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Background: Recent increases in opioid use and subsequent opioid use disorder are a major public health crisis in the United States. Aims: This phase 1 randomized, placebo-controlled study investigated the safety, tolerability, and pharmacokinetics (PKs) of ASP8062, a γ-aminobutyric acid B receptor-positive allosteric modulator, with and without administration of morphine in participants who used opioids recreationally. Methods: Participants were randomly assigned (2:1) to daily dosing with ASP8062 25 mg or placebo on days 1–10. On day 10, all participants received morphine as a single oral dose of 45 mg; assessments were performed on days 11–16. The primary end point was safety, evaluated as the nature, frequency, and severity of adverse events, and end-tidal CO2 levels. PK end points were a secondary outcome measure. Results: A total of 24 participants (aged 21–54 years) received ASP8062 ( n = 16) or placebo ( n = 8). There were no deaths or serious adverse events leading to treatment discontinuation during the study. Most adverse events were mild, with numerically lower absolute number of adverse events reported with ASP8062 plus morphine versus placebo plus morphine. ASP8062 plus morphine did not increase respiratory depression, potential drug abuse- or withdrawal-related adverse events. There were no significant PK interactions. Conclusions: In this phase 1 study, we did not observe any unexpected safety signals or notable PK interactions with concomitant morphine administration. These data suggest a potentially low risk for an increase in drug abuse- or withdrawal-related adverse events or respiratory distress in participants exposed to ASP8062 and morphine.

Background: There is an unmet need for therapeutics with greater efficacy and tolerability for the treatment of opioid use disorder (OUD). ASP8062 is a novel compound with positive allosteric modulator activity on the γ-aminobutyric acid type B receptor under development for use with standard-of-care treatment for patients with OUD. Aims: To investigate the safety, tolerability, interaction potential, and pharmacokinetics (PK) of ASP8062 in combination with buprenorphine/naloxone (B/N; Suboxone®). Methods: In this phase 1, randomized, double-masked, placebo-controlled study, patients with OUD began B/N (titrated to 16/4 mg/day) treatment upon enrollment (induction, Days 1–4; maintenance, Days 5–18; downward titration, Days 19–26; and discharge, Day 27). On Day 12, patients received a single dose of ASP8062 60 mg or placebo with B/N and underwent safety and PK assessments. Primary endpoints included frequency and severity of treatment-emergent adverse events (TEAEs), clinical laboratory tests, respiratory depression, and suicidal ideation. Secondary endpoints investigated the impact of ASP8062 on B/N PK. Results: Eighteen patients were randomized and completed the study (ASP8062, n = 12; placebo, n = 6). With this sample size typical for phase 1 drug–drug interaction studies, ASP8062 was well tolerated; most TEAEs were mild in severity, and none led to treatment withdrawal. ASP8062 did not enhance substance use-related TEAEs, respiratory depression, or suicidal ideation and did not have a clinically significant impact on the PK of B/N. Conclusions: In this phase 1 study, ASP8062 was safe, well tolerated, and did not enhance respiratory suppression induced by buprenorphine. Trial registration: Clinicaltrials.gov identifier: NCT04447287.

This research focuses on the combustion of biomass char in fluidised beds of various particulate solids, which, under the conditions of the reaction, were either inert or capable of supplying oxygen to reactions. The latter were termed oxygen carriers. The solids used were SiO2, as an inert material, and three oxygen carriers: (1) Fe2O3 prepared from a natural pyrite ore, (2) CuO supported on mayenite, and (3) SrFeO3-δ strontium ferrite perovskite. Combustion experiments were undertaken by introducing a sample of partially-devolatilised biomass (commercial ‘bio-char’) to a hot bubbling bed (i.d. 30 mm), fluidised by a mixture of oxygen and nitrogen, then analysing the composition of the off-gas and the burnout time of the char sample. In the temperature range investigated in this work (1023 K to 1168 K), CuO and SrFeO3-δ, but not Fe2O3, thermally decomposed, releasing gaseous O2 (so-called ‘chemical looping oxygen uncoupling’, CLOU). Hence, to make the combustion conditions comparable with various oxygen carriers, all experiments were performed using a fluidising gas with a fixed partial pressure of O2, pO2, ~ 0.015 bar. Despite the same nominal pO2, the occurrence of the oxygen uncoupling reaction increased the total net amount of O2(g) available in the process, affecting external mass transfer of O2 to the char particle and accelerating its rate of combustion. The time needed to combust totally 0.1 g of biochar particles in different beds at 1168 K followed the trend CuO < SrFeO3-δ < Fe2O3 ≈ silica sand. The difference in the performance of CuO and SrFeO3-δ was ascribed to the lower oxygen availability via CLOU in the perovskite compared with the copper oxide. Interestingly, combustion in the bed of Fe2O3 particles took a similar amount of time as combustion in the inert bed of SiO2 despite iron oxide playing an active role in the process. The finding is explained by Fe2O3 reacting with the CO produced from incomplete char combustion, which results in the reduced oxide competing with char for O2(g) and effectively decreasing the local pO2.

