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Translational, transdisciplinary, and transformational research stands to become a paradigm-shifting mantra for research in health disparities. A windfall of research discoveries using these 3 approaches has increased our understanding of the health disparities in racial, ethnic, and low socioeconomic status groups. These distinct but related research spheres possess unique environments, which, when integrated, can lead to innovation in health disparities science. In this article, we review these approaches and propose integrating them to advance health disparities research through a change in philosophical position and an increased emphasis on community engagement. We argue that a balanced combination of these research approaches is needed to inform evidence-based practice, social action, and effective policy change to improve health in disparity communities. [ABSTRACT FROM AUTHOR]

HIV-related comorbidities in underrepresented minority populations are reframed to include the co-occurring problems of systemic and structural barriers, within the mentoring context as a buffer and as action-oriented. This framework is discussed to improve racial and ethnic minority diversity in the research workforce from the perspectives of HIV comorbidities and mentoring. An integrated and coordinated approach to HIV-related comorbidities and inequities may be helpful when combined with research on the social-structural contributions as drivers to diversify the research workforce. We emphasize how these key research issues (a) provide a platform for training and retraining a highly motivated, diverse workforce and (b) facilitate the empowerment of these trained individuals to conduct rigorous scientific research on social-structural factors to mitigate the effects of these comorbidities. We conclude that a diverse research workforce is necessary but insufficient for improving training-related outcomes or reducing comorbidity effects. Additional considerations are warranted that include systemic approaches and changes at the structural and institutional levels.

Latinos represent a critical resource of talent that could be cultivated to expand the HIV research workforce. However, their rapid growth, as the largest and fastest growing ethnic minority group in the US population, has yet to translate into a significant increase in Latino health academic researchers. Historically, strategies to build a diverse research workforce have grouped together individuals from underrepresented minority populations obscuring significance between and within group differences. This limits approaches that are responsive to the diversity of needs and experiences of emerging investigators from underrepresented groups. In this article, we discuss challenges associated with heterogeneity of Latinos and barriers that impede research independence/career success in the context of a review of Latino-investigator targeted mentorship approaches on the behavioral-social science of HIV infection. Mentorship workforce strategies could benefit from a personalized framework emphasizing individualized and tailored approaches to address the limitations and gaps in knowledge regarding Latino research development. This perspective encourages increased emphasis on organizational and structural processes to aid in overcoming institutional-level barriers that impede research and career development. Recommendations are proposed for features and components of effective mentorship programs that will lead to robust outcomes for strengthening the Latino research workforce in the HIV research field and elsewhere., Competing Interests: Competing Interests: None declared., (Copyright © 2020, Ethnicity & Disease, Inc.)

Purpose of Review: This article critically reviews the utility of "phenotypes" as behavioral descriptors in aging/HIV research that inform biological underpinnings and treatment development. We adopt a phenotypic redefinition of aging conceptualized within a broader context of HIV infection and of aging. Phenotypes are defined as dimensions of behavior, closely related to fundamental mechanisms, and, thus, may be more informative than chronological age. Primary emphasis in this review is given to comorbid aging and cognitive aging, though other phenotypes (i.e., disability, frailty, accelerated aging, successful aging) are also discussed in relation to comorbid aging and cognitive aging., Recent Findings: The main findings that emerged from this review are as follows: (1) the phenotypes, comorbid aging and cognitive aging, are distinct from each other, yet overlapping; (2) associative relationships are the rule in HIV for comorbid and cognitive aging phenotypes; and (3) HIV behavioral interventions for both comorbid aging and cognitive aging have been limited. Three paths for research progress are identified for phenotype-defined aging/HIV research (i.e., clinical and behavioral specification, biological mechanisms, intervention targets), and some important research questions are suggested within each of these research paths.

