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BACKGROUNDKetamine may have antidepressant properties, but its acute psychoactive effects complicate successful masking in placebo-controlled trials.METHODSIn a triple-masked, randomized, placebo-controlled trial, 40 adult patients with major depressive disorder were randomized to a single infusion of ketamine (0.5 mg/kg) or placebo (saline) during anesthesia for routine surgery. The primary outcome was depression severity measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at 1, 2, and 3 days post-infusion. The secondary outcome was the proportion of participants with clinical response (≥50% reduction in MADRS scores) at 1, 2, and 3 days post-infusion. After all follow-up visits, participants were asked to guess which intervention they received.RESULTSMean MADRS scores did not differ between groups at screening or pre-infusion baseline. The mixed-effects model showed no evidence of effect of group assignment on post-infusion MADRS scores at 1 to 3 days post-infusion (-5.82, 95% CI -13.3 to 1.64, p=0.13). Clinical response rates were similar between groups (60% versus 50% on day 1) and comparable to previous studies of ketamine in depressed populations. Secondary and exploratory outcomes found no evidence of benefit for ketamine. 36.8% of participants guessed their treatment assignment correctly; both groups allocated their guesses in similar proportions.CONCLUSIONA single dose of intravenous ketamine compared to placebo has no short-term effect on the severity of depression symptoms in adults with major depressive disorder. This trial successfully masked treatment allocation in moderate-to-severely depressed patients using surgical anesthesia. While it is impractical to use surgical anesthesia for most placebo-controlled trials, future studies of novel antidepressants with acute psychoactive effects should make efforts to fully mask treatment assignment in order to minimize subject-expectancy bias. (ClinicalTrials.govnumber,NCT03861988)

Objectives The aim of this study was to compare Black and White mental health care patients’ perceptions of their providers’ and their own participation in patient-centered mental health care. Perceptions of patient-centered care (PCC) in relation to the Multidimensional Model of Racial Identity were explored. Methods Black and White veterans receiving mental health care (n = 82) completed surveys assessing patient activation, involvement in care, perceptions of PCC, and therapeutic alliance. Black participants (n = 40) also completed the Multidimensional Inventory of Black Identity. Results There were no differences by race in perceived PCC, though Black participants had lower levels of therapeutic alliance with their mental health care provider and were less activated. Black identity centrality, private regard, and public regard were positively related to PCC and elements of PCC such as patient information seeking/sharing. Conclusions Intragroup identity variables such as racial centrality, regard, and ideology influenced perceived PCC among Black participants. Race identity variables should be explored in future research on racial disparities and PCC. Practice implications Mental health care providers serving Black patients should create opportunities to discuss racial identity and race-related experiences as part of their efforts to improve therapeutic alliance and increase the patient-centeredness of care.

Purpose Our group previously reported the safety and feasibility of the off- pump HeartMate 3 left ventricular assist device in a small cohort of high-risk patients. We now present a larger cohort who underwent off-pump HeartMate 3 LVAD placement, the majority via a less invasive approach. The study's primary objective was the safety and feasibility of the off-pump technique compared to the standard on-pump approach with an emphasis on the less invasive technique. Methods We retrospectively reviewed all patients who underwent HeartMate 3 LVAD implantation at our institution since June of 2019. One hundred and sixty-one of these patients underwent on- pump implantation while 52 underwent off-pump implantation with 49 of them (94%) undergoing a less invasive approach which includes bilateral thoracotomies and thoracotomy with hemi- sternotomy. Results Preoperative characteristics were similar between groups. More patients in the off-pump group were categorized as INTERMACS Profile 1 at the time of implant (67% vs 29% in the on-pump group, p

Trauma is associated with debilitating acute and posttraumatic stress disorders, which have limited treatment options. We report on a patient undergoing surgical hand repair after a recent knife attack who experienced vivid dreaming and subsequent remission of acute stress disorder. After local anesthesia with propofol sedation she recalled a dream wherein she relived the attack, sought medical care, completed surgery, and returned home with a healed hand. While intraoperative dreaming is common, this case details potential associations between anesthetic state, dreaming, intraoperative electroencephalography, and remission of a psychiatric disorder. Our experience suggests a novel intervention for stress disorders.

Black-white disparities in mental healthcare persist, despite efforts to eliminate them via culturally competent care. To gain insight into how providers implement culturally competent care practices, interviews were conducted with mental healthcare providers' about their self-reported behaviors with black and white clients and their perceptions of how race affects the treatment they provide. Thematic analysis was used to analyze 12 semi-structured interviews with providers from a Veterans Affairs healthcare system. Three sets of themes emerged: providers' general beliefs and behaviors (discomfort discussing race; belief that socioeconomic differences explained disparities; and use of coded language for race groups), providers' clinical beliefs and behaviors (race-matching enhances care and recognition of intersecting cultural identities), and providers' professional beliefs and behaviors (participation in passive racism facilitated by provider-provider alliance). Mental healthcare providers showed good awareness of intersectionality and subtle racism but held limiting beliefs that led to avoidance of discussions of race.