As of December 1, 2020, when the Advisory Committee on Immunization Practices published their COVID-19 vaccine distribution and prioritization recommendations, health care workers (HCWs) and the elderly were deemed to be at greatest risk of contracting the coronavirus. Limited extant research suggests that most HCWs are willing to receive the COVID-19 vaccine, and findings from studies examining vaccine uptake in non-HCW samples also have reported high vaccination willingness. The health belief model (HBM) and the theory of planned behavior (TPB) suggest that beliefs about severity and susceptibility of disease, perceived benefits of and obstacles to vaccination, and normative beliefs of others affect vaccine uptake. Further, perceptions of safety, side effects, and demographic factors can uniquely impact COVID-19 vaccine uptake.Using a cross-sectional design, we recruited 526 participants via social media, through snowball emailing methods, and from university settings.The present findings demonstrate that 37% of participants intend to get the vaccine, and 35% reported that they might get the vaccine. No relationships among demographic factors, willingness to receive the vaccine, and level of intent were observed. However, those who reported that they would not receive the COVID-19 vaccine demonstrated fewer positive attitudes, less agreement, fewer normative views, and less anticipatory regret regarding the COVID-19 vaccine. Also, perceptions of susceptibility, severity, and barriers were associated with participants' willingness to get the COVID-19 vaccine.Our results suggest that factors related to the HBM and TPB might uniquely impact COVID-19 vaccine acceptability and could guide the crafting of interventions meant to encourage vaccine uptake. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: ASP8062 is a novel orally active GABAB receptor positive allosteric modulator in clinical development for the treatment of alcohol use disorder (AUD) and opioid use disorder (OUD). Aims: This study assessed the potential pharmacokinetic/pharmacodynamic interaction between ASP8062 and alcohol under single-dose conditions in healthy adults. Methods: A double-blind, placebo-controlled, crossover phase 1 study was conducted in which 20 subjects were randomly assigned to four treatment sequences (ASP8062 + alcohol; ASP8062 + placebo alcohol; placebo + alcohol; placebo + placebo alcohol) each consisting of four treatment periods, separated by washout periods of at least 14 days. An analysis of variance was used to assess pharmacokinetic interaction and a mixed-effects analysis of covariance was used to assess pharmacodynamic interaction. Results/outcomes: After administration of alcohol, a mild to minimal increase in plasma exposure (AUCinf and Cmax) of ASP8062 was observed, but tmax and t½ for ASP8062 remained unchanged after administration of alcohol. In contrast, ASP8062 did not affect the AUClast and Cmax of ethanol. No clinically relevant differences in cognition measurements were observed with ASP8062 compared with placebo, but there were expected impairments in psychomotor and executive function with alcohol alone. ASP8062 in combination with alcohol resulted in worse scores in cognition measurements than alcohol alone, but this potentiation was not consistent. ASP8062 administered alone was safe and well-tolerated and safety findings in subjects administered alcohol alone were not augmented when ASP8062 was administered in combination with alcohol. Conclusion/interpretation: The data support further clinical studies investigating ASP8062 in patients with AUD.

Many patients who seek treatment for chronic back pain are also at a higher risk of having comorbid anxiety- and depression-related disorders. Measures of mood and anxiety are routinely used in medical settings to screen for depression- and anxiety-related symptoms. However, factor analyses of other measures of mood and anxiety in medical settings often detect a somatization factor which, in turn, limits their discriminant validity for use across medical settings. The Inventory of Depression and Anxiety Symptoms-II (IDAS-II) is a comprehensive self-report inventory that assesses varying aspects of mood and anxiety. The purpose of this investigation is to examine the three-factor structure and validity of the IDAS-II in a chronic pain treatment-seeking sample. A total of 169 patients completed the IDAS-II and the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) upon admission. Confirmatory factor analyses were computed using the scales of the IDAS-II and zero-order correlations between the IDAS-II factors from the best-fitting model and scale scores of the MMPI-2-RF. Overall, a three-factor structure of the IDAS-II was not supported; instead, a one-factor solution fit best. Using the MMPI-2-RF as external criteria, the one-factor of the IDAS-II correlated highest with the Somatic Complaints scale and the Demoralization scale. Overall, item content on the IDAS-II shares overlap with many symptoms that patients with chronic pain likely would endorse. Discussion about implications of using mood/anxiety measures and models in medical settings that are in line with the Hierarchical Taxonomy of Psychopathology (HiTOP) are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Quiet ego is a relatively novel, increasingly studied, multi-dimensional concept characterized by a compassionate, interdependent worldview and an adaptive balance between self-interest and concern for others. Quiet ego has been associated with a range of characteristics that can promote relationship quality, responding effectively in the face of challenges, and greater well-being. However, it is currently unknown to what extent quiet ego translates across cultures and settings. The present research leverages cultural and organizational theories to evaluate the conceptual and structural validity of quiet ego for Latinx/Hispanic individuals in the U.S. and to examine relationships among quiet ego, work supervisor relationship quality, and goals in the workplace. Employed college student participants ( n = 831; nLatinx/Hispanic = 305) completed an online survey, and collected data were subjected to confirmatory factor analysis and path analysis. Findings confirmed the overall structural model of quiet ego with four primary dimensions (perspective taking, inclusive identity, detached awareness, and growth-mindedness) and indicated that this structure did not differ between Latinx/Hispanic and non-Latinx/Hispanic subsamples. Further, results cohered with the proposed model suggesting that quiet ego might facilitate relationship quality with a workplace supervisor, which, in turn could foster balanced, intrinsically motivating perceptions that one’s work goals benefit both oneself and others (mutual gain motivation). The study suggests that quiet ego may be a construct with meaning and utility in Latinx/Hispanic populations and in employment settings. However, further research is needed, and specific suggestions for future study are discussed.

