural amino acids. The variants were initially screened via IgG binding tests in non-competitive mode to select candidate ligands. A set of selected peptoids were studied in silico by docking onto putative binding sites identified on the crystal structures of human IgG1, IgG2, IgG3, and IgG4 subclasses, returning values of predicted binding energy that aligned well with the binding data. Selected peptoids PL-16 and PL-22 were further characterized by binding isotherm analysis to determine maximum capacity (Qmax ˜ 48-57 mg of IgG per mL of adsorbent) and binding strength on solid phase (KD ˜ 5.4-7.8 10-7 M). Adsorbents PL-16-Workbeads and PL-22-Workbeads were used for purifying human IgG from a cell culture supernatant added with bovine serum, affording high values of IgG recovery (up to 85%) and purity (up to 98%) under optimized binding and elution conditions. Both peptoid ligands also proved to be stable against proteolytic enzymes and strong alkaline agents. Collectively, these studies form a method guiding the design of peptoid variants of cognate peptide ligands, and help addressing the challenges that, despite the structural similarity, the peptide-to-peptoid translation presents.

Neurocognitive predictors of treatment response to randomized treatment in adults with tic disorders.

Tourette's disorder (TS) and chronic tic disorder (CTD) are neurodevelopmental disorders characterized by involuntary vocal and motor tics. Consequently, TS/CTD have been conceptualized as disorders of cognitive and motor inhibitory control. However, most neurocognitive studies have found comparable or superior inhibitory capacity among individuals with TS/CTD relative to healthy controls. These findings have led to the hypothesis that individuals with TS/CTD develop increased inhibitory control due to the constant need to inhibit tics. However, the role of cognitive control in TS/CTD is not yet understood, particularly in adults. To examine the role of inhibitory control in TS/CTD, the present study investigated this association by assessing the relationship between inhibitory control and treatment response in a large sample of adults with TS/CTD. As part of a large randomized trial comparing behavior therapy versus supportive psychotherapy for TS/CTD, a battery of tests, including tests of inhibitory control was administered to 122 adults with TS/CTD at baseline. We assessed the association between neuropsychological test performance and change in symptom severity, as well as compared the performance of treatment responders and non-responders as defined by the Clinical Global Impression Scale. Results indicated that change in symptoms, and treatment response were not associated with neuropsychological performance on tests of inhibitory control, intellectual ability, or motor function, regardless of type of treatment. The finding that significant change in symptom severity of TS/CTD patients is not associated with impairment or change in inhibitory control regardless of treatment type suggests that inhibitory control may not be a clinically relevant facet of these disorders in adults.

Psychometric Properties of a Self-Report Instrument for the Assessment of Tic Severity in Adults With Tic Disorders.

The gold-standard measure of tic severity in tic disorders (TD), the Yale Global Tic Severity Scale (YGTSS), is a semistructured clinician-administered interview that can be time consuming and requires highly trained interviewers. Moreover, the YGTSS does not provide information regarding frequency and intensity of specific tics because all motor and all vocal tics are rated as a group. The aim of the present study is to describe and test the Adult Tic Questionnaire (ATQ), a measure for the assessment of tic severity in adults, and to report its preliminary psychometric properties. The ATQ is a brief self-report questionnaire that provides information regarding frequency, intensity, and severity of 27 specific tics. In addition, the ATQ produces total frequency, intensity, and severity scores for vocal and motor tics, as well as a global total tic severity score. Results showed that the ATQ demonstrated very good internal consistency and temporal stability. The total, vocal, and motor tic severity scales of the ATQ showed strong correlation with corresponding subscales of the YGTSS, indicating strong convergent validity. Weak correlations with measures of severity of obsessive-compulsive disorder and attention deficit/hyperactivity disorder, indicated strong discriminant validity. The ATQ, a promising measure for the assessment of tic severity in adults with TD, may be a valuable supplement to the current recommended assessment battery for TD. Furthermore, the ATQ enables clinicians and researchers to track changes in the frequency and intensity of specific tics, which is important given their complex and dynamic nature.