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10 −9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10 −9). Cannabis use disorder and cannabis use were genetically correlated (r g 0·50, p=1·50 × 10 −21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

Peer specialists, or individuals with lived experience of mental health conditions who support the mental health recovery of others, often work side-by-side with traditional providers (non-peers) in the delivery of treatment groups. The present study aimed to examine group participant and peer provider experiences with peer and non-peer group co-facilitation. Data from a randomized controlled trial of Living Well, a peer and non-peer co-facilitated intervention for medical illness management for adults with serious mental illness, were utilized. A subset of Living Well participants (n = 16) and all peer facilitators (n = 3) completed qualitative interviews. Transcripts were coded and analyzed using a general inductive approach and thematic analysis. The complementary perspectives of the facilitators, teamwork between them, skillful group pacing, and peer facilitator self-disclosure contributed to a warm, respectful, and interactive group atmosphere, which created an environment conducive to social learning. Guidelines for successful co-facilitation emerging from this work are described.

Insomnia is a prevalent experience for individuals with serious mental illness, and is one of the most common reasons for mental health referrals in the Veterans Health Administration. Insomnia also critically impacts psychiatric, cognitive and somatic outcomes. However, there is limited information about how people with serious mental illness (i.e. schizophrenia spectrum, bipolar, or major depressive disorders, with serious functional impairments) understand and respond to problems with their own sleep. Bringing this information to light will yield novel methods of research and treatment. The purpose of this study was to examine reactions to insomnia among veterans with serious mental illness and insomnia. An inductive phenomenological approach was used to collect data from 20 veterans with serious mental illness and insomnia using semi-structured interviews. Six themes were identified: Becoming Aware that Insomnia is a Problem; Response to and Dissatisfaction with Medications; Strategies to Get Better Sleep: Contrary to Usual Guidelines; Personal Responsibility for Getting Sleep; Resigned and Giving Up; and Acceptance and Persistence. These results provide insight into the process of identifying insomnia and the subsequent cognitive and behavioural responses that are used to manage sleep disturbances among veterans with serious mental illness, a group often excluded from gold-standard treatments for chronic insomnia. Clinical implications and recommendations for improving treatment efficacy are discussed.

Purpose While the feasibility of off-pump HeartMate 3 left ventricular assist device (LVAD) placement has already been demonstrated, the safety of this approach has not been reported to date. Methods We retrospectively reviewed all patients who underwent Heartmate 3 LVAD implantation and identified 19 off- pump patients. These were propensity-matched with 19 on-pump cases using the following variables: age, body mass index, INTERMACS profile, and surgical approach. The study's primary objective was the safety of the off-pump technique compared to the standard on-pump approach. Results Preoperative characteristics were similar between the groups (Table 1). Most patients presented with the highest acuity INTERMACS Profile 1 (92.1%). A higher frequency of off-pump patients was supported with extracorporeal membrane oxygenation prior to LVAD implantation (31.6 vs. 89.5%, p=0.001). Intraoperatively, a higher proportion of patients in the off-pump group required packed red blood cells administration (47.4% vs. 84.2%, p=0.038). In the immediate postoperative hours, off-pump patients showed trends toward lower vasoactive-inotropic requirements. Postoperative outcomes, including all of the major complications and short-term survival (Figure 1), were comparable between the groups. Conclusion Results from our retrospective propensity- matched analysis suggest that off-pump LVAD implantation can be offered as a safe alternative for high-risk LVAD candidates.

Ketamine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor that is both a drug of abuse and an FDA-approved anesthetic used off-label for treatment-resistant depression. Despite its growing clinical use for depression and pain, the relationships between the acute dissociative and affective effects of ketamine that contribute to its abuse liability and therapeutic potential, along with the neural mechanisms underlying these effects, are not well established. To address this need, we have implemented a randomized, double-blinded, placebo-controlled, within-subjects mechanistic trial. Healthy adult subjects undergo infusion with two fixed doses of subanesthetic racemic intravenous (IV) ketamine and placebo and their acute responses are assessed with self-report questionnaires, behavioral measures, hormone levels, and neuroimaging. As planned in our analysis strategy, we present interim results for the first 7 subjects of our study, focusing on dissociative and affective states and resting functional brain coupling signatures of these states. The first key finding was that ketamine induced dose-dependent increases in dissociation and related intoxication. Ketamine also altered affective states, reducing emotional insensitivity but increasing stress assessed by cortisol. Second, ketamine had an effect on altering brain connectivity, particularly for specific connections between regions of the reward and negative affect circuits and involving thalamic sub-regions. Third, regarding brain-response associations, ketamine-induced increases in amygdala-anteroventral thalamus coupling were correlated with greater dissociation and intoxication, whereas decreases in the coupling of the anteromedial thalamus and posterior parietal thalamus were correlated with increased sensory aspects of reward responsiveness. Additional specific correlations were observed between affective measures relevant to reward responsiveness or its absence and drug-altered changes in localized functional connections involving the nucleus accumbens (NAcc), amygdala, and thalamic sub-regions. We also discovered a consistent profile of negative associations between ketamine altered connectivity involving the NAcc and specific thalamic sub-regions and effects of anxiety. Further, drug-altered increases in the coupling of the amygdala and anteroventral thalamus were associated with increases in cortisol, an indicator of biochemical stress. The findings highlight the utility of integrating self-reports, objective measures, and functional neuroimaging to disentangle the brain states underlying specific acute responses induced by ketamine. With the likely continued expansion of FDA indications for ketamine, understanding acute responses and underlying neural mechanisms is important for maximizing the therapeutic potential of ketamine while minimizing the risk of promoting misuse or abuse of this substance. Clinical Trial Registration ID #: NCT03475277