Introduction/aims ASP0367, or bocidelpar sulfate, is an orally administered small molecule that potently and selectively modulates peroxisome proliferator-activated receptor δ (PPARδ) to address mitochondrial dysfunction occurring in diseases including primary mitochondrial myopathy and Duchenne muscular dystrophy. The objectives of this first-in-human trial were to evaluate the safety/tolerability, pharmacokinetics, and pharmacodynamics of ASP0367 in healthy participants. Methods In this double-blind phase 1 study, adult participants were randomized to single or multiple ascending oral doses of ASP0367 or placebo. The study duration was 1 and 14 days, respectively. Pharmacokinetic parameters under fed conditions were also evaluated. Results A total of 64 (single-dose cohort) and 37 (multiple-dose cohort) participants were included in the study. After single doses of 1 to 120 mg, ASP0367 was rapidly absorbed, with median time to maximum plasma concentration (tmax ) of 1.50 to 2.24 hours under fasting conditions; ASP0367 concentrations declined in a multiphasic manner after reaching maximum plasma concentration. Under fed conditions, tmax was delayed 1.7 hours. After multiple once-daily doses, mean half-life of ASP0367 10 to 75 mg ranged from 14.1 to 17.5 hours; steady state was reached after 4 days. Negligible accumulation was observed after repeated dosing. No participants receiving ASP0367 discontinued treatment, and all treatment-emergent adverse events were mild to moderate in severity; none were considered drug-related. No clinically significant changes were observed on laboratory or electrocardiographic evaluation. Treatment- and dose-dependent upregulation of six PPARδ target genes was observed with single and multiple doses of ASP0367. Discussion ASP0367, or bocidelpar sulfate, was well tolerated; rapid absorption, roughly dose-proportional bioavailability, and effects on PPARδ target genes were demonstrated in healthy adult participants.

Eating disorders are prevalent among college student populations. Although previous iterations of the instrument did not include specific measurement of eating pathology, the Minnesota multiphasic personality inventory-3 (MMPI-3) now includes a specific scale (i.e., Eating Concerns [EAT]) to assess problematic eating behaviors. The current study examined the MMPI-3 assessment of eating pathology among 249 undergraduate women. A pattern emerged where symptoms of internalizing psychopathology on the MMPI-3 were generally associated with symptoms of eating disorder. However, the newly included EAT scale demonstrated the strongest associations with most areas of eating dysfunction. Further, hierarchical regression analyses suggested that the EAT scale added substantial incremental predictive utility (up to 23%) over other MMPI-3 scales combined in assessing eating pathology. Classification accuracy statistics yielded high sensitivity and specificity coefficients when predicting eating disorder risk at an EAT scale score cutoff of 75 T or higher. These findings support the use of the MMPI-3 in assessing eating pathology in college women, although its performance with men and with women not of college age remains to be studied.

The Attitudes Toward Persons with Obesity (ATOP) scale is widely used to assess stigmatization toward persons with obesity. The measure has previously been suggested to assess three facets—self-esteem, personality, and social difficulties—however, psychometric support for this has been inconsistent and warrants further study if the measure intends to be scored this way. Explore and confirm the factor structure of the ATOP in people assessed prior to bariatric surgery and reassessed 1 year postoperatively Midwestern hospital in the USA. Three-hundred sixteen people who were seeking bariatric surgery were assessed preoperatively, and 161 of those people were reassessed 1 year after surgery with a battery of measures including the ATOP. Exploratory factor analysis (EFA) was performed on ATOP data from a random split-half of people before surgery, and confirmatory factor analysis (CFA) was performed on the second randomly selected half. With the postoperative sample, a CFA was performed, testing the best-fitting model from the preoperative CFA findings. The EFA suggested a two-factor structure interpreted as self-esteem and personality/social difficulties. This structure was supported by CFA performed on the second randomly selected half of people at preoperative assessment and by CFA performed on people 1 year following surgery. Tests of measurement invariance suggested that the two-factor structure was similar at both time points. Only two factors for the ATOP were empirically supported in the current sample (self-esteem and personality/social difficulties), which is slightly different from the three factors that were originally proposed when the measure was developed. This factor structure is supported both prior to bariatric surgery and 1 year after bariatric surgery.

