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Lyme disease, caused by Borrelia burgdorferi sensu stricto and most commonly transmitted by Ixodes scapularis Say (Ixodida: Ixodidae), is the most common tick-borne disease in Maryland. Because B. burgdorferi s.s. is maintained in enzootic cycles among wild mice (Peromyscus spp) and Ixodes spp ticks, differing patterns of parasitism of ticks on mice could impact the infection prevalence with B. burgdorferi. We determined the infection prevalence of Peromyscus spp as well as questing and partially engorged nymphal ticks collected at six sites on private land in five counties in Maryland from May to August 2020. Questing nymph infection prevalence (NIP) was 14%. We trapped 1258 mice and collected 554 ticks and 413 ear tissue samples. The prevalence of infested Peromyscus spp varied based on host age and sex, with older and male mice more likely to be infested. We detected a significant difference amongst the proportion of attached Ixodes and the location of trapping. Similarly, the prevalence of B. burgdorferi infected Peromyscus spp mice varied between locations (average mouse infection prevalence was 40%), with the highest prevalence in locations where Ixodes were the most commonly found ticks. The B. burgdorferi infection prevalence in partially engorged I. scapularis nymphs retrieved from Peromyscus spp was ~36% which lends further support to the host infection prevalence. Local differences in distribution of infected vectors and reservoirs are important factors to consider when planning interventions to reduce Lyme disease risk.

Objective This article examined associations between change in youth and family characteristics during youth anxiety treatment and long-term anxiety severity and overall functioning. Method Participants (N = 488; age 7-17 years; 45% male; 82% white) were randomized to 12 weeks of cognitive behavioral therapy (Coping Cat), medication (sertraline), their combination, or pill placebo in the Child/Adolescent Anxiety Multimodal Study (CAMS). A subset participated in the naturalistic follow-up Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS; n = 319; 3.70-11.83 years post-treatment). The current secondary analyses examined how change in anxiety severity (Child Global Impression-Severity), overall functioning (Children's Global Assessment Scale), caregiver psychopathology (Brief Symptom Inventory), caregiver strain (Family Burden Assessment Scale), and family dysfunction (Brief Family Assessment Measure) during CAMS was associated with anxiety severity and overall functioning years later (M = 7.72 years). CAMS procedures were registered on clinialtrials.gov. Results Improvements in factors related to functioning (i.e., overall functioning, family dysfunction, caregiver strain) were associated with improvements in anxiety severity in CAMELS (|βys| ≥ .04, ps ≤ .04). Improvements in factors related to psychopathology (i.e., anxiety severity, caregiver psychopathology) were associated with improvements in overall functioning in CAMELS (|βys| ≥ .23, ps ≤ .04). It was changes in each of the variables examined (rather than baseline values) that predicted anxiety severity and overall functioning. Conclusions Both youth and family factors play a significant role in long-term treatment outcomes. Therapists would be wise to monitor how these factors change throughout treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Working memory (WM) develops rapidly during early childhood. In the present study, visual WM (VSM) was measured using the well-established Spin the Pots task (Hughes & Ensor, 2005), a complex non-verbal eight-location object occlusion task. A self-ordered hiding procedure was adopted to allow for an examination of children's strategy use during a VWM task. Participants (N = 640) between the ages of 2 and 4 years were tested under semi-naturalistic conditions, in the home or in a museum. Computational modeling was used to estimate an expected value for the total trials to complete Spin the Pots via a random search and child performance was compared to expected values. Based on this approach, we determined that children who found six stickers retrieved them in significantly fewer trials than the expected value, excluding chance performance and implicating VWM. Results also showed age-related and sex-related changes in VWM. Between 2 and 4 years of age, 4-year-olds performed significantly better than younger children and girls out-performed the boys. Spontaneous use of a color matching hiding strategy was associated with a higher success rate on the task. Implications of these findings for early development of VWM are discussed.

OBJECTIVE: Accommodation, or the ways in which families modify their routines and expectations in response to a child’s anxiety, is common and interferes with anxiety treatment outcomes. However, little research has examined family accommodation among youth with autism spectrum disorder and anxiety. The current study aimed to (a) identify pre-treatment correlates of accommodation, (b) examine changes in accommodation after treatment, and (c) assess relationships between accommodation and post-treatment anxiety severity. METHOD: The sample consisted of 167 youth (mean age=9.90 years; 79.6% male; 18% Latinx) with clinically significant anxiety and a diagnosis of autism spectrum disorder who were enrolled in a randomized clinical trial comparing two cognitive behavioral therapy interventions for anxiety and treatment as usual. Participants were evaluated for symptom severity and family accommodation at pre- and post-treatment. RESULTS: Results indicated that clinician-rated anxiety severity and parent-rated externalizing behaviors and autism spectrum disorder severity significantly predicted pre-treatment accommodation. Accommodation significantly decreased from pre- to post-treatment and non-responders showed significantly higher accommodation at post-treatment compared to responders. Finally, youth with higher pre-treatment accommodation had higher post-treatment anxiety. CONCLUSIONS: Findings indicate that accommodation for anxiety is common among youth with autism spectrum disorder and anxiety. Furthermore, accommodation is implicated in treatment outcomes and should be targeted in treatment for youth with autism spectrum disorder and anxiety.

BACKGROUND: Current approaches to increasing the rates of clinician use of exposure therapy for anxiety disorders in community settings are limited. Research underscores the importance of addressing contextual variables to facilitate clinician use of evidence-based practices; however, no studies have identified the innovation-specific organizational capacity necessary to implement exposure therapy. Such work is critical to ensure that treatment-seeking individuals with anxiety receive effective care. METHODS: We used a two-step process to identify the innovation-specific organizational capacity necessary to deliver exposure. First, 24 leaders of specialty anxiety clinics in the United States (50% female, mean [M]age = 47.7 years) completed a survey about the organizational innovation-specific capacity (e.g., policies and procedures) they employ to support their providers in delivering exposure therapy. Second, 19 community clinicians (79% female, M age = 42.9 years) reported on the extent to which these characteristics were present in their settings. RESULTS: In Step 1, specialty clinic leaders unanimously endorsed six organizational characteristics as essential and five as important within the areas of organizational policies, supervisory support, and peer clinician support. These characteristics were present in more than 90% of specialty clinics. In Step 2, therapists in community clinics reported these characteristics were minimally present in their organizations. CONCLUSIONS: Specialty clinic leaders exhibited consensus on the innovation-specific organizational capacity necessary to implement exposure therapy. Identified characteristics were largely absent from community clinics. Developing fiscal, policy, or organizational strategies that enhance the organizational capacity within community settings may improve the patients’ access to effective treatment for anxiety disorders.

The current study explored whether patient characteristics predicted patterns of antidepressant use (i.e., never used, single episode of use, or two or more episodes) in a naturalistic follow-up. Participants in the child/adolescent multimodal (CAMS) extended long-term study. (n = 318) indicated medication use over the course of eight follow-up visits, 3-12 years after receiving treatment in CAMS. 40.6% of participants reported never using an antidepressant during follow-up, 41.4% reported a single episode of antidepressant use, and 18.0% reported multiple episodes of antidepressant use. Greater baseline anxiety severity marginally predicted a single episode of antidepressant use; baseline depression severity predicted multiple episodes of use. Reasons for discontinuing antidepressants included perceived ineffectiveness (31.8%), side effects (25.5%), and improvement in symptoms (18.5%). Exploratory analyses examined predictors of medication use. Findings suggest that antidepressant use is common among anxious youth, as is discontinuation of antidepressant use. Clinical implications and future directions are discussed.

The hippocampus contributes to both remembering specific events and generalization across events. Recent work suggests that information may be represented along the longitudinal axis of the hippocampus at varied levels of specificity: detailed representations in the posterior hippocampus and generalized representations in the anterior hippocampus. Similar distinctions are thought to exist within neocortex, with lateral prefrontal and lateral parietal regions supporting memory specificity and ventromedial prefrontal and lateral temporal cortices supporting generalized memory. Here, we tested whether functional connectivity of anterior and posterior hippocampus with cortical memory regions is consistent with these proposed dissociations. We predicted greater connectivity of anterior hippocampus with putative generalization regions and posterior hippocampus with putative memory specificity regions. Furthermore, we tested whether differences in connectivity are stable under varying levels of task engagement. Participants learned to categorize a set of stimuli outside the scanner, followed by an fMRI session that included a rest scan, passive viewing runs, and category generalization task runs. Analyses revealed stronger connectivity of ventromedial pFC to anterior hippocampus and of angular gyrus and inferior frontal gyrus to posterior hippocampus. These differences remained relatively stable across the three phases (rest, passive viewing, category generalization). Whole-brain analyses further revealed widespread cortical connectivity with both anterior and posterior hippocampus, with relatively little overlap. These results contribute to our understanding of functional organization along the long axis of the hippocampus and suggest that distinct hippocampal–cortical connections are one mechanism by which the hippocampus represents both individual experiences and generalized knowledge.