A significant number of individuals experience physical, cognitive, and mental health symptoms in the months after acute infection with SARS-CoV-2, the virus that causes COVID-19. This study assessed depressive and anxious symptoms, cognition, and brain structure and function in participants with symptomatic COVID-19 confirmed by PCR testing (n=100) approximately three months following infection, leveraging self-report questionnaires, objective neurocognitive testing, and structural and functional neuroimaging data. Preliminary results demonstrated that over 1/5 of our cohort endorsed clinically significant depressive and/or anxious symptoms, and >40% of participants had cognitive impairment on objective testing across multiple domains, consistent with ‘brain-fog’. While depression and one domain of quality of life (physical functioning) were significantly different between hospitalized and non-hospitalized participants, anxiety, cognitive impairment, and most domains of functioning were not, suggesting that the severity of SARS-CoV-2 infection does not necessarily relate to the severity of neuropsychiatric outcomes and impaired functioning in the months after infection. Furthermore, we found that the majority of participants in a subset of our cohort who completed structural and functional neuroimaging (n=15) had smaller olfactory bulbs and sulci in conjunction with anosmia. We also showed that this subset of participants had dysfunction in attention network functional connectivity and ventromedial prefrontal cortex seed-based functional connectivity. These functional imaging dysfunctions have been observed previously in depression and correlated with levels of inflammation. Our results support and extend previous findings in the literature concerning the neuropsychiatric sequelae associated with long COVID. Ongoing data collection and analyses within this cohort will allow for a more comprehensive understanding of the longitudinal relationships between neuropsychiatric symptoms, neurocognitive performance, brain structure and function, and inflammatory and immune profiles.

Ein wichtiges Werkzeug zur praklinischen Bewaltigung eines Massenanfalls von Notfallpatienten ist der Einsatz eines Behandlungsplatzes (BHP). Unter bestimmten Umstanden ist der Aufbau am oder in der Nahe des Schadensortes jedoch nicht sinnvoll. Dies ist z. B. bei terroristischen Anschlagen der Fall. Fur die Krankenhauser ist das oberste Ziel bei einem Massenanfall von Patienten, die Behandlungskapazitat an den akut gestiegenen Bedarf anzupassen und die Funktionalitat des Krankenhauses zu erhalten. Durch den Aufbau eines BHP innerhalb eines Krankenhauses konnen diese Ziele moglicherweise erreicht werden. Ziele des vorgestellten Pilotprojekts waren die Erarbeitung und Einubung eines Konzepts zum Aufbau eines BHP innerhalb eines Klinikums der Maximalversorgung durch Einheiten des Katastrophenschutzes. Nach Bildung eines multiprofessionellen Expertengremiums wurden verschiedene Ortlichkeiten des Klinikums unter einsatztaktischen und raumlichen Gesichtspunkten evaluiert. Im Rahmen einer Anfahrts- und Aufbauubung wurden vordefinierte Fragestellungen im Hinblick auf Raumordnung, Fahrzeugkoordination, Kommunikation, Fuhrung und Patientenfluss durch Einsatzkrafte und Evaluatoren bewertet und Losungen konsentiert. Der Aufbau und Betrieb eines Behandlungsplatzes innerhalb des Klinikums waren problemlos moglich. Durch den konsequenten Einsatz von Einsatzabschnittsleitern gestalteten sich die Fahrzeugkoordination und der simulierte Patientenfluss reibungslos. Die Fuhrung des BHP durch eine Sanitatseinsatzleitung (organisatorischer Leiter und leitender Notarzt) in enger Abstimmung mit der Krankenhauseinsatzleitung hat sich als sinnvolles Konzept dargestellt. Die anfanglichen Kommunikationsprobleme zwischen Sanitatseinsatzleitung und Krankenhauseinsatzleitung konnten durch Austausch von schnurlosen Telefonen und die Errichtung eines Digitalfunk-Repeaters behoben werden. Bei „Ad-hoc-Lagen“ sind Konzepte zu favorisieren, welche auf den laufenden Betrieb des „Alltagsgeschafts“ setzen, der bedarfsgerecht sukzessiv personell und materiell erweitert wird. Bei Gefahren- oder Schadenslagen mit ausreichender Vorlaufzeit (>60 min) ist darauf zu achten, die Funktionalitat des Krankenhauses so wenig wie moglich zu beeintrachtigen. Der Einsatz eines Behandlungsplatzes innerhalb einer Klinik (BHPK) konnte ein mogliches Konzept hierfur sein. Weitere Ubungen sind notwendig, um BHPK unter realen Bedingungen mit Patientenstromen und Personaleinsatz weiterzuentwickeln.

Soil symbiotic microorganisms promote recruitment of legume forage species in grassland ecosystems by enhancing provision for nutrients. We studied the effects of arbuscular mycorrhizal fungi (AMF) on plant growth, mineral nutrition and biological nitrogen fixation of Melilotus alba Med., a forage legume with potential use in subtropical grasslands. Responses to AMF inoculation (a mix of Funneliformis mosseae, Rhizophagus irregularis and Simiglomus hoi) and phosphate fertilization were evaluated in plants growing for 12 weeks in a subtropical soil. All plants were previously inoculated with a suspension of Rhizobium meliloti. Plant responses were assessed in terms of mycorrhizal colonization, biomass production, mineral nutrition (P and N) and proportion of biological nitrogen fixation by 15N natural abundance method. The results showed that when soil phosphorus availability was very low, regardless of the degree of AMF colonization, the generation of mycorrhizae did not reach a significant impact on plant nutrition and biomass production. But under a relatively higher phosphorus provision, AMF symbiosis showed positive effects on phosphorus accumulation, nitrogen nutrition and biomass production, linked to an enhancement of biological nitrogen fixation. The results strengthen our understanding of how synergistic effects between belowground symbionts (in this case AMF + Rhizobium) could promote the recruitment of forage legumes in subtropical grassland soils.