This paper reviews some background issues as a foundation to place the ensuing supplement papers of this special issue section in context. The articles in this special supplement issue deepen and expand our understanding of biomedical, neurocognitive, and psychosocial aspects involved in human immunodeficiency virus (HIV) of older women, primarily through the use of the Women's Interagency HIV Study (WIHS) prospective cohort study. As it relates to research on the intersection between HIV and aging in women, we discuss (i) epidemiology as introduction, (ii) the cohort study design featuring the WIHS, (iii) definitions, (iv) models, and (v) section articles.

Objectives: We developed and evaluated a novel National Institutes of Health-sponsored Research and Mentorship Program for African American and Hispanic medical students embedded within the international, multisite HIV Vaccine Trials Network, and explored its impact on scientific knowledge, acquired skills, and future career plans., Methods: Scholars conducted social, behavioral, clinical, or laboratory-based research projects with HIV Vaccine Trials Network investigators over 8 to 16 weeks (track 1) or 9 to 12 months (track 2). We conducted an in-depth, mixed-methods evaluation of the first 2 cohorts (2011-2013) to identify program strengths, areas for improvement, and influence on professional development., Results: A pre-post program assessment demonstrated increases in self-reported knowledge, professional skills, and interest in future HIV vaccine research. During in-depth interviews, scholars reported that a supportive, centrally administered program; available funding; and highly involved mentors and staff were keys to the program's early success., Conclusions: A multicomponent, mentored research experience that engages medical students from underrepresented communities and is organized within a clinical trials network may expand the pool of diverse public health scientists. Efforts to sustain scholar interest over time and track career trajectories are warranted.

Abstract A growing body of evidence highlights the importance of competent mentoring in academic research in the field of HIV, particularly for early stage investigators from diverse, underrepresented backgrounds. We describe the development and implementation of a 2-day intensive workshop to train mid-level and senior-level investigators conducting HIV-related clinical and translational research across multiple academic institutions on more effective mentoring, with an emphasis on techniques to foster mentees of diversity. The workshop was focused on training mentors in techniques designed to improve the effectiveness of the mentor-mentee relationship, and included didactic presentations, interactive discussions, and small-group problem-based learning activities. Mid-level or senior-level faculty involved or planning to be involved in significant mentorship activities related to HIV research were eligible. Surveys and formal actions plans allowed for workshop evaluation and laid the groundwork for subsequent workshops. Twenty-six faculty from 16 U.S.-based institutions participated, with good representation across discipline, gender, and race/ethnicity. The sessions were highly rated and discussions and evaluations revealed important barriers and facilitators to mentoring, challenges and solutions related to mentoring mentees from diverse backgrounds, and specific tools to enhance mentoring effectiveness. The Mentoring the Mentors training program for HIV researchers focusing on early career investigators of diversity was the first of its kind and was well attended, was rated highly, and provided guidance for improving the program in the future. This training program fills an important gap in the HIV researcher community and offers guidance for training mentors interested in diversity issues in settings outside of HIV.

This introductory article provides background and sets the stage for the mentoring programs described in this special supplement. The goal of these programs is to develop scientists from racial/ethnic groups underrepresented in the area of HIV/AIDS research on issues related to mental health. We describe recent epidemiological trends associated with HIV infection in diverse populations, the need for mentoring programs to study disparities, and the ongoing mentoring programs supported by the National Institutes of Health targeting investigators underrepresented in the workforce. We also provide a summary of the content of the articles to follow. We conclude with a comment on future needs and actions.

We examine the challenges and barriers to quality mentoring for new investigators from underrepresented racial/ethnic groups and propose solutions for establishing a robust pipeline of early-career scientists who are well equipped to conduct research on disparities in HIV and mental health. In addition, we review contributions to this special supplement on mentoring and advocate a multilevel strategy that targets funding agencies, academic and research institutions, mentors, and mentees to enhance the diversity of the nation's scientific workforce and ensure that the public health system benefits from innovations derived from the optimal use of existing human capital.