Objective To evaluate whether cognitive reserve (CR) moderates the relationship between neuropathology and cognitive outcomes after traumatic brain injury (TBI). Setting Outpatient research organization. Participants Patients with complicated mild (n = 8), moderate (n = 9), and severe (n = 44) TBI. Design Prospective, cross-sectional study. Main measures Cognitive reserve was estimated using a test of word reading (Wechsler Test of Adult Reading). Diffusion tensor imaging (functional anisotropy) was used to quantify neuropathology. Neuropsychological test scores were submitted to principal components analyses to create cognitive composites for memory, attention, executive function, and processing speed domains. Results At lower levels of neuropathology, people with higher CR exhibited better memory than those with lower CR. This benefit diminished as neuropathology increased and disappeared at the highest levels of neuropathology. Cognitive reserve ceased exerting a protective effect at premorbid intelligence levels below average. Conclusion Cognitive reserve may differentially protect some cognitive domains against neuropathology relative to others. A clinical cutoff below which CR is no longer protective, together with a possible neuropathology ceiling effect, may be instructive for prognostication and clinical decision-making in cognitive rehabilitation.

Background 13‐Deoxy, 5‐iminodoxorubicin (GPX‐150) is a doxorubicin (DOX) analog synthesized to reduce the formation of reactive oxygen species and the cardiotoxic metabolite, doxorubiciniol, the two pathways that are linked to the irreversible, cumulative dose‐dependent cardiotoxicity of DOX. In a preclinical chronic models and a phase I clinical study of GPX‐150, no irreversible, cumulative dose‐dependent cardiotoxicity was demonstrated. Recent studies suggest that DOX cardiotoxicity may be mediated, at least in part, by the poisoning of topoisomerase IIβ. Patients and Methods An open‐label, single‐arm phase II clinical study in metastatic and unresectable soft tissue sarcoma (STS) patients was initiated to further evaluate the efficacy and safety of GPX‐150, including cardiac function, specifically left ventricular ejection fraction (LVEF). Results GPX‐150 was administered at 265 mg/m2 every 3 weeks for up to 16 doses with prophylactic G‐CSF until progression, death, or patient withdrawal from the study. GPX‐150 exhibited efficacy assessed as progression‐free survival (PFS) rates of 38% and 12% at 6 and 12 months and an overall survival rate of 74% and 45% at 6 and 12 months. GPX‐150–treated patients did not develop any evidence of irreversible, cumulative dose‐dependent chronic cardiotoxicity. Toxicities included grade 3 anemia, neutropenia, and one grade 4 leukopenia. Correlative analysis demonstrated that GPX‐150 was more selective than DOX for the inhibition of topoisomerase IIα over IIβ in vitro. Conclusion These results suggest future studies are warranted to further evaluate the clinical efficacy of GPX‐150 in STS, perhaps at doses higher than 265 mg/m2.

External motivation, such as a promise of future monetary reward for remembering an event, can affect which events are remembered. Reward-based memory modulation is thought to result from encoding and post-encoding interactions between dopaminergic midbrain, signaling reward, and hippocampus and parahippocampal cortex, supporting episodic memory. We asked whether hippocampal and parahippocampal interactions with other reward-related regions are related to reward modulation of memory and whether such relationships are stable over time. Individuals' memory sensitivity to reward was measured using a monetary incentive encoding task in which a cue indicated potential monetary reward (penny, dime, or dollar) for remembering an upcoming object pair. Functional connectivity between memory and reward regions was measured before, during, and following the task. Reward-related regions of interest were generated using a meta-analysis of existing studies on reward and included ventral striatum, medial and orbital prefrontal cortices and anterior cingulate cortex, in addition to midbrain. The results showed that connectivity between memory and reward regions tracked individual differences in reward modulation of memory, irrespective of when connectivity was measured. Connectivity patterns of anterior cingulate, orbitofrontal cortex, and ventral striatum covaried together and tracked behavior most strongly. These findings implicate a broader set of reward regions in reward modulation of memory than considered previously and provide new evidence that stable connectivity patterns between memory and reward centers relate to individual differences in how reward impacts memory.

Item does not contain fulltext BACKGROUND: Sepsis is a leading cause of morbidity and mortality after surgery. Most studies regarding sepsis do not differentiate between patients who have had recent surgery and those without. Few data exist regarding the risk factors for poor outcomes in pediatric postsurgical sepsis. Our hypothesis is pediatric postsurgical, and medical patients with severe sepsis have unique risk factors for mortality. METHODS: Data were extracted from a secondary analysis of an international point prevalence study of pediatric severe sepsis. Sites included 128 pediatric intensive care units from 26 countries. Pediatric patients with severe sepsis were categorized into those who had recent surgery (postsurgical sepsis) versus those that did not (medical sepsis) before sepsis onset. Multivariable logistic regression models were used to determine risk factors for mortality. RESULTS: A total of 556 patients were included: 138 with postsurgical and 418 with medical sepsis. In postsurgical sepsis, older age, admission from the hospital ward, multiple organ dysfunction syndrome at sepsis recognition, and cardiovascular and respiratory comorbidities were independent risk factors for death. In medical sepsis, resource-limited region, hospital-acquired infection, multiple organ dysfunction syndrome at sepsis recognition, higher Pediatric Index of Mortality-3 score, and malignancy were independent risk factors for death. CONCLUSIONS: Pediatric patients with postsurgical sepsis had different risk factors for mortality compared with medical sepsis. This included a higher mortality risk in postsurgical patients presenting to the intensive care unit from the hospital ward. These data suggest an opportunity to develop and test early warning systems specific to pediatric sepsis in the postsurgical population.

ObjectiveTo report safety, pharmacokinetics, exon 53 skipping, and dystrophin expression in golodirsen-treated patients with Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping.MethodsPart 1 was a randomized, double-blind, placebo-controlled, 12-week dose titration of once-weekly golodirsen; part 2 was an open-label evaluation. Safety and pharmacokinetics were primary and secondary objectives of part 1. Primary biological outcome measures of part 2 were blinded exon skipping and dystrophin protein production on muscle biopsies (baseline, week 48) evaluated, respectively, using reverse transcription PCR and Western blot and immunohistochemistry.ResultsTwelve patients were randomized to receive golodirsen (n = 8) or placebo (n = 4) in part 1. All from part 1 plus 13 additional patients received 30 mg/kg golodirsen in part 2. Safety findings were consistent with those previously observed in pediatric patients with DMD. Most of the study drug was excreted within 4 hours following administration. A significant increase in exon 53 skipping was associated with ∼16-fold increase over baseline in dystrophin protein expression at week 48, with a mean percent normal dystrophin protein standard of 1.019% (range, 0.09%–4.30%). Sarcolemmal localization of dystrophin was demonstrated by significantly increased dystrophin-positive fibers (week 48,p< 0.001) and a positive correlation (Spearmanr= 0.663;p< 0.001) with dystrophin protein change from baseline, measured by Western blot and immunohistochemistry.ConclusionGolodirsen was well-tolerated; muscle biopsies from golodirsen-treated patients showed increased exon 53 skipping, dystrophin production, and correct dystrophin sarcolemmal localization.Clinicaltrials.gov identifierNCT02310906.Classification of evidenceThis study provides Class I evidence that golodirsen is safe and Class IV evidence that it induces exon skipping and novel dystrophin as confirmed by 3 different assays.