Presurgical psychological assessment of bariatric surgery candidates aims to identify psychosocial risk factors and provide treatment recommendations to facilitate optimal outcomes. Such assessment typically includes psychometric testing and a clinical interview. The Minnesota Multiphasic Personality Inventory (MMPI) has been commonly used as a broadband measure to assess a number of psychosocial domains in bariatric clinics. The newest version of the MMPI, the MMPI-3, was recently released. This study sought to (1) establish whether the MMPI-3 is comparable to the MMPI-2-RF in a sample of patients seeking bariatric surgery, (2) report reliability data for all MMPI-3 scale scores in this sample, and (3) explore associations between commonly used self-report symptom measures and substantive scales of the MMPI-3 to ascertain convergent and discriminant validity patterns. Six hundred and thirty-five presurgical patients completed the MMPI-3 in addition to the Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), and Eating Disorder Examination-Questionnaire (EDE-Q). The majority (79.1%) of the sample was female, 65.5% was white, and 26.6% was Black. Scores on most of the MMPI-3 Emotional/Internalizing Dysfunction scales were meaningfully associated with the PHQ-9, GAD-7, and most EDE-Q subscales (except for Restraint). Meaningful discriminant patterns were observed as well. We conclude that the substantive scales of the MMPI-3 are reliable, comparable to their MMPI-2-RF counterparts, and evidence good convergent validity with extra-test measures assessing depression, anxiety, alcohol use, and eating disorder psychopathology in a preoperative bariatric sample.

Photothermal therapy (PTT) is a promising treatment option for diseases, including cancer, arthritis, and periodontitis. Typical photothermal agents (PTAs) absorb light in the near-infrared (NIR)-I region of 650-900 nm with a predominant focus around 800 nm, as these wavelengths are minimally absorbed by water and blood in the tissue. Recently, interest has grown in developing nanomaterials that offer more efficient photothermal conversion and that can be excited by light close to or within the NIR-II window of 1000-1700 nm, which offers less absorption by melanin. Herein, we report on the development of 5,5-diphenyl isocorrole (

Chronic pain has become a significant medical issue. The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) is a broadband psychological test that has been validated for use across various medical settings and can aid in the assessment and treatment planning of chronic pain. In the current investigation, it was hypothesized that the somatic complaints scales of the MMPI-2-RF would demonstrate good convergent validity from a structured psychodiagnostic interview and other measures of pain and somatization, and lack gender bias. Patients (n = 200) who produced valid MMPI-2-RFs in an outpatient chronic pain clinic were included in the study. Patients were also administered the Modified Somatic Perception Questionnaire (MSPQ), Pain Disability Index (PDI), and the Structured Clinical Interview for DSM-IV-TR (SCID). Zero-order and partial correlations (controlling for gender) were calculated between MMPI-2-RF scale scores and other criteria. Stepdown hierarchical regression analyses were used to detect bias. By and large, higher scale scores on the somatic/cognitive scales of the MMPI-2-RF were modestly or substantially correlated with MSPQ scores, PDI scores, and SCID Somatization symptom count, even after controlling for gender. Regression analyses suggested that the MMPI-2-RF scale scores were not biased as a function of gender. These findings support the validity of specific MMPI-2-RF scales to help identify somatization and psychosocial functioning among patients with chronic pain. Identification of somatization early within the course of treatment of chronic pain may help focus treatment targets, including referrals for psychological interventions such as cognitive behavior therapy for chronic pain.

A considerable number of post-bariatric surgery patients report problematic eating behaviors (PEBs) and/or eating disorders (EDs). Examining psychosocial variables associated with ED symptoms may identify targets for postoperative interventions to reduce these behaviors and improve surgical outcomes. A total of 161 participants completed the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) and the Eating Disorder Examination-Questionnaire (EDE-Q). Participants were classified into ED risk or no ED risk groups and subjective binge eating (SBE) or no SBE groups. Independent-sample t tests were computed to examine mean differences in total weight loss (%TWL) and MMPI-2-RF scale scores between the ED groups. Relative Risk Ratios (RRRs) were computed to determine which MMPI-2-RF scales were associated with increased risk of ED group membership. The ED risk group lost significantly less weight (19.36% TWL) than the no ED risk group (25.18% TWL). The SBE group lost significantly less weight (17.98% TWL) than the no SBE group (25.57% TWL). Participants in the ED groups scored significantly higher on internalizing and externalizing MMPI-2-RF scales than the no ED groups. These scales were associated with increased risk (1.55–2.55 times the risk) of being classified into the ED groups. Patients who experienced postoperative ED symptoms lost significantly less weight than patients without ED symptoms. Postoperative ED symptoms are related to, and may be impacted by, higher levels of internalizing and externalizing dysfunction after surgery. Postoperative assessment of and interventions targeting psychosocial dysfunction could decrease ED symptoms. III: Evidence obtained from well-designed cohort or case–control analytic studies.