Getting the word out: cognitive-behavioral therapy for trichotillomania (hair-pulling disorder) and excoriation (skin-picking) disorder.

BACKGROUND: To date, there has been no investigation of dissemination outcomes for cognitive-behavioral training programs for body-focused repetitive behaviors (BFRBs). METHODS: Sixty-three past participants of the Trichotillomania Learning Center (TLC) intensive professional training institutes completed an online survey assessing referral sources, skills utilization, and treatment outcomes before and after training. The intensive training focused on the treatment of trichotillomania (hair-pulling) disorder and excoriation (skin-picking) disorder using in-person or videotaped didactics, role playing, and case presentations with supervision upon request. RESULTS: Participants endorsed a greater number of referral sources and BFRB patients after attending training. Paired t tests indicated significant pre- to post-training increases in self-reported utilization of all individual cognitive-behavioral therapy (CBT) skills as well as overall mean skills usage (both P<.001). Changes after training in the reported percent of abstinent patients and mean reduction in symptom severity were also noted. CONCLUSIONS: The TLC intensive professional training institutes may be useful for disseminating CBT skills for the treatment of BFRBs, but additional research is warranted.

Mindfulness-based stress reduction for Tourette Syndrome and Chronic Tic Disorder: a pilot study.

OBJECTIVE: In this pilot study we sought to develop and test a modified form of mindfulness-based stress reduction (MBSR-tics) for the treatment of Tourette Syndrome (TS) and Chronic Tic Disorder (CTD). Our specific aims were: 1) To determine the feasibility and acceptability of an 8-week trial of MBSR-tics in individuals 16 and older with TS or CTD and 2) To determine the efficacy of an 8-week trial of MBSR-tics in individuals 16 and older with TS or CTD. METHODS: Eighteen individuals age 16-67 completed an uncontrolled open trial of MBSR-tics. The intervention consisted of 8 weekly 2-hour classes and one 4hour retreat in the fifth or sixth week of the program. Symptomatic assessments were performed at baseline, post-treatment, and one-month follow-up. RESULTS: MBSR-tics proved to be a feasible and acceptable intervention. It resulted in significant improvement in tic severity and tic-related impairment. 58.8% of subjects were deemed treatment responders. Therapeutic gains were maintained at 1-month follow-up. Improvements in tic severity were correlated with increases in self-reported levels of mindfulness. CONCLUSIONS: This small open pilot study provides preliminary support for the feasibility, acceptability, and efficacy of MBSR-tics for individuals 16 or older with TS or CTD. A larger randomized controlled trial with blind assessment is necessary to confirm these initial, promising findings. Trial Registration Partners Clinical Trials Registry Number 2011P000606 (clinicaltrials.partners.org).

Neural correlates of behavior therapy for Tourette's disorder.

Tourette's disorder, also called Tourette syndrome (TS), is characterized by motor and vocal tics that can cause significant impairment in daily functioning. Tics are believed to be due to failed inhibition of both associative and motor cortico-striato-thalamo-cortical pathways. Comprehensive Behavioral Intervention for Tics (CBIT), which is an extension of Habit Reversal Therapy (HRT), teaches patients to become more aware of sensations that reliably precede tics (premonitory urges) and to initiate competing movements that inhibit the occurrence of tics. In this study, we used functional magnetic resonance imaging (fMRI) to investigate the neural changes associated with CBIT treatment in subjects with TS. Eight subjects with TS were matched with eight healthy controls in gender, education, age, and handedness. Subjects completed the Visuospatial Priming (VSP) task, a measure of response inhibition, during fMRI scanning before and after CBIT treatment (or waiting period for controls). For TS subjects, we found a significant decrease in striatal (putamen) activation from pre- to post-treatment. Change in VSP task-related activation from pre- to post-treatment in Brodmann's area 47 (the inferior frontal gyrus) was negatively correlated with changes in tic severity. CBIT may promote normalization of aberrant cortico-striato-thalamo-cortical associative and motor pathways in individuals with TS.