PURPOSE: To evaluate which parameters may affect endothelial cell loss after Descemet membrane endothelial keratoplasty (DMEK) by comparing eyes in the low vs high quartile of endothelial cell loss over a follow-up period of 4 years.DESIGN: Retrospective cohort study.METHODS: Donor endothelial cell density (ECD) decline was evaluated for 351 eyes of 275 patients up to 4 years after DMEK for Fuchs endothelial corneal dystrophy (FECD). Eyes with a postoperative endothelial cell loss in the lower quartile at all available follow-up moments were assigned to Group 1 (n = 51) and those in the upper quartile to Group 2 (n = 42). Multinomial regression was used to assess which covariates were related to greater ECD decline.RESULTS: Mean endothelial cell loss as compared to preoperative donor ECD for the entire study group was 33 (+/- 16)%, 36 (+/- 17)%, and 52 (+/- 18)% at 1, 6, and 48 months postoperatively. Endothelial cell loss of Group 1 was 12 (+/- 7)%, 13 (6)%, and 26 (+/- 8)% at, respectively, 1, 6, and 48 months postoperatively, and 59 (+/- 10)%, 64 (+/- 9)%, and 75 (+/- 5)% in Group 2. Partial graft detachment, donor death cause cardiovascular/stroke (vs cancer), postoperative complications other than graft detachment, and severity of preoperative FECD (all P

Motivation enhances memory by increasing hippocampal engagement during encoding. However, whether such increased hippocampal activation reflects encoding of the value of highly rewarding events per se is less understood. Here, using a monetary incentive encoding task with a novel manipulation, we tested in humans whether the hippocampus represents abstract reward value, independent of perceptual content. During functional MRI scanning, men and women studied object pairs, each preceded by a monetary reward cue indicating the amount of money they would receive if they successfully remembered the object pair at test. Reward cues varied on both the level of reward (penny, dime, and dollar) and visual form (picture or word) across trials to dissociate hippocampal responses to reward value from those reflecting the perceptual properties of the cues. Behaviorally, participants remembered pairs associated with the high reward (dollar) more often than pairs associated with lower rewards. Neural pattern-similarity analysis revealed that hippocampal and parahippocampal cortex activation patterns discriminated between cues of different value regardless of their visual form, and that hippocampal discrimination of value was most pronounced in participants who showed the greatest behavioral sensitivity to reward. Strikingly, hippocampal patterns were most distinct for reward cues that differed in value but had similar visual appearance, consistent with theoretical proposals of hippocampal-pattern differentiation of competing representations. Our data illustrate how contextual representations within the hippocampus go beyond space and time to include information about the motivational salience of events, with hippocampal reward coding tracking the motivational impact on later memory.SIGNIFICANCE STATEMENTMotivation, such as the promise of future rewards, enhances hippocampal engagement during encoding and promotes successful retention of events associated with valuable rewards. However, whether the hippocampus explicitly encodes reward value, dissociable from sensory information, is unclear. Here, we show that the hippocampus forms abstract representation of valuable rewards, encoding conceptual rather than perceptual information about the motivational context of individual events. Reward representation within the hippocampus is associated with preferential retention of high-value events in memory. Furthermore, we show that hippocampal-pattern differentiation serves to emphasize differences between visually similar events with distinct motivational salience. Collectively, these findings indicate that hippocampal contextual representations enable individuals to distinguish the motivational value of events, leading to prioritized encoding of significant memories.

The reading frame rule suggests that Duchenne muscular dystrophy (DMD) results from DMD mutations causing an out-of-frame transcript, whereas the milder Becker muscular dystrophy results from mutations causing an in-frame transcript. However, predicted nonsense mutations may instead result in altered splicing and an in-frame transcript. Here we report a 10-year-old boy with a predicted nonsense mutation in exon 42 who had a 6-minute walk time of 157% of that of age matched DMD controls, characterized as intermediate muscular dystrophy. RNA sequencing analysis from a muscle biopsy revealed only 6.0–9.8% of DMD transcripts were in-frame, excluding exon 42, and immunoblot demonstrated only 3.2% dystrophin protein expression. Another potential genetic modifier noted was homozygosity for the protective IAAM LTBP4 haplotype. This case suggests that very low levels of DMD exon skipping and dystrophin protein expression may result in amelioration of skeletal muscle weakness, a finding relevant to current dystrophin-restoring therapies.

Natural olfactory stimuli are volatile-chemical mixtures in which relative perceptual saliencies determine which odor-components are identified. Odor identification also depends on rapid selective adaptation, as shown for 4 odor stimuli in an earlier experimental simulation of natural conditions. Adapt-test pairs of mixtures of water-soluble, distinct odor stimuli with chemical features in common were studied. Identification decreased for adapted components but increased for unadapted mixture-suppressed components, showing compound identities were retained, not degraded to individual molecular features. Four additional odor stimuli, 1 with 2 perceptible odor notes, and an added “water-adapted” control tested whether this finding would generalize to other 4-compound sets. Selective adaptation of mixtures of the compounds (odors): 3 mM benzaldehyde (cherry), 5 mM maltol (caramel), 1 mM guaiacol (smoke), and 4 mM methyl anthranilate (grape-smoke) again reciprocally unmasked odors of mixture-suppressed components in 2-, 3-, and 4-component mixtures with 2 exceptions. The cherry note of “benzaldehyde” (itself) and the shared note of “methyl anthranilate and guaiacol” (together) were more readily identified. The pervasive mixture-component dominance and dynamic perceptual salience may be mediated through peripheral adaptation and central mutual inhibition of neural responses. Originating in individual olfactory receptor variants, it limits odor identification and provides analytic properties for momentary recognition of a few remaining mixture-components.

To evaluate the clinical outcome of 500 consecutive cases up to 2 years after Descemet membrane endothelial keratoplasty (DMEK) and to assess which parameters may have influenced the clinical outcome.From a group of 500 eyes (393 patients), which underwent DMEK for Fuchs endothelial corneal dystrophy (FECD), bullous keratopathy, failed corneal transplants and other indications, clinical outcomes [best-corrected visual acuity (BCVA), central endothelial cell density (ECD), and central corneal thickness] were evaluated before, and at 6, 12, and 24 months after DMEK and postoperative complications were documented.At 12 months postoperatively, 81% of eyes reached a BCVA of ≥20/25 (≥0.8), 49% ≥20/20 (≥1.0), and 15% ≥20/18 (≥1.2) (n = 396) and remained stable up to 24 months (P = 0.828). Compared with preoperative ECD, mean postoperative ECD decreased by 37 (±18)%, 40 (±18)%, and 45 (±18)% at 6, 12, and 24 months, respectively (P0.05 for all time points). Surgery indication and graft attachment status were related to postoperative BCVA and ECD results. Eyes with FECD and attached grafts showed better BCVA outcomes and higher ECD (P0.05). Central corneal thickness decreased by 20 (±11)% to 525 (±46) μm from preoperative to 6 months postoperatively and remained stable thereafter (P0.05). Within the study period, retransplantation was required in 32 eyes (6.4%). Principal longer-term complications were secondary graft failure (1.4%) and allograft rejection (1.4%).Clinical outcomes remain excellent up to 2 years after DMEK, in particular for eyes operated on for FECD and with completely attached grafts.

Background Implementation researchers have typically studied organizational culture and climate by testing whether individual dimensions are linked to the implementation of evidence-based practices (EBPs) rather than examining how the overarching social context influences implementation. This approach may limit implementation theory and strategy development to the extent that individual dimensions of culture and climate interact, mutually reinforce or counteract one another, or exhibit non-linear relationships. This study tests whether empirically identifiable culture and climate profiles emerge in a sample of organizations and examines how these profiles relate to EBP fidelity and work attitudes that support EBP sustainment, focusing on three EBPs for youth with autism delivered in schools as an example. Methods The study included 65 elementary schools in the U.S. that implemented three EBPs—discrete trial training, pivotal response training, and visual schedules—for youth with autism. Organizational culture and climate and work attitudes were assessed using the Organizational Social Context measure at the beginning of the school year. Observations of EBP fidelity occurred mid school-year. We used bias-adjusted stepwise latent profile modeling to (1) identify subpopulations of schools that share similar culture and climate profiles, and (2) test for mean differences across profiles in observed EBP fidelity and teacher and staff work attitudes. Results Controlling for region, four profiles best characterized the organizational cultures and climates of schools. Teachers and staff in schools with a comprehensive profile (high proficiency culture, positive climate) exhibited higher fidelity to two of three EBPs (d’s = .95 to 1.64) and reported superior work attitudes (d’s = .71 to 1.93) than teachers and staff in all other schools. Teachers and staff in supportive schools (low rigidity culture, positive climate) had better work attitudes, but not better fidelity, than those in schools with indifferent (low culture/climate, elevated stress) and constrained (high rigidity and resistance, high stress) profiles. Conclusions Organizational culture and climate profiles are a strong predictor of EBP fidelity and work attitudes that support EBP sustainment, highlighting the importance of an organization’s overarching social context when developing implementation theory and strategies. Strategies that foster a comprehensive profile may improve EBP implementation. Electronic supplementary material The online version of this article (10.1186/s13012-019-0863-9) contains supplementary material, which is available to authorized users.