Rationale Previous research suggests that sleep polysomnography and EEG endpoints can be used to assess GABAergic activity; however, the impact of GABAB receptor positive allosteric modulators on sleep endpoints remains unclear. Objectives This phase 1 study compared a single dose of ASP8062 (35 mg or 70 mg), a GABAB receptor positive allosteric modulator, with placebo and paroxetine (40 mg). Methods Healthy adult volunteers were randomized to four treatments (35 mg ASP8062, 70 mg ASP8062, paroxetine 40 mg, or matching placebo), each separated by a 14-day washout. Primary endpoints obtained by polysomnography were time in stage N3 or SWS and time in rapid eye movement (REM) sleep. Secondary endpoints included impact on sleep stages and electroencephalography parameters, pharmacokinetics, nighttime growth hormone (GH), and safety/tolerability. Results In 20 randomized volunteers, ASP8062 led to a significant and seemingly dose-dependent increase in SWS over the entire night; this increase was mainly observed during the first third of the night. ASP8062 did not impact time in REM sleep. Paroxetine had no effect on SWS but produced a significant reduction in time spent in REM sleep. A dose-dependent trend in increased GH release was also observed with ASP8062. Headache and nausea were the most commonly reported treatment-emergent adverse events (TEAEs) for ASP8062; most TEAEs were mild in severity. Conclusions Single-dose ASP8062 (35 and 70 mg) appeared to result in CNS penetration and enhanced GABAergic activity as measured by increases in slow-wave sleep and growth hormone release.

Purpose ASP0819 is a novel, non-opioid KCa3.1 channel opener that reverses abnormal nerve firing of primary sensory afferent nerves. Currently available treatments for fibromyalgia provide only modest relief and are accompanied by a host of adverse side effects. Patients and Methods In this phase 2a, double-blind trial (NCT03056690), adults meeting fibromyalgia diagnostic criteria were randomized 1:1 to receive either 15 mg/day of oral ASP0819 (n=91) or placebo (n=95). The primary endpoint was the change from baseline to Week 8 in the mean daily average pain score. Changes in the Fibromyalgia Impact Questionnaire Revised (FIQR) symptoms, function, and overall impact subscales, as well as changes in the patients’ global impression of change, were secondary endpoints; treatment effects on FIQR total score and impact on sleep were exploratory analyses. Results There was no statistically significant difference between ASP0819 and placebo for the primary endpoint (P=0.086); however, ASP0819 versus placebo significantly improved daily average pain at Weeks 2, 6, and 7 (all P

ASP4345, a novel dopamine D1 receptor positive allosteric modulator, is being evaluated for the treatment of cognitive impairment associated with schizophrenia (CIAS). This phase 1 multiple ascending-dose study (NCT02720263) assessed the safety, tolerability, and pharmacodynamics of ASP4345 in patients with schizophrenia/schizoaffective disorder. Pharmacodynamic assessments were Cogstate cognitive tests and electrophysiological biomarkers, including gamma-band power and phase synchronization in response to 40-Hz auditory steady-state stimulation, as well as mismatch negativity (MMN) and P3a event-related potentials. The sample size determination was based on standard practice in assessing safety and tolerability of a new chemical entity. Data were summarized by conversion of this data into effect sizes using descriptive and inferential statistics. A total of 36 randomized patients received ASP4345 (3, 15, 50, and 150 mg; n = 9 each dose) and 12 patients received placebo. Patients in the ASP4345 group experienced 73 treatment-emergent adverse events (TEAEs) and 34 TEAEs were reported for the placebo group. The most common TEAEs were headache and somnolence and nearly all TEAEs were mild in severity. No changes in mood or self-reports of suicidal ideation/behavior were observed. Improvements in performance on cognitive tests were noted, which suggests a potential improvement in psychomotor function and visual attention. Furthermore, positive changes in neurophysiological biomarkers (auditory steady-state response [ASSR] and MMN) suggest improvement in information processing. The findings need to be confirmed in studies with a larger patient population. Nonetheless, the trends in safety and pharmacodynamic data support further clinical development of ASP4345 for the treatment of CIAS.

Eating pathology is common pre-operatively and continues to be prevalent following bariatric surgery. A new version of the Minnesota Multiphasic Personality Inventory (MMPI), the MMPI-3, contains a new scale called Eating Concerns (EAT) that aims to assess problematic eating behaviors. The current investigation seeks to establish preliminary convergent validity of the MMPI-3 EAT scale in a postoperative bariatric surgery sample. Thirty-eight consecutive participants took the MMPI-3 and the Eating Disorder Examination–Questionnaire (EDE-Q). Higher MMPI-3 EAT scale scores were meaningfully associated with %Weight Regain (r = .37) and scale scores on the EDE-Q [Eating Concerns (r = .67), Weight Concerns (r = .39), Shape Concerns (r = .54), and the EDE total score (r = .59)]. Initial examination of the EAT Specific Problem Scale of the MMPI-3 yields good clinical utility in assessing eating pathology in a postoperative bariatric surgery sample.

Mental health professionals routinely assess psychosocial risk factors prior to bariatric surgery to help identify factors that may impede surgical outcomes. Data regarding longer-term psychosocial functioning postoperatively are needed. Assess the psychosocial functioning of patients who obtained bariatric surgery approximately 6 years ago. A total of 161 patients consented to participate in the outcome study. Participants were compensated for their time and participation. Participants were weighed by the research/clinical staff and asked to complete a battery of self-report measures, including the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF). Other measures targeted adherence, eating behaviors/body image, alcohol use, and quality of life. Postoperative MMPI-2-RF scores indicate psychosocial functioning is largely similar to previously published pre-surgical functioning data. Six-year weight loss outcomes were lower than previous studies reported for a similar postoperative time period (mean %total weight loss = 22.98%; standard deviation = 11.71), though quality of life scores were relatively high. Postoperative MMPI-2-RF scale scores were associated with poorer psychosocial functioning, reduced adherence, greater eating behaviors/body image concerns, greater alcohol use severity, lower quality of life, and less overall weight loss. Psychological dysfunction 6 years after surgery is associated with various adverse outcomes. Ongoing, postoperative treatment may result in better long-term functioning for patients.