We compare African-American and White clients receiving services at 13 rural and semi-rural community mental health agencies (CMHAs) and the impact of Medicaid on the use of crisis and outpatient services. SEM was utilized to model the indirect effect of crisis services between the association of Medicaid and total hours of outpatient services. We modeled the moderating effects of race using mixture modeling and latent class. The base model showed a non-significant indirect effect between having Medicaid and total hours of services through the use of crisis services (Indirect effect = 0.01, p = .98). African-American clients who received Medicaid were more likely to use crisis services ([Formula: see text], which was associated with increased hours of outpatient services ([Formula: see text]. In general, Medicaid was not related to increase service or crisis service usage. However, African-American clients access crisis services significantly more than White clients.

17β-estradiol (E2) levels in women correlate with multiple neuropsychiatric symptoms, including those that are stress-related. Furthermore, prior work from our group has demonstrated that E2 status influences DNA methylation (DNAm) across the genome. We developed and validated a DNAm-based predictor of E2 (one of four naturally occurring estrogens) using a training set of 183 females and a test set of 79 females from the same traumatized cohort. We showed that predicted E2 levels were highly correlated with measured E2 concentrations in our testing set (r ​= ​0.75, p ​= ​1.8e-15). We further demonstrated that predicted E2 concentrations, in combination with measured values, negatively correlated with current post-traumatic stress disorder (PTSD) (β ​= ​−0.38, p ​= ​0.01) and major depressive disorder (MDD) diagnoses (β ​= ​−0.45, p ​= ​0.02), as well as a continuous measure of PTSD symptom severity (β ​= ​−2.3, p ​= ​0.007) in females. Finally, we tested our predictor in an independent data set (n ​= ​85) also comprised of recently traumatized female subjects to determine if the predictor would generalize to a different population than the one on which it was developed. We found that the correlation between predicted and actual E2 concentrations in the external validation data set was also high (r ​= ​0.48, p ​= ​3.0e-6). While further validation is warranted, a DNAm predictor of E2 concentrations will advance our understanding of hormone-epigenetic interactions. Furthermore, such a DNAm predictor may serve as an epigenetic proxy for E2 concentrations and thus provide an important biomarker to better evaluate the contribution of E2 to current and potentially future psychiatric symptoms in samples for which E2 is not measured.

Precision psychiatry is an emerging integrative approach that unifies the scientific foundation of the discipline and recent technological advances, directing them at narrowing the gap between discovery and clinical translation. Although depression in particular exerts a staggering toll, an understanding of which disease processes underlie the heterogeneity of depression as it is experienced by each person is lacking. While many effective treatments are available for depression, finding the right treatment for the right patient at the right time remains largely a matter of trial-and-error. Furthermore, the DSM provides a system for clinicians and researchers to communicate reliably about observed diagnostic signs and symptoms, yet a taxonomy does not exist for diagnosis and for guiding treatment choices that is based in an understanding of underlying pathophysiology. Thus, there is an urgent clinical need for an innovative approach. Functional imaging of large-scale neural circuits is one approach to developing a mechanistic taxonomy. Retrospective studies show that understanding disruptions to brain circuits markedly improves our ability to determine which patients are likely to benefit from which interventions. In this chapter, the authors present a model for precision psychiatry and why it is urgently needed at this time. Their primary focus is on the organ of dysfunction in psychiatry—the brain. They complement this approach with consideration of two blood-based markers, including inflammatory markers and pharmacogenetics. They review emerging findings that form the foundations of precise classification and initial results for precise treatment planning using these tools. They conclude by highlighting necessary steps to accelerate precision psychiatry from vision to reality.

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder (MDD). Total sample sizes per phenotype ranged from ~2,400 to ~537,000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg=0.18; false discovery rate q=0.0006), cannabis initiation and AN (rg=0.23; qwith binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating (rgs=-0.19 to −0.23; qs

Background Although repetitive transcranial magnetic stimulation (‘TMS’) is becoming a gold standard treatment for pharmacoresistant depression, we lack neural target biomarkers for identifying who is most likely to respond to TMS and why. To address this gap in knowledge we evaluate neural targets defined by activation and functional connectivity of the dorsolateral prefrontal cortex-anchored cognitive control circuit, regions of the default mode network and attention circuit, and interactions with the subgenual anterior cingulate. We evaluate whether these targets and interactions between them change in a dose-dependent manner, whether changes in these neural targets correspond to changes in cognitive behavioral performance, and whether baseline and early change in neural target and cognitive behavioral performance predict subsequent symptom severity, suicidality, and quality of life outcomes. This study is designed as a pragmatic, mechanistic trial partnering with the National Clinical TMS Program of the Veteran’s Health Administration. Methods Target enrollment consists of 100 veterans with pharmacoresistant Major Depressive Disorder (MDD). All veterans will receive a clinical course of TMS and will be assessed at ‘baseline’ pre-TMS commencement, ‘first week’ after initiation of TMS (targeting five sessions) and ‘post-treatment’ at the completion of TMS (targeting 30 sessions). Veterans will be assessed using functional magnetic resonance imaging (fMRI), a cognitive behavioral performance battery, and established questionnaires. Multivariate linear mixed models will be used to assess whether neural targets change with TMS as a function of dose (Aim 1), whether extent and change of neural target relates to and predicts extent of behavioral performance (Aim 3), and whether extent of neural target change predicts improvement in symptom severity, suicidality, and quality of life (Aim 3). For all three aims, we will also assess the contribution of baseline moderators such as biological sex and age. Discussion To our knowledge, our study will be the first pragmatic, mechanistic observational trial to use fMRI imaging and cognitive-behavioral performance as biomarkers of TMS treatment response in pharmacoresistant MDD. The results of this trial will allow providers to select suitable candidates for TMS treatment and better predict treatment response by assessing circuit connectivity and cognitive-behavioral performance at baseline and during early treatment. Trial registration ClinicalTrials.gov NCT04663481, December 5th, 2020, retrospectively registered. The first veteran was enrolled October 30th, 2020.