Objective The goal of this study was to explore the association of timing of and frequency of meals with markers of cardiometabolic risk in patients with bipolar disorder in out-patient maintenance treatment. Methods We used Pittsburgh Sleep Diary and actigraphy measures for individuals with bipolar I disorder. Linear and logistic regression analyses were used to determine whether dinnertime, instability of dinnertime, and/or interval between meals were associated with metabolic syndrome and its components. Results Later dinnertime was associated with greater waist circumference (β = 0.25, P = 0.02) after adjusting for age, sex, dinner-to-bed interval, and sleep duration. Longer breakfast-to-lunch intervals were also associated with greater waist circumferences (β =−.35, P = .002) after adjusting for age, sex, and sleep duration. Neither instability of dinnertime nor number of meals per day was associated with the metabolic syndrome or its components. Conclusion Weight gain is often perceived as inevitable side-effect of medications. While patients often need to be on medication to function, a more careful lifestyle assessment with attention to social rhythms and timing of activities may be critical not only for mood stability, but also to reduce cardiovascular risk.

Objective This study measured a variety of within-exposure fear changes and tested the relationship of each with treatment outcomes in exposure therapy. Method We coded 459 videotaped exposure tasks from 111 participants in 3 clinical trials for pediatric obsessive-compulsive disorder (OCD; POTS trials). Within exposures, fear level was observed continuously and alongside exposure process. Fear change metrics of interest were selected for relevance to mechanistic theory. Fear decreases were classified by function; nonhabituation decreases were associated with observed nonlearning processes (e.g., avoidance), whereas habituation decreases appeared to result from an internal and indirect process. Outcomes were posttreatment change in symptom severity, global improvement, and treatment response. Results Greater cumulative habituation across treatment was associated with larger reductions in symptom severity, greater global improvement, and increased odds of treatment response. Fear activation, fear variability, and nonhabituation fear decreases did not predict any outcomes. Exploratory analyses examined fear changes during habituation and nonhabituation exposures; higher peak fear during nonhabituation exposures was associated with attenuated global improvement. Conclusions Habituation is conceptually consistent with multiple mechanistic theories and should continue to be investigated as a practical marker of initial extinction learning and possible moderator of the relationship between fear activation and outcome. Results support the importance of functional and frequent fear measurement during exposures, and discussion considers implications of these findings for future studies aiming to understand learning during exposure and improve exposure delivery. (PsycINFO Database Record

Previous work investigating tricyclic pyrrolopyrazines as kinase cores led to the discovery that 1-cyclohexyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (12) had Jak inhibitory activity. Herein we describe our initial efforts to develop orally bioavailable analogs of 12 with improved selectivity of Jak1 over Jak2.

This study replicates and extends prior research on the relationship of childhood complex trauma (CCT) and complex posttraumatic stress disorder (cPTSD) in adulthood, examining the role of psychoform and somatoform dissociation as a potential mediator. CCT, dissociation, and cPTSD were assessed in a large sample of adult psychiatric inpatients. Almost two thirds of participants reported having experienced CCT. Path analyses with bootstrap confidence intervals demonstrated a relationship between CCT, psychoform (but not somatoform) dissociation, and cPTSD. In addition, psychoform dissociation partially mediated the relationship between CCT and adult cPTSD symptoms. Dissociation (pathological or nonpathological psychoform and somatoform symptoms) warrants further clinical and scientific study as a potential link between CCT and the presence of adult cPTSD symptoms and/or the dissociative subtype of PTSD.

The present study developed parallel clinician- and parent-rated measures of family accommodation (Pediatric Accommodation Scale, PAS; Pediatric Accommodation Scale-Parent Report; PAS-PR) for youth with a primary anxiety disorder. Both measures assess frequency and impact of family accommodation on youth and families. Studying youth ages 5-17 (N=105 caregiver-youth dyads), results provide evidence for the psychometric properties of the PAS, including internal consistency, inter-rater reliability, and convergent and discriminant validity. The PAS-PR exhibited good internal consistency and convergent validity with the PAS. Nearly all parents (>95%) endorsed some accommodation and accommodation frequency was associated with parent-rated impairment (home and school), and with youth-rated impairment (school only). Greater impact of accommodation on parents was associated with parent self-reported depressive symptoms. Findings support the common occurrence of family accommodation in youth with anxiety disorders, as well as for the use of the PAS and PAS-PR to measure family accommodation in this population.

To report the 6-month clinical outcomes of a large cohort of Descemet membrane endothelial keratoplasty (DMEK) eyes operated by 55 starting or experienced surgeons.This is a retrospective, multicenter, interventional, cohort study with a total of 2485 eyes. Best-corrected visual acuity (BCVA), endothelial cell density (ECD) decrease, and intra- and post-operative complications were evaluated. Three groups based on case order were compared: group I (cases 1-24), group II (cases 25-99), and group III (cases ≥100). Forty-nine percent of the surgeons were in their learning curve (25 cases), representing 10.4% of the surgeries.Six months after DMEK, BCVA improved in 90.5% of eyes, remained unchanged in 4.6%, and deteriorated in 4.9% (n = 1936); 75.4% of eyes reached a BCVA of ≥20/40 (≥0.5), 45.4% ≥20/25 (≥0.8), and 25.8% ≥20/20 (≥1.0) (n = 1959) and ECD decreased by 40% (±19) (n = 1272, P0.05). BCVA and ECD outcomes did not differ between groups I and III (P0.05). Intraoperative complications were reported for 9.4% of eyes, whereas graft detachment was the main postoperative complication (27.4%), with lower intra- and post-operative complication rates in group III than group I (P0.05). Rebubbling was performed in 20.1% of eyes; 13.8% required secondary keratoplasty within 6 months.DMEK is applicable for surgeons in various settings with good clinical outcomes. After an arbitrary learning curve (25 cases), virtually all transplant-related complications declined with experience. Notably, surgeons with a higher annual caseload may pass faster through their learning curve than surgeons performing their first surgeries over an extended period.

Purpose To assess the clinical outcome after successful rebubbling procedures for visually significant graft detachment after Descemet membrane endothelial keratoplasty (DMEK). Methods From a total of 760 consecutive DMEK surgeries, 41 eyes required rebubbling. Of those, 33 eyes of 31 patients were successful and were included in our retrospective outcome analysis study. Main outcome measures were compared with those of matched controls with uneventful primary DMEK (attached DMEK grafts without rebubbling). Rebubbling was performed on average 25 (±20) days (range 7-91 days) after DMEK. All eyes were evaluated for best-corrected visual acuity, endothelial cell density (ECD), pachymetry, and complications up to 6 months after rebubbling. Results At 6 months after DMEK, best-corrected visual acuity in rebubbled eyes did not differ from that in control eyes (P = 0.514). The mean ECD decrease was higher in rebubbled than in control eyes (54% vs. 35%, respectively, P = 0.001). Pachymetry did not differ between both groups (P = 0.153). After rebubbling, one buphthalmic eye showed temporary intraocular pressure elevation and 5 eyes had minor graft edge detachment that did not require further treatment. Conclusions Rebubbling for DMEK graft detachment may result in similar visual outcomes as in uncomplicated DMEK, when performed within the first 6 to 8 postoperative weeks. However, rebubbled eyes may have lower ECD, which may be attributed to additional air bubble trauma and/or selection bias through more extensive manipulation during initial DMEK or higher risk of graft detachment in more complicated eyes.