ASP8062 is an orally active γ-amino-butyric acid type B (GABAB ) receptor positive allosteric modulator currently in phase 2 development. Safety and pharmacokinetic (PK) profiles of ASP8062 were evaluated in 2 studies in healthy subjects. The first study (a first-in-human study) evaluated single ascending doses (SAD) of ASP8062. The second study was composed of 2 parts: part 1 evaluated multiple ascending doses (MAD) of ASP8062 for 14 days, and part 2 was a single-dose arm to assess the PK of ASP8062 in cerebrospinal fluid (CSF). Fifty-six men (SAD) and 56 subjects (24 women and 32 men; MAD) were enrolled. Across the SAD dosing range, area under the concentration-time curve was dose proportional; increases in maximum plasma concentration appeared linear but were slightly less than dose proportional. Time to maximal concentration and half-life were 1-4 hours and ∼40-50 hours, respectively; no food effect was observed. ASP8062 PK properties at steady state were similar to those following a single dose. Steady state was achieved by ∼day 9 with ∼2-fold accumulation, and ASP8062 was detected in CSF. ASP8062 was well tolerated; no clear evidence of ASP8062's effects on safety, cognition, drug withdrawal, or suicidal ideation/behavior was observed. These data support the development of ASP8062 in indications where the GABAB receptor is a target.

Healthcare in the United States has increasingly benefited from the adoption of multidisciplinary providers. Many multidisciplinary teams include psychologists who often conduct psychological and personality assessments in their practice. This special section highlights areas of personality and psychological assessment in applied healthcare contexts. Nghiem and colleagues review the psychometric performance of various personality and psychopathology instruments and provide recommendations for the assessment of solid organ transplant evaluations. Gottschling and colleagues present a culturally adapted screener for anxiety-related symptoms in geriatric adults that can easily be administered in various healthcare settings. Perry and colleagues provide a rationale and method for including a brief personality assessment for patients with cancer. McCord presents a broadband screener, the Multidimensional Behavioral Health Screen (MBHS), that assesses 9 components of psychopathology. Mitchell and colleagues provide evidence for using the MBHS in primary care clinics as an alternative to the Patient Health Questionnaire-9. This special section provides evidence-based information regarding personality and psychological assessments that will likely be useful in varied healthcare contexts.

Psychopathology among liver and kidney transplant patients is prevalent. Although pre-surgical psychological evaluations are routinely conducted, understanding which specific psychological test to use is under-developed. The purpose of this review is to examine the psychometric properties of broadband and narrowband psychological measures in pre-surgical liver and kidney transplant evaluations. Overall, there is a paucity of research in this domain that hamper abilities to make clear recommendations on what to use alongside a clinical interview. This review highlights the need for additional research examining instruments that may predict patients' successful recovery from transplant surgery. Despite the scarcity of research, instruments that appear to be useful in this population include the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), the Personality Assessment Inventory (PAI), the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT), and the Transplant Evaluation and Rating Scale (TERS).

The Minnesota Multiphasic Personality Inventory (MMPI) family of instruments has been commonly used for the evaluation of patients seeking surgical intervention for back pain. A new version of the MMPI, the Minnesota Multiphasic Personality Inventory-3 (MMPI-3), has been released with updated normative data, expanded and revised item content, and updated scales. The purpose of this investigation is to report reliability and validity findings for MMPI-3 scale scores of patients seeking spine surgery. Using a sample of 761 spine surgery candidates (390 men and 371 women), descriptive data, reliability and standard error of measurement, and zero-order correlations using external criteria (self-report and information gathered from a medical record review/clinical interview) were calculated. By and large, men and women produced MMPI-3 scale scores that were similar with a few exceptions. Many reliability estimates and standard errors of measurement were replicable compared to those reported for the MMPI-3 normative sample for scales that yielded adequate range. The scale scores of the MMPI-3 also yielded evidence of good convergent and discriminant validity when correlated with external criteria. Indeed, MMPI-3 scale scores accounted for 2%-15% of incremental variance in data obtained via the clinical interview and medical chart, once other self-report measures were accounted for. Overall, many of the MMPI-3 scale scores used in spine surgery evaluations appear to be reliable and valid. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

ASP0367, or bocidelpar sulfate, is an orally administered small molecule that potently and selectively modulates peroxisome proliferator-activated receptor δ (PPARδ) to address mitochondrial dysfunction occurring in diseases including primary mitochondrial myopathy and Duchenne muscular dystrophy. The objectives of this first-in-human trial were to evaluate the safety/tolerability, pharmacokinetics, and pharmacodynamics of ASP0367 in healthy participants.In this double-blind phase 1 study, adult participants were randomized to single or multiple ascending oral doses of ASP0367 or placebo. The study duration was 1 and 14 days, respectively. Pharmacokinetic parameters under fed conditions were also evaluated.A total of 64 (single-dose cohort) and 37 (multiple-dose cohort) participants were included in the study. After single doses of 1 to 120 mg, ASP0367 was rapidly absorbed, with median time to maximum plasma concentration (tASP0367, or bocidelpar sulfate, was well tolerated; rapid absorption, roughly dose-proportional bioavailability, and effects on PPARδ target genes were demonstrated in healthy adult participants.