One prominent social-cognitive model of internalized stigma by Corrigan and his colleagues (2012; 2002) proposes that individuals are exposed to societal stereotypes about mental illness, at least tacitly agree with them, and may apply them to oneself, engendering harmful self-beliefs. There is limited empirical support for this model in serious mental illness. Moreover, it is not clearly established how internalized stigma and its associated factors impact recovery in this population. The current study uses structural equation modeling (SEM) to assess the social-cognitive model's goodness of fit in a sample of Veterans with serious mental illness (Veteran sample, n = 248), and then validates the model in a second and independent sample of individuals receiving community-based psychiatric rehabilitation services (community sample, n = 267). Participants completed the Self-Stigma of Mental Illness Scale (SSMIS; Corrigan et al., 2006) and measures of self-esteem, self-efficacy, and recovery attitudes. Consistent with Corrigan and colleagues' formulation of internalized stigma, SEM analyses showed a significant indirect pathway from stereotype awareness, to stereotype agreement, to application to self, to self-esteem decrement, to poorer recovery attitudes. Additionally, there was a significant direct effect from stereotype awareness to self-esteem. This study shows that individuals with serious mental illness experience psychological harm from stigma in two ways: (1) through perceived public prejudice and bias, and (2) through internalizing these negative messages. In particular, stigma harms individuals' self-esteem, which then reduces their recovery attitudes.

After surgery or traumatic injury, corneal wound healing can cause a scarring response that stiffens the tissue and impairs ocular function. This fibrosis is caused in part by the activation of corneal keratocytes from a native mechanically quiescent state to an activated myofibroblastic state. This transformation is tied to signaling downstream of transforming growth factor-β1 (TGF-β1). Here, to better understand how biochemical and biophysical cues interact to regulate keratocyte activation and contractility, we cultured primary rabbit corneal keratocytes on flexible substrata of varying stiffness in the presence (or absence) of TGF-β1. Time-lapse fluorescence microscopy was used to assess changes in keratocyte morphology, as well as to quantify the dynamic traction stresses exerted by cells under different experimental conditions. In other experiments, keratocytes were fixed after 5 days of culture and stained for markers of both contractility and myofibroblastic activation. Treatment with TGF-β1 elicited distinct phenotypes on substrata of different stiffnesses. Cells on soft (1 kPa) gels formed fewer stress fibers and retained a more dendritic morphology, indicative of a quiescent keratocyte phenotype. Keratocytes cultured on stiff (10 kPa) gels or collagen-coated glass coverslips, however, had broad morphologies, formed abundant stress fibers, exhibited greater levels of α-smooth muscle actin (α-SMA) expression, and exerted larger traction forces. Confocal images of phospho-myosin light chain (pMLC) immunofluorescence, moreover, revealed stiffness-dependent differences in the subcellular distribution of actomyosin contractility, with pMLC localized at the tips of thin cellular processes in mechanically quiescent cells. Importantly, keratocytes cultured in the absence of TGF-β1 showed no stiffness-dependent differences in α-SMA immunofluorescence, suggesting that a stiff microenvironment alone is insufficient to induce myofibroblastic activation. Taken together, these data suggest that changes in ECM stiffness can modulate the morphology, cytoskeletal organization, and subcellular pattern of force generation in corneal keratocytes treated with TGF-β1.

Informed by the Network-Episode Model, 26 African-American men with serious mental illness and 26 members of their kinship networks completed in-depth qualitative interviews about their exp...

OBJECTIVE: Many adults with serious mental illness exhibit significant medical illness burden and poor illness self-management. The present study examined Living Well, a group-based illness self-management intervention for adults with serious mental illness, co-facilitated by two providers, one who has lived experience with co-occurring mental health and medical conditions. METHODS: Adults with serious mental illness (N=242) were randomized to Living Well or an active control. Participants completed assessments of quality of life, health attitudes, self-management behaviors, and symptoms at baseline, post-treatment, and follow-up. Emergency room use was assessed via chart review. Mixed effects models examined group by time interactions on outcomes. RESULTS: In Living Well, compared to the control, there were greater improvements at post-treatment in mental health related quality of life (t=2.15, df=619, p=.032), self-management self-efficacy (t=4.10, df=622, p