Although research findings in taste and olfaction contribute to key questions in basic science, it is results directly relevant to human health that more frequently arouse heightened interest. One of the most exciting observations in recent years was the demonstration that intraperitoneal (IP) injection of the anorexigenic hormone leptin, a key regulator of body weight, reduced both peripheral chorda tympani (CT) and glossopharyngeal (GL) responses elicited by oral stimulation with sweeteners (Kawai et al. 2000). This landmark study also revealed that the leptin receptor (LepRbs) was expressed in a subset of taste bud cells and that bath application of leptin hyperpolarized some cells in the bud. Many questions remained but the effects themselves were robust and seemingly straightforward. These findings suggested that part of leptin’s action in regulating food intake and body weight is through direct effects on the initial stages of processing in the taste system. The implied interpretation was that leptin, which is produced by adipocytes, and which is therefore more plentiful in well-nourished versus poorly nourished animals and in the sated versus the deprived state, decreases the magnitude of the afferent “sweet” signal, which leads to suppression of intake of these caloric substances (Figure 1). Figure 1. Left: In several brain regions, leptin binding to the long-form of the LepRbs has well-documented anorexigenic effects. Right: The LepRbs is also expressed in taste buds, primarily in Type II cells. Leptin effects on taste bud responses to sweet stimuli ... In this issue of Chemical Senses, Steven Roper’s group shows that leptin decreases sweet stimulus-evoked release of ATP from taste bud cells but increases 5-HT release. Since ATP is known to have excitatory effects on primary afferent taste fibers, and 5-HT is thought to inhibit ATP release, these findings are in line with the observations of Ninomiya’s group. The observations make a coherent, satisfying story. However, a caveat is in order given the recent findings of Scott Herness’ group that 5-HT has facilitatory effects on CT responses (Jaber et al. 2014). Moreover, a few years ago, the laboratory of Robert Contreras (Lu et al. 2012) demonstrated that leptin slightly increased, rather than decreased, CT responses to sweeteners. To further complicate the tale, in this issue of Chemical Senses, John Glendinning and colleagues report that leptin has no effect on the magnitude of CT responses to sweet stimuli. What could be the basis for these disparate observations? And, how does the variability impact interpretation of taste-bud leptin’s functional significance? One possibility, originally discussed by Contreras and colleagues, is stimulus temperature. Indeed, experiments showing suppression of peripheral sweet-evoked responses used room temperature stimuli whereas those showing slight or no effect used stimuli near normal body temperature. How stimulus temperature could contribute to these effects is not entirely obvious. Larger responses based on temperature-sensitive elements such as TRPM5 in the taste transduction cascade could conceivably obscure suppression (Talavera et al. 2005) but this seems unlikely given the wide range of stimulus concentrations and response magnitudes already scrutinized. To be definitive, the stimulus temperature hypothesis needs direct testing; if proven that increased temperature obscures leptin’s effects, its ultimate functional impact would be compromised. Moreover findings of Glendinning’s group, also in the current issue, appear to contradict those of Ninomiya’s group regarding behavioral effects of leptin. Based on licking a wide-range of sweetener + quinine (3mM) mixtures for 10-s, Shigemura et al. (2004) concluded that that behavioral responsiveness to sweet-tasting stimuli was reduced by increases in circulating leptin. However, based on similar 5-s tests of pure sucrose or saccharin, Glendinning and colleagues fail to show an effect of IP leptin. Given that IP injections of leptin have access to central as well as peripheral LepRbs and perception of the intensity of sweetness in a sweet-bitter mixture also involves bitter-suppressive effects, potential explanations for differences in experimental outcomes are many. Regardless, the original simple interpretation that changes in leptin levels decrease peripheral sweet signaling to a degree demonstrable behaviorally is conditional. In any case, it is clear that behaviorally significant peripheral effects of leptin are subject to additional, probably unidentified influences. Indeed, Niki et al. (2013) recently reported that leptin effects on peripheral taste responses were obscured when baseline circulating levels of leptin exceeded 10ng/mL. This is not the basis for the lack of effect seen by Glendinning and colleagues, who observed much lower baseline levels of leptin. Their Figure 2 also indicates that ob/ob mice, which do not produce leptin, do not show larger CT control sugar responses. Whereas, Ninomiya’s group previously showed that peripheral responses to sweet stimuli were larger in obese db/db mice (Ninomiya et al. 1998; Sako et al. 1996), which lack a functional LepRbs. The situation with obesity is complicated because obese individuals may have higher levels of leptin but yet be leptin-resistant. This is an important reminder of the many sources of regulation with potential to affect peripheral taste responses and the complex regulatory pathways that underlie homeostasis. Points of agreement among reports on the peripheral effects of leptin in the gustatory system are worth noting. A consistent finding is that the LepRbs is expressed on taste bud cells, as shown by immunohistochemistry (Cai et al. 2014; Kawai et al. 2000), polymerase chain reaction (Cai et al. 2014; Kawai et al. 2000; Shigemura et al. 2003), in situ hybridization (Shigemura et al. 2003) or by the transgenic expression of fluorescent markers in the Glendinning group’s current study. Interestingly, Glendinning and colleagues’ findings reveal that expression of the long form LebRbs is restricted largely to Type II cells, something that had been suspected previously but not conclusively demonstrated. Thus, the interesting observation by the Roper group that sucrose-evoked 5-HT release by Type III cells is augmented by leptin may not directly involve leptin binding to a receptor on Type III cells. Glendinning and colleagues also show that, in contrast to most LepRbs in the brain, leptin does not induce phosphorylation of the transcription factor, STAT3, suggesting that one of the several alternate signaling pathways (Allison and Myers 2014) is probably engaged by leptin in taste bud cells (Figure 1). Agreement that demonstrated peripheral gustatory effects of leptin are selective for sweet-tasting stimuli is also significant. No influences on salty, sour, and bitter responses were detected. Umami stimuli have not been routinely tested, although alterations in monosodium glutamate responses were not seen in one study demonstrating sucrose-response increases. However, specific susceptibilities of sweet-elicited CNS responses to manipulations related to body weight regulation were seen previously. Changes in blood glucose and insulin suppressed responses to sugars in the first-order taste relay, the nucleus of the solitary tract (Giza and Scott 1983; Giza and Scott 1987; Giza et al. 1992), as did intraduodenal lipid infusions in the parabrachial nucleus (Hajnal et al. 1999). A high-fat diet that produced obesity selectively increased sweet-elicited responses in the parabrachial nucleus in OLETF rats with spontaneous knockout of CCK-1 receptors (Hajnal et al. 2010). The new findings in this issue of Chemical Senses leave the field with an important challenge. Collectively, the existing data make a compelling case that leptin is a significant regulator in the peripheral taste system. However, its function appears to be under more complex control than initially envisioned by Ninomiya and his colleagues. Leptin’s biological function in the taste bud may not simply parallel its central role in suppressing food intake, but include other modulatory or even developmental or cell biological roles. Indeed, a large number of peptides, transmitters and their receptors have been identified in the taste bud (reviewed in Dotson et al. 2013; Herness and Zhao 2009; Roper 2013) but understanding the functional logic of taste bud circuitry, including the role of leptin, remains incomplete.

Background Bipolar disorder II (BPII) and unipolar depression (UD) are both characterized by episodes of major depression (MDE), however DSM-IV criteria for MDE are identical, regardless of diagnosis. As a result, misdiagnosis of BP II and UD is common, leading to inappropriate treatment. Because women are twice as likely as men to experience MDE, differentiating UD from BP II in the context of depression is especially important for women. We examined symptoms and clinical features of MDE in women with UD and BPII to compare presentations of the two disorders in women. Methods We compared characteristics of depressed women meeting DSM-IV criteria for BPII (n=48) or UD (n=48), matched on age. Results Feelings of worthlessness occurred in 98% of participants with UD versus 85% with BPII (p=0.03). Participants with UD experienced either insomnia or hypersomnia, but participants with BPII were more likely to experience both simultaneously (p=0.04). Those with UD were significantly less likely to have >5 prior mood episodes compared to those with BP II (12% versus 61%; p Limitations Small sample size and exclusion criteria (i.e., comorbid substance abuse) may limit generalizability of findings. Conclusions Among a sample of women, number of prior episodes, feelings of worthlessness, age of onset, and sleep patterns distinguished between UD and BP II depressive episodes. A better understanding of differential presentation of BP II versus UD depression in women may help guide clinicians to more accurate diagnoses and, ultimately, better treatment.

Background and Purpose— Alterations of cerebral glucose metabolism are well anticipated during cerebral ischemia. However, detailed spatiotemporal characteristics of disturbed cerebral glucose metabolism during acute ischemia remain largely elusive. This study aims to delineate spatiotemporal distributions of [ 18 ]F-2-fluoro-2-deoxy- d -glucose (FDG) uptake using positron emission tomography imaging, particularly at the peri-ischemic zone, and its correlation with tissue outcome. Methods— The intraluminal suture middle cerebral artery occlusion model was used to induce focal cerebral ischemia in rats (n=48). All animals underwent sequential MRI and FDG positron emission tomography imaging at different times (30–150 minutes) after middle cerebral artery occlusion. MR and positron emission tomography images were coregistered. FDG uptake in the peri-ischemic zone was assessed in relation to middle cerebral artery occlusion duration, cerebral blood flow, apparent diffusion coefficient, and 24-hour T2 lesions. Results— Elevated FDG uptake was consistently observed at the peri-ischemic zone surrounding the presumed ischemic core with low FDG uptake. Both the spatial volume and the uptake level of the hyper-uptake region were inversely correlated with the duration of middle cerebral artery occlusion. The hyper-uptake regions exhibited a mild reduction of cerebral blood flow (28.2±3.2%) and apparent diffusion coefficient (9.1±1.4%) when compared with that in the contralateral hemisphere. Colocalization analysis revealed that, with reperfusion, an average of 12.1±1.7% of the hyper-uptake volume was recruited into final infarction. Conclusions— Elevated FDG uptake at the peri-ischemic zone is consistently observed during acute cerebral ischemia. The region with elevated FDG uptake likely reflects viable tissues that can be salvaged with reperfusion. Therefore, acute FDG positron emission tomography imaging might hold promise in the management of patients with acute stroke.