Presurgical psychological evaluations (PPEs) are becoming an established component of the surgical process, though methods of conducting PPEs are variable. There is a lack of clarity about the goals of PPEs, the types of information that should be included, and the process for integrating information and making recommendations to the referring physicians/surgeons. This review proposes an empirically supported model for PPEs that is systematic, but flexible enough to be utilized across the broad range of surgical evaluations. This five-step method is termed the Risk Identification and Mitigation (RIM) model and is discussed in detail. The RIM model presented in this review can both serve as a structure to be utilized in under-researched PPE areas and as a stimulus for future empirical investigations.

History of the study, taxonomy, and distribution of the actinoceratid genus Lambeoceras Foerste are discussed. Three new nominal species and one form in open nomenclature from the Upper Ordovician (Nirunda horizon, Katian Stage) of Central Siberia (Podkamennaya Tunguska River basin) are described.

The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme converts cortisone to cortisol and participates in the regulation of glucocorticoid levels in tissues. 11β-HSD1 is expressed in the liver, kidney, adipose tissue, placenta, and brain. 11β-HSD1 is a target for treatment of depression, anxiety, posttraumatic stress disorder, and also against age-related cognitive function and memory loss. In this study, we evaluated the radiotracer 11C-AS2471907 (3-(2-chlorophenyl)-4-(methyl-11 C)-5-[2-[2,4,6-trifluorophenoxy]propan-2-yl]-4H-1,2,4-triazole) to image 11β-HSD1 availability in the human brain with PET. Methods: Fifteen subjects were included in the study. All subjects underwent one 2-h scan after a bolus administration of 11C-AS2471907. Two subjects underwent an additional scan after blockade with the selective and high-affinity 11β-HSD1 inhibitor ASP3662 to evaluate 11C-AS2471907 nondisplaceable distribution volume. Five subjects also underwent an additional scan to evaluate the within-day test-retest variability of 11C-AS2471907 volumes of distribution (V T). Results: 11C-AS2471907 time-activity curves were best fitted by the 2-tissue-compartment (2TC) model. 11C-AS2471907 exhibited a regionally varying pattern of uptake throughout the brain. The V T of 11C-AS2471907 ranged from 3.7 ± 1.5 mL/cm3 in the caudate nucleus to 14.5 ± 5.3 mL/cm3 in the occipital cortex, with intermediate values in the amygdala, white matter, cingulum, insula, frontal cortex, putamen, temporal and parietal cortices, cerebellum, and thalamus (from lowest to highest V T). From the blocking scans, nondisplaceable distribution volume was determined to be 0.16 ± 0.04 mL/cm3 for 11C-AS2471907. Thus, nearly all uptake was specific and the binding potential ranged from 22 in the caudate to 90 in the occipital cortex. Test-retest variability of 2TC V T values was less than 10% in most large cortical regions (14% in parietal cortex) and ranged from 14% (cerebellum) to 51% (amygdala) in other regions. The intraclass correlation coefficient of 2TC V T values ranged from 0.55 in the white matter to 0.98 in the cerebellum. Conclusion: 11C-AS2471907 has a high fraction of specific binding in vivo in humans and reasonable within-day reproducibility of binding parameters.

Inhibition of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) represents a potential mechanism for improving pain conditions. ASP3662 is a potent and selective inhibitor of 11β-HSD1. Two phase I clinical studies were conducted to assess the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of single and multiple ascending doses of ASP3662 in healthy young and elderly non-Japanese and young Japanese subjects. Nonlinear, more than dose-proportional PKs were observed for ASP3662 after single-dose administration, particularly at lower doses (≤ 6 mg); the PKs at steady state were dose proportional, although the time to ASP3662 steady state was dose dependent at lower doses (≤ 2 mg). Similar PKs were observed among young Japanese, young non-Japanese, and elderly non-Japanese subjects. Specific inhibition of 11β-HSD1 occurred after both single and multiple doses of ASP3662. A marked dissociation between PKs and PDs was observed after single but not multiple doses of ASP3662. ASP3662 was generally safe and well tolerated.

Limitations of a polythetic-categorical classification system has sparked ongoing quantitative efforts to establish a valid and reliable method for diagnosing mental illness. Dimensional methods of classification, such as the Hierarchical Taxonomy of Psychopathology (HiTOP), have been found to ameliorate the limitations of a categorical approach - despite the provisional placement of a Somatoform spectrum. The current investigation sought to elucidate the placement of the Somatoform spectrum within the HiTOP model, and to further corroborate discriminant and convergent validity of the Somatoform spectrum. Using a sample of patients seeking chronic low-back pain treatment (n = 200), superior model fit suggested Somatoform fits better as a separate spectrum from Internalizing and placing Somatoform as a subfactor of Internalizing did not improve model fit. Discriminant and convergent validity with an external criteria demonstrated distinctiveness of the Somatoform spectrum from the Internalizing spectrum in the HiTOP model.