There is a critical need to better understand the neural basis of antidepressant medication (ADM) response with respect to both symptom alleviation and quality of life (QoL) in major depressive disorder (MDD). Reward neurocircuitry has been implicated in QoL, the neural basis of MDD, and the mechanisms of ADM response. Yet, we do not know whether change in reward neurocircuitry as a function of ADM is associated with change in symptoms and QoL. To address this gap in knowledge, we analyzed data from 128 patients with MDD who participated in the iSPOT-D trial and were assessed with functional neuroimaging pre- and post-ADM treatment (randomized to sertraline, venlafaxine-XR, or escitalopram). 58 matched healthy controls were scanned at the same time points. We quantified functional connectivity (FC) of reward neurocircuitry using nucleus accumbens (NAc) seed regions of interest, and then characterized how changes in FC relate to symptom response (primary outcome) and QoL response (secondary outcome). Symptom responders showed an increase in NAc-dorsal anterior cingulate cortex (ACC) FC relative to non-responders (p

Parkinson disease (PD) is a debilitating neurological condition that includes both motor symptoms and nonmotor symptoms (NMS). Psychiatric complaints comprise NMS and are collectively referred to as neuropsychiatric manifestations. Common findings include atypical depressive symptoms, anxiety, psychosis, impulse control disorder, deterioration of cognition, and sleep disturbances. Quality of life (QoL) of patients suffering from NMS is greatly impacted and many times can be more debilitating than motor symptoms of PD. We expand on knowledge gained from treatment models within a comprehensive care model that incorporates multidisciplinary specialists working alongside psychiatrists to treat PD. Insight into background, clinical presentations, and treatment options for patients suffering from neuropsychiatric manifestations of PD are discussed. Identifying symptoms early can help improve QoL, provide early symptom relief, and can assist tailoring treatment plans that limit neuropsychiatric manifestations.

El objetivo del presente trabajo fue establecer la condición de un pastizal del este de la provincia del Chaco. El trabajo se realizó en un establecimiento ganadero ubicado en la Localidad de Makallé. Se caracteriza por la presencia de un estrato herbáceo con predominio de gramíneas, de ciclo de crecimiento primavero-estival. Se determinó la proporción de especies clasificadas como preferidas, intermedias y/o indeseables, según sus características forrajeras; la cantidad de plantas anuales o malezas; la proporción de suelo desnudo; el vigor de las mejores especies y la producción estacional de materia seca. Teniendo en cuenta que el pastizal evaluado está integrado por un 40,4% de forrajeras preferidas que tuvieron un vigor alto; la cantidad de malezas fue baja (2%) al igual que la proporción de suelo desnudo sin cobertura vegetal (2%) y la producción forrajera fue de 1.639,1 kg/ha (promedio estacional). Se puede inferir en que la condición del pastizal es buena a excelente. No hay indicios en la vegetación y la producción del pastizal que manifiesten el comienzo de su deterioro.

Laurita M. (Laurie) Hack, DPT, PhD, MBA, FAPTA, has contributed to the physical therapy profession as an educator, researcher, and academic leader (Fig. 1). Dr Hack is Professor Emeritus in the Department of Physical Therapy at Temple University in Philadelphia, Pennsylvania. An independent consultant in physical therapy research and education, she also serves on the adjunct faculty in the Department of Physical Therapy at Arcadia University, Glenside, Pennsylvania. Dr Hack holds a BA from Wilmington College; an MS as the first professional degree in physical therapy from Case Western Reserve University; an MBA from the Wharton School, University of Pennsylvania; a PhD in higher education administration from the University of Pennsylvania; and a DPT from the MGH Institute of Health Professions. Dr Hack has clinical experience in outpatient, nursing home, and home care practice, especially in geriatrics, and has taught in the areas of practice management, geriatrics, clinical decision making, evidence-based practice, ethics, and health care systems. Her research interests include development of clinical expertise, the physical therapy workforce, and physical therapy education. She is a coauthor of Expertise in Physical Therapy Practice and of Evidence Into Practice. She is a coinvestigator in the grant, Physical Therapist Education for the Twenty First Century (PTE-21): Innovation and Excellence in Physical Therapist Education. Dr Hack has served the American Physical Therapy Association (APTA) as president of the Home, Health Section, the Health Policy & Administration Section, and the Education Section (now the Academy of Physical Therapy Education) and the Education Section (now the Academy of Physical Therapy Education), and as vice speaker and secretary of the APTA Board of Directors. Her APTA honors include being named a Catherine Worthingham Fellow of APTA, the Lucy Blair Service Award, and the Baethke-Carlin Award for Teaching Excellence.

Background In 2015, the American Council for Academic Physical Therapy (ACAPT) developed 3 strategic initiative panels to address integrated clinical education, student readiness, and common terminology for physical therapist clinical education. Objective The purpose of this paper is to describe the results of the work from the Common Terminology Panel. Design This was a descriptive, consensus-based study. Methods Using a consensus process and data that were collected from a review of literature, a document analysis of core and historical professional documents, focus group discussions, and an online open comment period, panel members developed a glossary for physical therapist clinical education. Results The final glossary included 34 terms in 4 categories. The categories included clinical education infrastructure, sites, stakeholders, and assessment. The ACAPT Board of Directors approved the glossary in June 2017, and the ACAPT membership approved the glossary in October 2017. Limitations The focus of the glossary was on physical therapist clinical education. A future, similar project should be undertaken for physical therapist assistant clinical education. Conclusion This process resulted in a comprehensive glossary for physical therapist clinical education; changes to several current terms, including “internship” and “full-time clinical education experience”; and the addition of new terms, including “preceptor” and “site coordinator for clinical education.” New terminology will provide standard language for consistent communication and a common framework for all stakeholders.