To evaluate the incidence and causes of anterior corneal surface irregularities after successful Descemet membrane endothelial keratoplasty (DMEK) and the efficacy of contact lens fitting in these cases.Tertiary referral center.Retrospective study of prospectively collected data.Eyes with a subnormal visual outcome or monocular diplopia after successful DMEK were fitted with a contact lens. These cases were evaluated with Pentacam rotating Scheimpflug camera imaging preoperatively and 6 months postoperatively, and outcomes were compared with those in a randomly selected DMEK control group.In a series of 262 surgeries, 23 eyes (21 patients) were fitted with contact lenses; the control group comprised 23 eyes. Indications for contact lens fitting included (1) obvious corneal surface irregularities due to preexisting corneal scarring, (2) surface irregularities associated with longstanding preoperative stromal edema, and (3) undetectable optical imperfections. The postoperative corrected distance visual acuity (CDVA) with spectacles improved after contact lens correction (P.001). Preoperative and postoperative irregularity indices were significantly higher in the contact lens group than in the DMEK control group (P.05). Positive correlations were found between the duration of preoperative stromal edema and postoperative Scheimpflug camera indices (P.02).After successful DMEK, 23 of 262 eyes (9%) showed subnormal spectacle CDVA and/or monocular diplopia due to corneal scarring, surface irregularities, or undetectable optical imperfections that could be managed by contact lens fitting. Prolonged preoperative corneal edema for more than 12 months may be a risk factor for diffuse irregular astigmatism after DMEK.Dr. Melles is a consultant to DORC International BV/Dutch Ophthalmic USA. No author has a financial or proprietary interest in any material or method mentioned.

To monitor refractive changes after Descemet membrane endothelial keratoplasty (DMEK) and to determine what may influence these changes and the time point of stabilization.From 67 pseudophakic DMEK eyes operated on for Fuchs endothelial dystrophy at a tertiary referral center, biomicroscopy, visual acuity, subjective refraction, and Scheimpflug-based corneal tomography data were obtained before and up to 2 years postoperatively. Visual acuity and changes in spherical equivalent (SE), mean anterior and posterior simulated keratometry (Km), and central pachymetry were analyzed.At 3 months postoperatively, both hyperopic (28/67 eyes) and myopic (21/67 eyes) shifts were observed; 18/67 eyes showed no SE change. The mean change in SE at 3 months was +0.33 diopters (D) (95% confidence interval = [0.11, 0.54], P = 0.028), which stabilized thereafter (P0.466). Initial flattening of mean anterior Km by 0.66D (95% confidence interval = [-0.81, -0.51], P0.001) at 3 months was followed by a slow steepening, which became significant between 1 and 2 years postoperatively (P0.001). Posterior Km stabilized after 3 months (P0.252). Preoperative to 3 months postoperative absolute changes in anterior Km were positively related to preoperative backscattered light from the central anterior cornea (P = 0.035), and the presence of partial graft detachment postoperatively (P = 0.013).After DMEK, SE and posterior corneal curvature were on average stable at 3 months after surgery, whereas the mean anterior corneal curvature showed an ongoing gradual change. Changes in anterior corneal curvature may be related to preoperative anterior corneal densitometry or postoperative partial graft detachment.

Studies of nicotine consumption in rodents often intend to investigate nicotine's post-absorptive effects, yet little is known about the pre-absorptive sensory experience of nicotine drinking, including gustatory, trigeminal, and olfactory influences. We conditioned taste aversion (CTA) to nicotine in males of 3 inbred mouse strains: C57BL/6J, DBA/2J, and 129X1/SvJ by repeatedly pairing 150 μg/ml nicotine drinking with lithium chloride injections. Generalization to a variety of bitter, sour, sweet, salty, and irritant solutions and to nicotine odor was then examined. Nicotine CTA generalized to the bitter stimulus quinine hydrochloride and the chemosensory irritant spilanthol in all strains. It also showed strain specificity, generalizing to hydrogen peroxide (an activator of TRPA1) in C57BL/6J mice and to the olfactory cue of nicotine in DBA/2J mice. These behavioral assays demonstrate that the sensory properties of nicotine are complex and include multiple gustatory, irritant, and olfactory components. How these qualities combine at the level of perception remains to be assessed, but sensory factors clearly exert an important influence on nicotine ingestion and their contribution to net intake of nicotine should not be neglected in animal or human studies.

Effects of cathodal current, which draws cations away from the tongue and drives anions toward the tongue, depend on the ionic content of electrolytes through which the current is passed. To address the role of cations and anions in human salt tastes, cathodal currents of -40 microA to -80 microA were applied to human subjects' tongues through supra-threshold salt solutions. The salts were sodium chloride, sodium bromide, potassium chloride, ammonium chloride, calcium chloride, sodium nitrate, sodium sulfate, sodium saccharin, sodium acetate and sodium benzoate, which taken together encompass salty, bitter, sour and sweet taste qualities. The taste of NaCl, the salty and bitter tastes of the other chloride salts and the taste of NaNO(3) was inhibited, suggesting the current displaced stimulatory cations from salty and bitter receptors. However, bitter tastes of non-halide sodium salts were not inhibited, likely because other bitter receptors respond to anions. A discharge current at cathode-off ubiquitously evoked a metallic taste reminiscent of anodal taste used in clinical electrogustometry. Analogous effects on ambient NaCl responses were recorded from the hamster chorda tympani nerve. Increases in tastes of the saccharin and benzoate anions were not evoked during current flow, suggesting that cathodal current does not carry stimulatory anions to sweet receptors. Cathodal current may selectively inhibit salty and bitter-salty tastes for which proximal stimuli are cations.

There is considerable evidence of interactions between adenosine A2A receptors and dopamine D2 receptors in striatal areas, and antagonists of the A2A receptor have been shown to reverse the motor effects of DA antagonists in animal models. The D2 antagonist haloperidol produces parkinsonism in humans, and also induces motor effects in rats, such as suppression of locomotion. The present experiments were conducted to study the ability of the adenosine A2A antagonist MSX-3 to reverse the locomotor effects of acute or subchronic administration of haloperidol in rats. Systemic (i.p.) injections of MSX-3 (2.5-10.0 mg/kg) were capable of attenuating the suppression of locomotion induced by either acute or repeated (i.e., 14 day) administration of 0.5 mg/kg haloperidol. Bilateral infusions of MSX-3 directly into the nucleus accumbens core (2.5 microg or 5.0 microg in 0.5 microl per side) produced a dose-related increase in locomotor activity in rats treated with 0.5 mg/kg haloperidol either acutely or repeatedly. There were no overall significant effects of MSX-3 infused directly into the dorsomedial nucleus accumbens shell or the ventrolateral neostriatum. These results indicate that antagonism of adenosine A2A receptors can attenuate the locomotor suppression produced by DA antagonism, and that this effect may be at least partially mediated by A2A receptors in the nucleus accumbens core. These studies suggest that adenosine and dopamine systems interact to modulate the locomotor and behavioral activation functions of nucleus accumbens core.

POPULATION: Population: Illinois Caucasian (n=117), Illinois African American (n=218), and Illinois Hispanic (n=68).