The reciprocal interactions between the neuroendocrine, immune, and autonomic nervous systems are complicated, yet worthy of examination. A body of literature suggests that psychological factors such as stress, or psychiatric conditions such as major depression, may influence the immune system thereby altering host susceptibility to viral, or other types of infection. Alternately, in an attempt to limit infection and replication, the anti-viral host response, via innate and acquired immunity and subsequent release of pro-inflammatory cytokines and additional anti-viral mediators, may affect mood, cognition emotion, and possibly precipitate a psychiatric disorder. In order to address what is known regarding neuroendocrine-immune interactions in the context of HIV infection, the Center for Mental Health Research on AIDS convened a panel of scientists from diverse areas of expertise. Their primary charge was to examine whether stress-induced activation of the neuroendocrine system affects the immune system in a manner that negatively influences HIV disease progression, and whether HIV infection influences the central nervous system and behavior. The ensuing report summarizes their deliberations as they discussed the current body of information and identified outstanding critical questions in the areas of research. The group consensus was that the biological mediators of psychological status can play an important role in mediating HIV disease progression, particularly in subgroups of vulnerable patients; furthermore, they identified candidate biological mediators and mechanisms of disease progression. The Workgroup outlined the inherent challenges and limitations of such research and provided recommendations as to the future directions of research utilizing human, animal, and in vitro models of HIV-1 infection and stress.

Considerable progress has been made in the study of neurobiological correlates of suicidal behavior. These studies have confirmed the link between reduced serotonergic function and serious suicidal acts. They have localized the changes to the ventral prefrontal cortex and suggested how genetics, childhood rearing, alcoholism, substance abuse, gender, age, and cholesterol intake can modulate suicide rates through effects on the serotonergic system. Future studies need to apply this knowledge in the development of in vivo brain imaging and molecular genetic probes for study of high-risk patients. Identification of high-risk groups is essential for the conduct of controlled treatment trials, which are presently almost entirely lacking in suicidal populations. Previous clinical trials of medications and psychotherapies have targeted axis I or axis II disorders but not the predisposition to suicidal acts. Controlled treatment in high-risk patients must be undertaken to identify interventions that can reduce the propensity for suicidal acts. Such interventions will supplement current treatment strategies that target the associated psychiatric illness and reduce the opportunities to attempt suicide in high-risk patients by hospitalization.

Objective: To review the evidence for qualitatively distinct subtypes of human aggression as they relate to childhood psychopathology., Method: Critical review of the pertinent literature., Results: In humans, as well as in animals, the term aggression encompasses a variety of behaviors that are heterogeneous for clinical phenomenology and neurobiological features. No simple extrapolation of animal subtypes to humans is possible, mainly because of the impact of complex cultural variables on behavior. On the whole, research into subtypes of human aggression has been rather limited. A significant part of it has been conducted in children. Clinical observation, experimental paradigms in the laboratory, and cluster/factor-analytic statistics have all been used in an attempt to subdivide aggression. A consistent dichotomy can be identified between an impulsive-reactive-hostile-affective subtype and a controlled-proactive-instrumental-predatory subtype. Although good internal consistency and partial descriptive validity have been shown, these constructs still need full external validation, especially regarding their predicting power of comorbidity, treatment response, and long-term prognosis., Conclusions: Our understanding and treatment of children and adolescents with aggressive behavior can benefit from research on subtypes of aggression. The differentiation between the impulsive-affective and controlled-predatory subtype as qualitatively different forms of aggressive behavior has emerged as the most promising construct. Specific therapeutic hypotheses could be tested in this context and contribute to a full validation of these concepts.