Background Bariatric surgery usually results in substantial weight loss and a reduction in medical comorbidities. Many patients, as a consequence of the weight loss, subsequently evidence loose, redundant skin. Objectives This investigation seeks to examine the prevalence of body contouring surgery (BCS) by patients approximately 4 to 5 years after Roux-en-Y gastric bypass surgery. Demographics, change in BMI, and psychosocial variables were also used to predict body dissatisfaction, desire for BCS, and patients who reported obtaining BCS. Setting The clinical sites involved in the Longitudinal Assessment of Bariatric Surgery project, which included 10 hospitals across the United States. Methods The sample comprised 1159 patients who underwent Roux-en-Y gastric bypass and were enrolled in the Longitudinal Assessment of Bariatric Surgery-2 study. Participants were surveyed using the Excessive Skin Survey and other psychosocial measures at their 4- or 5-year postoperative outcome. The participants were predominately women (80.5%), Caucasian (88.3%), and middle-aged (mean = 46.1 yr, standard deviation = 11.11 yr). Results Participants reported modest degrees of being bothered by excessive skin, primarily in their waist/abdomen, thighs, and chest/breasts body areas. Only 11.2% of the sample had undergone any BCS procedure, and a majority of those participants paid "out of pocket" for BCS. Desire for BCS and body dissatisfaction 4 to 5 years postsurgery was associated with higher depression scores and poorer quality of life scores. Conclusions Excessive skin is associated with poorer psychosocial functioning. Despite reporting modest levels of being bothered by excessive skin and body dissatisfaction, only a small fraction of participants underwent BCS. Cost of BCS was reported to be a primary barrier for not obtaining BCS. All rights reserved.

Layer V pyramidal neurons constitute principle output neurons of the medial prefrontal cortex (mPFC)/neocortex to subcortical regions including the intralaminar/midline thalamic nuclei, amygdala, basal ganglia, brainstem nuclei and the spinal cord. The effects of 5-hydroxytryptamine (5-HT) on layer V pyramidal cells primarily reflect a range of excitatory influences through 5-HT

Psychopathology has been associated with patient reports of poor outcome and an algorithm has been useful in predicting short-term outcomes. The objective of this study is to investigate whether a pre-surgical psychological algorithm could predict 1-year spine surgery outcome reports, including pain, functional disability, and emotional functioning. A total of 1,099 patients consented to participate. All patients underwent spine surgery (e.g., spinal fusion, discectomy, etc.). Pre-operatively, patients completed self-report measures prior to surgery. An algorithm predicting patient prognosis based on data from the pre-surgical psychological evaluation was filled out by the provider for each patient prior to surgery. Post-operatively, patients completed self-report measures at 3- and 12-months after surgery. Longitudinal latent class growth analysis (LCGA) was used to derive patient outcome groups. These outcome groups were then compared to pre-surgical predictions made. LCGA analyses derived three groups of patients from the reported outcome data (entropy = .84): excellent outcomes, good outcomes, and poor outcomes. The excellent and good groups demonstrated improvements over time, but the poor outcome groups, on some measures, reported worsening of pain, functional disability, and emotional functioning over time. The pre-surgical algorithm yielded good concordance with the statistically derived outcome groups (Kendall's W = .81). Using a pre-surgical psychological evaluation algorithm for predicting long-term spine surgery outcomes can identify patients who are unlikely to report good outcomes, and point to areas for psychological intervention that can either improve surgery results or to be utilized as alternatives to elective spine surgery. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The Attitudes Toward Persons with Obesity (ATOP) scale is widely used to assess stigmatization toward persons with obesity. The measure has previously been suggested to assess three facets-self-esteem, personality, and social difficulties-however, psychometric support for this has been inconsistent and warrants further study if the measure intends to be scored this way.Explore and confirm the factor structure of the ATOP in people assessed prior to bariatric surgery and reassessed 1 year postoperatively SETTING: Midwestern hospital in the USA.Three-hundred sixteen people who were seeking bariatric surgery were assessed preoperatively, and 161 of those people were reassessed 1 year after surgery with a battery of measures including the ATOP. Exploratory factor analysis (EFA) was performed on ATOP data from a random split-half of people before surgery, and confirmatory factor analysis (CFA) was performed on the second randomly selected half. With the postoperative sample, a CFA was performed, testing the best-fitting model from the preoperative CFA findings.The EFA suggested a two-factor structure interpreted as self-esteem and personality/social difficulties. This structure was supported by CFA performed on the second randomly selected half of people at preoperative assessment and by CFA performed on people 1 year following surgery. Tests of measurement invariance suggested that the two-factor structure was similar at both time points.Only two factors for the ATOP were empirically supported in the current sample (self-esteem and personality/social difficulties), which is slightly different from the three factors that were originally proposed when the measure was developed. This factor structure is supported both prior to bariatric surgery and 1 year after bariatric surgery.