Objective: To investigate the relationship between lifetime mood and psychotic spectrum features in patients with borderline personality disorder (BPD). Method: The study sample consisted of BPD patients with (n = 39, BPD-M) or without (n = 21, BPD-noM) lifetime mood disorders. The diagnostic assessment was conducted with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). The diagnosis of BPD was made clinically and then confirmed by Gunderson's diagnostic interview for borderlines. Subjects were also administered the Structured Clinical Interview for Psychotic Spectrum (SCI-PSY) and the Mood Spectrum self-report questionnaire (MOODS-SR). Results: BPD-M had significantly higher scores than BPD-noM on the ‘lifetime’ mood spectrum subdomains ‘depressive mood’ and ‘depressive cognition’. The two groups did not differ on the scores of psychotic spectrum except for higher ‘hypertrophic self-esteem’ scores in BPD-noM. In BPD-noM both the depressive and the manic-hypomanic component of mood spectrum were significantly correlated with the ‘delusion’ subdomain of the psychotic spectrum. The depressive component was correlated with ‘depersonalization/derealization’ and the manic-hypomanic component was correlated with ‘hypertrophic self-esteem’. In BPD-M, the manic-hypomanic component of mood spectrum was correlated with different subdomains of the psychotic spectrum: ‘hypertrophic self-esteem’, ‘self-reference’, ‘interpretive attitude’, ‘anger/overreactivity, ‘unusual and odd thoughts’, ‘illusions’, ‘delusions’, ‘hallucinations’ and ‘catatonia’. The depressive component of mood spectrum was ‘uncorrelated’ with the subdomains of the psychotic spectrum. Conclusions: Our data support the hypothesis that ‘lifetime’ manic-hypomanic mood dysregulations are correlated with psychotic spectrum features in borderline patients. The assessment of these spectrum features in borderline patients may be useful to inform treatment choices.

Variation in intake of sweet and bitter solutions by inbred strains of laboratory mice has helped identify genes related to taste behaviors; but similar information is not available for golden hamsters (Mesocricetus auratus ), a species used much in taste research. Thus, 6-hour, 1-bottle intake by water-replete hamsters of 7 inbred strains was measured for water and 2 concentrations of sucrose, maltose, D-phenylalanine (D-Phe), and sodium saccharin, which are sweet; and quinine.HCl, L-phenylalanine (L-Phe), caffeine, and sucrose octaacetate (SOA), which are bitter to humans. Difference scores (DIF), calculated as solution intake minus mean baseline water intake (mL) for each animal, were evaluated by analysis of variance. Compared to ACN, CN, APA, APG, and CBN, five strains with similar DIF for all compounds, GN, an ancestral strain of ACNT, and ACNT preferred sucrose, caffeine, and SOA more strongly; ACNT also preferred saccharin and maltose more strongly and rejected quinine more strongly. Narrow sense heritabilities for the 6 compounds for which strain differences were revealed ranged from 0.31 to 0.57. Genetic correlations indicated the strain variations in intake of sucrose, saccharin, SOA, and caffeine were coupled; a statistical association with several possible interpretations. Intakes of the two amino acids, preferred D-Phe and aversive L-Phe, did not reveal strain differences, and heritability ranged from 0.13 to 0.23 for the two optical isomers. Thus, although, compared to mice, genetic variation in laboratory hamsters may be small, genetic differences that influence taste behaviors in existing strains may help identify relevant genes.

The diverse chemical structures of stimuli that are bitter to humans suggest a need for multiple bitter receptors. Reactions of golden hamsters (Mesocricetus auratus) to 1 mM quinine hydrochloride, 3 mM denatonium benzoate, 180 mM magnesium sulfate, 30-100 mM caffeine, and 1-1.5 mM sucrose octaacetate (SOA) were studied to address whether there are multiple sensations elicited by bitter stimuli. Methods included behavioral generalization of LiCl-induced conditioned taste aversions (CTAs), intake preference tests, and electrophysiological recordings from the chorda tympani (CT) nerve. The five compounds, all bitter to humans, were all innately aversive to hamsters. CTA for the ionic quinine.HCl, denatonium benzoate, and MgSO(4) mutually cross-generalized and these ionic compounds were effective CT stimuli. Yet, the hamsters were much less sensitive to denatonium than humans, requiring a 100,000 times higher concentration for detection. CTA for nonionic caffeine and SOA did not cross-generalize to quinine or the other two ionic stimuli and these nonionic compounds were not effective CT stimuli. SOA and caffeine may elicit aversive reflexes or systemic reactions rather than taste sensations in the animals. Thus, the three ionic and two nonionic compounds form separate aversive stimulus classes in hamsters, neither of which appears to be a close homologue of the human bitter taste.

This paper reports on the acceptability, reliability and validity of the Structured Clinical Interview for the Spectrum of Substance Use (SCI‐SUBS), a new instrument exploring the interactive pathway between substance abuse and psychiatric disorders. Psychiatric outpatients with (n = 21) and without (n = 32) substance abuse comorbidity according to the DSM‐IV, non‐psychiatric subjects with opioid dependence (OD, n = 14) and normal controls (n = 33) were assessed with the SCI‐SUBS. The presence or absence of psychiatric disorders was determined with the Structured Clinical Interview for DSM IV (SCID). The SCI‐SUBS was well accepted by participants. The internal consistency of the domains was satisfactory (between 0.64 and 0.93). Domain scores of OD subjects were significantly higher than those of controls and of psychiatric patients without substance abuse. The cut‐off point on the SCI‐SUBS total score at which there was optimal discrimination between the presence and the absence of a DSM‐IV diagnosis of substance abuse was 45. The pilot version of the SCI‐SUBS has satisfactory internal consistency and construct validity. Copyright © 2003 Whurr Publishers Ltd.

The clinical course of inflammatory bowel disease (IBD) in dogs is characterized by spontaneous exacerbations and remissions, which makes assessment of disease burden difficult. The objectives of this study were to develop a scoring system for evaluation of canine IBD activity and to validate this scoring method by correlating it to objective laboratory and histologic indices of intestinal inflammation. Fifty-eight dogs with IBD were evaluated prospectively and compared to 9 disease-free control dogs. Clinical disease activity was quantified by a simple scoring system, the canine IBD activity index (CIBDAI), and compared to serum concentrations of C-reactive protein (CRP), haptoglobin (HAP), alpha-acid glycoprotein (AGP), and serum amyloid A (SAA), as well as histology scores derived from endoscopic biopsy specimens. Forty-six dogs were available for a reevaluation of the CIBDAI, CRP HAP, and AGP, and 34 dogs had repeat analysis of SAA performed after medical therapy. Serum concentrations of CRP were significantly (P.02) increased in dogs with CIBDAI scoresor = 5 (mild disease activity or greater) compared to controls. Among IBD dogs, the CIBDAI showed good correlation (r = 0.82, P.0001) to both histology and HAP scores, but CRP also was a strong co-correlate of disease activity. The IBD dogs showed significantly (P.0001) decreased CIBDAI and CRP values but significantly (P.0001) increased HAP concentrations after medical therapy compared to pretreatment values. We conclude that the CIBDAI is a reliable measure of inflammatory activity in canine IBD and that CRP is suitable for laboratory evaluation of the effect of therapy in these patients.

There is an accumulating body of evidence indicating that soluble major histocompatibility complex (sMHC) molecules have donor-specific immunosuppressive properties. One classic, but still unproven, theory is that production of sMHC by liver transplants induces a potent immunosuppressive effect. To mimic this possible effect, we have developed a replication deficient adenovirus (Ad-RQ) to express high levels of donor sMHC class I molecules (sRT1.A(a)) in the liver. Ad-RQ produced sRT1.A(a) was measured by enzyme-linked immunosorbent assay (ELISA) after in vitro infection of Lewis (RT1(l)) hepatocytes, and in vivo following intravenous virus injection into Lewis rats. Results indicated high sRT1.A(a) expression in Lewis hepatocyte cultures and, in vivo, high expression was also demonstrated and maintained for at least 1 week. A strong immunosuppressive potential of sMHC in vivo was revealed by prolongation of cardiac (ACI, RT1(a)) heart allograft survival in high-responder Lewis rat recipients treated with Ad-RQ alone. Furthermore, limiting dilution cytotoxic T-lymphocyte precursor (CTLp) analysis of lymphocytes from Ad-RQ-treated Lewis recipients receiving an ACI heart transplant indicated a marked decrease in antidonor CTLp frequency. In conclusion, our results demonstrate that viral vectors can be used effectively to express high levels of sMHC molecules, and their immunosuppressive effect, without concurrent immunosuppression, is sufficiently potent to prolong heart transplant survival.

Surveys show that the majority of firms provide merit pay to outstanding employees. Despite the widespread use of merit pay programs, there is no consensus as to their effectiveness. While some plans have been successful in motivating employees to achieve higher performance, others have caused employees' dissatisfaction and discouragement. One previously unexplored area in the implementation of merit pay systems is the effect of the decision-maker's prior involvement with the employee on the decision to grant merit. The purpose of this paper was to examine whether hiring an employee leads to larger merit allocations despite evidence that the standards for merit were not met. 101 accounting students participated to assess the influence of hiring on subsequent merit allocations. Analysis indicated that prior involvement does bias ensuing merit decisions.