The premonitory urge to tic: measurement, characteristics, and correlates in older adolescents and adults.

In addition to motor and/or vocal tics, many individuals with Tourette syndrome (TS) or chronic tic disorder (CTD) report frequent, uncomfortable sensory phenomena that immediately precede the tics. To date, examination of these premonitory sensations or urges has been limited by inconsistent assessment tools. In this paper, we examine the psychometric properties of a nine-item self-report measure, the Premonitory Urge to Tic Scale (PUTS) and examine the characteristics and correlates of the premonitory urge to tic in a clinical sample of 122 older adolescents and adults with TS or CTD. The PUTS demonstrated adequate internal consistency, temporal stability, and concurrent validity. Premonitory urges were endorsed by the majority of individuals. Most individuals reported some relief from the urges after completing a tic and being able to stop their tics even if only temporarily. Degree of premonitory urges was not significantly correlated with age, and we did not observe any gender differences. Degree of premonitory urges was significantly correlated with estimated IQ and tic severity, but not severity of comorbid obsessive-compulsive disorder or attention-deficit hyperactivity disorder. Also, it was not related to concomitant medication status. These findings represent another step forward in our understanding of the premonitory sensations associated with TS and CTD.

Reflections on the theory-practice gap in cognitive behavior therapy.

The papers in this special series, edited by Pilecki and McKay (2013--this issue), are devoted to examining the theory-practice gap in cognitive-behavior therapy (CBT). A gap between theory and practice can occur at more than one level. First, there exists a substantial and concerning gap between the theories and interventions supported by research and those being offered to patients in the community (i.e., research-practice gap). There is also a growing concern in the field that the techniques and procedures that characterize cognitive-behavioral therapies are becoming increasingly divorced from underlying theories (i.e., theory-procedure gap). In the present commentary we hope to summarize and comment on some of the themes, issues, and future directions raised by our contributors.

Process for purification of monoclonal antibody expressed in transgenic Lemna plant extract using dextran-coated charcoal and hexamer peptide affinity resin.

The production of therapeutic proteins using transgenic plants offers several advantages, including low production cost, absence of human pathogens, presence of glycosylation mechanisms, and the ability to fold complex therapeutic proteins into their proper conformation. However, impurities such as phenolic compounds and pigments encountered during purification are quite different from those faced during purification from mammalian cell culture supernatants. This paper deals with the development of a pretreatment and affinity separation process for the purification of a monoclonal antibody from transgenic Lemna plant extract. A pretreatment step is described using dextran-coated charcoal for the removal of pigments and phenolic compounds without reducing the antibody concentration. Then, the peptide affinity ligand HWRGWV coupled to a commercial polymethacrylate resin is used for the capture and purification of MAb from the pretreated plant extract. The final yield and purity of the MAb obtained were 90% and 96% respectively. The performance of the hexamer peptide resin after the pretreatment step was found to be similar to that obtained with a commercial Protein A resin.

Attention training toward and away from threat in social phobia: effects on subjective, behavioral, and physiological measures of anxiety.

Social phobics exhibit an attentional bias for threat in probe detection and probe discrimination paradigms. Attention training programs, in which probes always replace nonthreatening cues, reduce attentional bias for threat and self-reported social anxiety. However, researchers have seldom included behavioral measures of anxiety reduction, and have never taken physiological measures of anxiety reduction. In the present study, we trained individuals with generalized social phobia (n = 57) to attend to threat cues (attend to threat), to attend to positive cues (attend to positive), or to alternately attend to both (control condition). We assessed not only self-reported social anxiety, but also behavioral and physiological measures of social anxiety. Participants trained to attend to nonthreatening cues demonstrated significantly greater reductions in self-reported, behavioral, and physiological measures of anxiety than did participants from the attend to threat and control conditions.