Experimental approaches to studying the consequences of pesticide use, including impacts on beneficial insects, are vital; however, they can be limited in scale and realism. We show that an ecoinformatics approach that leverages existing data on pesticides, pests, and beneficials across multiple fields can provide complementary insights. We do this using a multi-year dataset (2002-2013) on pesticide applications and density estimates of two pests, citrus thrips (Scirtothrips citri (Moulton [Thysanoptera: Thripidae])) and citrus red mites (Panonychus citri McGregor [Acari: Tetranychidae]), and a natural enemy (Euseius spp. predatory mites) collected from citrus groves in the San Joaquin Valley of California. Using correlative analyses, we investigated the long-term consequences of pesticide use on S. citri and P. citri population densities to evaluate the hypothesis that the pest status of these species is largely due to the disruption of natural biological control-i.e., these are induced pests. We also evaluated short-term pesticide efficacy (suppression of citrus thrips and citrus red mite populations immediately post-application) and asked if it was correlated with the suppression of Euseius predator populations. Although the short-term efficacy of different pesticides varied significantly, our dataset does not suggest that the use of citrus pesticides suppressed Euseius densities or worsened pest problems. We also find that there is no general trade-off between pesticide efficacy and pesticide risk to Eusieus, such that highly effective and minimally disruptive compounds were available to citrus growers during the studied time period.

Alcohol use disorder (AUD) is commonly encountered in clinical practice. A combination of psychosocial intervention and pharmacotherapy is the cornerstone of AUD treatment. Despite their efficacy, safety and cost-effectiveness, clinicians are reluctant to prescribe medications to treat individuals with AUD. Given the high rate of relapse with psychosocial intervention alone, increasing patient access to this underutilized treatment has the potential to improve clinical outcome in this difficult-to-treat population. Herein, we provide practical pharmacotherapy strategies to improve treatment outcome for AUD. We review the efficacy and side effects of both on- and off-label agents with a particular focus on clinical applicability. Recommendations are supported by findings from randomized controlled trials (RCT) and meta-analyses selected to be representative, where possible, of current treatment guidelines. The goal of this paper is to help readers use pharmacotherapy with greater confidence when treating patients with AUD.

La actividad ganadera tiene gran trascendencia para la Provincia de Corrientes dado que ocupa el 93% del total de la superficie agropecuaria. Las pequeñas unidades productivas familiares utilizan los animales para la venta, como fuerza de trabajo, autoconsumo y para generar ingresos a través de la elaboración de quesos denominados criollos Teniendo en consideración los materiales forrajeros regionales de alta disponibilidad y capaces de aportar nutrientes a la dieta animal a bajo costo, se optó por la metodología de Productor Demostrador, con el objetivo de difundir la experiencia y activar el proceso de adopción de la técnica propuesta. La caña de azúcar tradicionalmente se corta, pica y se entrega diariamente al animal. Sin embargo, en grandes cantidades, esta técnica se convierte en un obstáculo para el uso porque requiere de mano de obra diaria para los cortes, molienda y transporte. La caña de azúcar mezclada con cal (óxido de Calcio) es un método de conservación, que en esta experiencia permitió almacenar el alimento durante 7 días. Se trabajó con un productor demostrador de la localidad de Santa Ana, Corrientes, cuya apreciación de la experiencia fue sumamente positiva. El mismo se mostró satisfecho ya que no solo incrementó la producción de leche diaria sino que también pudo organizar mejor el tiempo dedicado a la alimentación de los animales. Por ello, podrá enseñarles a sus pares esta técnica que ha podido validar, con lo que se espera la difusión y transferencia tenga mayor impacto.

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case–control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10–13) and African ancestries (rs2066702; P = 2.2 × 10–9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit–hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

Objective The study was designed to explore patterns of prescriber communication behaviors as they relate to consumer satisfaction among a serious mental illness sample. Methods Recordings from 175 antipsychotic medication-monitoring appointments between veterans with psychiatric disorders and their prescribers were coded using the Roter Interaction Analysis System (RIAS) for communication behavioral patterns. Results The frequency of prescriber communication behaviors (i.e., facilitation, rapport, procedural, psychosocial, biomedical, and total utterances) did not reliably predict consumer satisfaction. The ratio of prescriber to consumer utterances did predict consumer satisfaction. Conclusions Consistent with client-centered care theory, antipsychotic medication consumers were more satisfied with their encounters when their prescriber did not dominate the conversation. Practice implications Therefore, one potential recommendation from these findings could be for medication prescribers to spend more of their time listening to, rather than speaking with, their SMI consumers.

Background Current research has found that higher rates of person-centered care (PCC) are associated with greater treatment adherence and positive treatment outcomes. However, the instruments used to access PCC primarily collect data on provider behavior, rather than consumer participation in PCC, despite the necessary co-equal and collaborative nature of PCC interactions. Objectives The objective of the current study was to test the hypotheses that: (1) the Perceived Involvement in Care Scale (PICS) consumer information subscale and the consumer decision making subscale are not correlated with the PPPC subscales and, (2) consumer perceptions of person-centeredness and of consumer involvement in care are significant independent explanatory variables for the theoretically or quantitatively grounded outcomes of therapeutic alliance, treatment adherence, and mental health care system mistrust. Methods Cross-sectional survey data was collected from 82 mental health care consumers receiving services at two Veterans Health Administration (VHA) facilities. Participants completed surveys on perceptions of PCC, consumer involvement in care, therapeutic alliance, medication adherence, and mental health care system mistrust. Results Significant correlation between the consumer participation and PCC subscales was mixed. Higher levels of PCC were associated with greater therapeutic alliance, less suspicion of mental health care systems, less perception of lack of support from providers, and less beliefs about group disparities in care. Consumer involvement was only significantly related to suspicion of mental health care systems. Discussion and conclusions These findings may be a function of the locus of each outcome variable. When conducting PCC research investigators should consider how the outcomes they are examining inform the method through which they measure patient-centeredness.