Chlorhexidine, a bis-cationic biguanide antiseptic, greatly reduces the perceived intensity of the salty prototype sodium chloride and may prove to be an important probe of mechanisms that underlie the human salty taste quality. Chlorhexidine, which tastes bitter, also reduces quinine hydrochloride taste intensity, but neither sweet sucrose nor sour citric acid is affected. Perceptual intensity rating and quality identification were measured for human subjects before and for 30 min following treatment with 1.34 mM chlorhexidine gluconate. In one experiment, test stimuli were the taste-quality prototypes; in a second experiment, stimuli were series of sodium, halide and sulfate salts. Experiment 1 showed a single 3-min chlorhexidine treatment resulted in reductions in taste intensity that persisted for at least 30 min. Experiment 2 showed a single 2-min chlorhexidine treatment reduced perceptual intensities of halide and sulfate salts except those with divalent cations. Chlorhexidine impaired identification of the salty quality and produced a bitter quality in nonbitter salts and impaired identification of the bitter quality of quinine, but not bitter salts. The specific effect of chlorhexidine on the bitterness of quinine suggests it may bind to the same receptor as quinine. The ability of chlorhexidine to specifically disrupt saltiness of a wide range of salts is consistent with proposed peripheral transduction mechanisms for the salty quality that involve transepithelial ion transport.

Burning mouth syndrome (BMS) is an oral pain disorder occurring primarily in post-menopausal women and is frequently accompanied by taste complaints. This association of symptoms suggests an interaction between the mechanisms of nociception and gustation, two senses with strong hedonic components. Seventy-three patients of the Taste and Smell Clinic at the University of Connecticut Health Center who reported experiencing 'unexplained oral burning' were evaluated for taste function. Both intensity ratings and quality identifications were measured for a concentration series of sucrose ('sweet'), NaCl ('salty'), citric acid ('sour') and quinine-HCl ('bitter'). The 57 women with BMS gave lower intensity ratings to NaCl and sucrose than comparably aged, same sex controls. Concentrations of NaCl and sucrose >0.10 M were most affected; concentrations of sucrose and NaCl

To examine the clinical and genetic heterogeneity of autosomal dominant optic atrophy among two unrelated central Illinois families.Forty-three individuals from two pedigrees had complete eye examinations. Linkage analysis was performed with microsatellite markers from the region 3q28-29.Visual acuity in 21 affected individuals ranged from 20/25 to 20/800. Vision loss was more severe in males than females (P = 0.02). Color vision testing revealed generalized dyschromatopsia. Both visual acuity and color vision deteriorated with age. Linkage was established to chromosome 3q28-29 (LODmax = 4.68 for D3S2305).Autosomal dominant optic atrophy linked to chromosome 3q28-29 shows intrafamilial phenotypic variation as well as sex-influenced severity in two Midwestern families.

Behavioral studies suggest that there are significant differences in the taste systems of the inbred mouse (Mus musculus) strains: C57BL/6J (B6) and DBA/2J (D2). In an attempt to understand the biological basis of the behavioral differences, we recorded whole-nerve chorda tympani responses to taste solutions and compared the results to intake of similar solutions in nondeprived mice. Stimuli included a test series composed of 0.1 M sodium chloride, 0.3 M sucrose, 10 mM sodium saccharin, 3 mM hydrochloric acid, and 3 mM quinine hydrochloride, as well as concentration series for the same substances. Neural activity of the chorda tympani that was evoked by sucrose, saccharin, or NaCl was greater in B6 than D2 mice; and neural threshold for sucrose was lower in B6 mice, but neural thresholds for HCl and quinine were lower in D2 mice. B6 mice drank more sucrose and saccharin but less quinine than D2 mice; thus, sucrose and saccharin preference were positively correlated, but NaCl and quinine aversiveness were negatively correlated with the chorda tympani results. Nonetheless, genes involved in the structuring of taste receptors and/or the chordae tympani, which transduce taste stimuli having diverse perceptual qualities, differ for the two mouse strains.

Charcot-Marie-Tooth disease (CMT) with deafness is clinically distinct among the genetically heterogeneous group of CMT disorders. Molecular studies in a large family with autosomal dominant CMT and deafness have not been reported. The present molecular study involves a family with progressive features of CMT and deafness, originally reported by Kousseff et al. Genetic analysis of 70 individuals (31 affected, 28 unaffected, and 11 spouses) revealed linkage to markers on chromosome 17p11.2-p12, with a maximum LOD score of 9.01 for marker D17S1357 at a recombination fraction of .03. Haplotype analysis placed the CMT-deafness locus between markers D17S839 and D17S122, a approximately 0.6-Mb interval. This critical region lies within the CMT type 1A duplication region and excludes MYO15, a gene coding an unconventional myosin that causes a form of autosomal recessive deafness called DFNB3. Affected individuals from this family do not have the common 1.5-Mb duplication of CMT type 1A. Direct sequencing of the candidate peripheral myelin protein 22 (PMP22) gene detected a unique G-->C transversion in the heterozygous state in all affected individuals, at position 248 in coding exon 3, predicted to result in an Ala67Pro substitution in the second transmembrane domain of PMP22.

Molecules of diverse chemical structure are sweet to humans and several lines of evidence (genetic, physiological, behavioral) suggest that there may be distinct sweet perceptual qualities. To address how many perceptual categories these molecules elicit in hamsters (Mesocricetus auratus), we studied patterns of generalization of conditioned taste aversions for seven sweeteners: 100 mM sucrose, 320 mM maltose, 32 mM D-phenylalanine, 3.2 mM sodium saccharin, 16 mM calcium cyclamate, 10 mM dulcin and 32 mM sodium m-nitrobenzene sulfonate. Each stimulus was preferred versus water in two-bottle intake tests and stimulated the chorda tympani nerve. For each of seven experimental groups the conditional stimulus (CS) was a sweetener and for the control group the CS was water. Apomorphine.HCl was injected i.p. after a CS was sampled and, after recovery, test stimuli (TS) were presented for 1 h daily. The intake (ml) of each TS consumed by experimental animals was compared with mean TS intake by the control group. Learned aversions for 18/21 stimulus pairs cross-generalized, resulting in a single cluster of generalization patterns for the seven stimuli. Cross-generalization failures (maltose-cyclamate, maltose-sucrose, cyclamate-NaNBS) may be the consequence of particula r stimulus features (e.g. salience, cation taste), rather than the absence of a 'sucrose-like' quality. The results are consistent with a single hamster perceptual quality for a diverse set of chemical structures that are sweet to humans.

This prospective study evaluated heterotopic ossification prophylaxis with indomethacin for 14 days in 201 consecutive patients undergoing total hip arthroplasty. Ranitidine was administered concurrently to alleviate gastrointestinal side effects. None of the patients with mild gastrointestinal side effects (1 2%) had to suspend the prophylaxis, and no major postoperative bleeding or gastrointestinal ulcers were observed. After 12 months of follow-up, 67% of patients had no evidence of heterotopic ossification, 32% percent had grades I and 1% had grade III without clinical significance, and 0% had grade IV ossification according to BrookeKs classification. These results indicate that short-term indomethacin prophylaxis is an effective, inexpensive, and easily administrated alternative to single-dose radiotherapy for nearly all patients undergoing THA.

Hamsters show a preference for Polycose, a mixture of starch-derived glucose polymers, that is as strong as their preference for sucrose. However, in the hamster, taste aversions to Polycose may be less easily acquired than taste aversions to sucrose and the qualitative aspects of Polycose are unknown in this species. In order to examine the taste of Polycose in the hamster, we utilized a taste-aversion protocol with two conditioning trials. Animals were trained to avoid one of three different conditioning stimuli: 50 mM sucrose, 100 mM Polycose and a mixture of 50 mM sucrose with 100 mM Polycose. Control animals were conditioned with deionized water. After the second conditioning trial, generalization testing began for the three conditioning stimuli plus 3 mM citric acid, 300 mM KCI and 30 mM NaCl. The results showed that aversions to Polycose, sucrose or the Polycose/sucrose mixture cross-generalized, demonstrating that Polycose and sucrose share a common taste percept in the hamster. None of the aversions generalized to NaCl, citric acid or KCI. In addition, comparisons among the patterns of taste generalizations indicated that the tastes of Polycose and sucrose also had distinct qualitative components. Finally, although the taste of 100 mM Polycose was more salient than the taste of 50 mM sucrose, the taste of sucrose could still be detected in a mixture with Polycose.