Background The Carnegie Foundation for the Advancement of Teaching commissioned the Preparation for the Professions Program, a qualitative study of professional education in 5 professions: medicine, nursing, law, engineering, and clergy. These studies identified curricular structures, instructional practices, assessment approaches, and environmental characteristics that support the preparation of professionals and led to educational reforms. The physical therapy profession has not had any in-depth, national investigation of physical therapist education since the Catherine Worthingham studies conducted more than 50 years ago. Objectives This research was a Carnegie-type study, investigating elements of excellence and innovation in academic and clinical physical therapist education in the United States. Design Five physical therapist education researchers from across the United States used a qualitative multiple-case study design. Methods Six academic and 5 clinical programs were selected for the study. The academic institutions and clinical agencies studied were diverse in size, institutional setting, geography, and role in residency education. Qualitative case studies were generated from review of artifacts, field observations, and interviews (individual and focus group), and they provided the data for the study. Results A conceptual framework grounded in 3 major dimensions was generated, with 8 supporting elements: (1) culture of excellence (shared beliefs and values, leadership and vision, drive for excellence, and partnerships), (2) praxis of learning (signature pedagogy, practice-based learning, creating adaptive learners, and professional formation), and (3) organizational structures and resources. Conclusion Building on the work of the Carnegie Foundation's Preparation for the Professions Program, a conceptual model was developed, representing the dimensions and elements of excellence in physical therapist education that is centered on the foundational importance of a nexus of linked and highly valued aims of being learner centered and patient centered in all learning environments, both academic and clinical.

Black consumers with serious mental illness (SMI) face significant challenges in obtaining quality mental health care and are at risk for experiencing significant disparities in mental health care outcomes, including recovery from mental illness. Patient-provider interactions may partly contribute to this disparity. The purpose of the current study was to understand the effects of race, psychosis, and therapeutic alliance on mental health recovery orientation among Veterans with SMI. Participants were Veterans who had an SMI being treated at two Veteran Affairs outpatient mental health clinics by a psychiatrist or nurse practitioner. Participants completed the Behavior and Symptom Identification Scale (BASIS-24), Mental Health Recovery Measure, and patient-report Scale to Assess the Therapeutic Relationship (STAR-P) which includes three subscales: positive collaboration, positive clinician input, and non-supportive clinician input. Regression analyses were used to determine interactive effects of race, psychosis severity, and therapeutic alliance variables. The sample was 226 Veterans (50% black, 50% white). Black participants were slightly older (p < .05), had higher baseline psychosis (p < .05), higher mental health recovery (p < .05), and perceived less non-supportive clinician input (p < .01) than white participants. Regression analyses indicated a significant three-way interaction among race, psychosis, and positive collaboration (p < .01). Greater positive collaboration attenuated the negative effect of higher levels of psychosis on mental health recovery orientation for black participants. Conversely, for white participants, positive collaboration had little effect on the negative relationship between psychosis severity and mental health recovery orientation. Increased levels of psychosis may inhibit patients’ perceptions of their ability to recover from SMI. However, for black participants, positive collaboration with mental health providers may moderate the effects of psychotic symptomatology.

A ‘fast-fail’ clinical-trial approach for depression indicates that engaging κ-opioid-receptor antagonism improves reward-circuit dysfunction and anhedonia.

Integrated pest management (IPM) guidelines for horticulture are typically established from years of experimental research and experience for a crop species. Ecoinformatics methods can help to quickly adapt these guidelines following major changes in growing practices. Citrus production in California is facing several major challenges, one of which is a shift away from sweet oranges [Citrus sinensis (L.) Osbeck Sapindales: Rutaceae] toward mandarins (including mostly cultivars of C. reticulata Blanco and C. clementina hort. ex Tanaka). In the absence of IPM guidelines for mandarins, growers are relying on pest information developed from oranges. We mined a database of management records from commercial growers and consultants to determine densities for four arthropod pests: cottony cushion scale (Icerya purchasi Maskell Hemiptera: Monophlebidae), citricola scale (Coccus pseudomagnoliarum Kuwana Hemiptera: Coccidae), European earwig (Forficula auricularia Linnaeus Dermaptera: Forficulidae), citrus red mite (Panonychus citri McGregor Acari: Tetranychidae), and a natural enemy, predatory mites in the genus Euseius (Congdon Acarina: Phytoseiidae). Densities of cottony cushion scale were approximately 10–40 times higher in the two most commonly grown mandarin species than in sweet oranges, suggesting this pest is reaching outbreak levels more often on mandarins. Densities of the other pests and predatory mites did not differ significantly across citrus species. This is a first step toward establishing IPM guidelines for mandarins for these pests; more research is needed to determine how arthropod densities relate to crop performance in mandarins.

The flow of liquid-gas systems on surfaces of corrugated sheet packings was studied numerically and experimentally. In simulations the concept of “effective contact angles” was used to take surface microstructures into account. With this approach, resolving the microstructure geometries by the numerical grid can be avoided, which significantly reduces the numerical effort. Several combinations of liquid systems and surface structures were investigated under various liquid flow rates. Generally, the approach showed good capability to reproduce the different flow morphologies found in the experiments and to predict the flow behavior for different flow rates.