Objective: This article reviews, discusses, and elaborates considerations and recommendations summarized by the biological research working group at the May 1993 NIMH conference on ethical issues in mental health research on children and adolescents., Method: Notes from the conference were summarized and supplemented by a computer search of relevant literature. Drafts were circulated for comment to national and international experts, some of whom joined as coauthors., Results: Issues addressed include possible overprotection by policy makers and institutional review boards arising out of the recognition of children's special vulnerability without equal recognition of their need for research; the definition of minimal risk, which has often been equated with no risk in the case of children; assessment of the risk-benefit ratio; procedures for minimization of risk, such as improved technology, "piggybacking" onto clinical tests, and age-appropriate preparation; the difficulty of justifying risk for normal controls; age-graded consent; special considerations about neuroimaging; "coercive" inducement, both material and psychological; disposition of unexpected or unwanted knowledge about individuals, including the subject's right not to know and parent's right not to tell; and socioeconomic status and cultural/ethnic equity., Conclusions: The working group adopted a position of advocacy for children's right to research access while recognizing that this advocacy must be tempered by thoughtful protections for child and adolescent subjects.

An analogue task of instrumental and hostile aggression during a competitive game, modified to minimize overlap between aggressive responses, was evaluated in 8- to 14-year-old clinically referred boys (n = 33). Postgame interviews indicated that the hostile response, an aversive noise, was perceived by over 80% of subjects as hostile and not instrumental. In contrast, the instrumental response, blocking the opponent's game, was perceived about equally as having instrumental and hostile functions. The hostile aggressive response was uniquely correlated with continuous performance task impulsive commission errors (r = .51), which supported the theoretical relation of hostile aggression to poor impulse control. These results suggest that instrumental and hostile aggression can be distinguished and when precisely defined are distinct in theoretically important ways.

An analogue task of instrumental and hostile aggression during a competitive game was evaluated in a sample of clinically-referred 8- to 12-year-old aggressive boys. Similar to a prior task in a normative sample (Hoving, Wallace, & La Forme, 1979), both types of aggression increased during provocation as compared to baseline, indicating the success of the provocation manipulation, with moderate correlations between the two aggressive responses. The aggressive group with attention-deficit hyperactivity disorder (ADHD) and the aggressive group without ADHD each had higher rates of instrumental aggression than controls. Only the aggressive/ADHD group had higher rates of hostile aggression than controls. Parent Child Behavior Checklist ratings indicated a modest but significant unique relationship between instrumental aggression and delinquency. The high rate of both types of aggression in the aggressive/ADHD group suggests that comorbid ADHD and aggression may result in qualitative differences in aggressive behavior. The high rate of hostile aggression in the aggressive-ADHD group supports theoretical assumptions regarding the relationship of hostile aggression to poor impulse control.

Prolactin (PRL) and cortisol (CORT) responses to a single oral administration (1.0 mg/kg) of the indirect serotonin agonist dl-fenfluramine were assessed in unmedicated prepubertal and adolescent males with disruptive behavior disorders (DBD). Neuroendocrine responses were correlated with scores on aggression rating scales in prepubertal and adolescent DBD patients and compared with those of matched adolescent normal control subjects. Net dl-fenfluramine-induced PRL and CORT release was not correlated with aggression rating scores in prepubertal and adolescent DBD patients and did not differ significantly between adolescent DBD patients and normal control subjects. Although the present study does not demonstrate a serotonergic abnormality in aggression or DBD, this may be more a reflection of limitations of the neuroendocrine challenge test procedures or the methods used than evidence that serotonergic function in the central nervous system is normal in aggression.

We examined the intraindividual stability of plasma prolactin (PRL) and cortisol responses to D,L-fenfluramine challenges (1.0 mg/kg, p.o.), at a 1-week interval, in boys with disruptive behavior disorders. Two acute administrations of fenfluramine produced consistent and predictable effects on net prolactin responses (peak delta PRL, area under the curve delta PRL), but variable and unpredictable effects on net cortisol responses. The time course and magnitude of fenfluramine blood levels, not nor-fenfluramine, paralleled net PRL responses to fenfluramine. These data indicate that the PRL response to fenfluramine shows continuity within individuals over the course of 1 week, providing a reliable index to reflect the overall function of the serotonin system in the limbic-hypothalamus.

beta-Phenylethylamine (PEA) is an amphetamine-like compound that is postulated to be a possible endogenous psychotogen. We studied locomotor response to PEA in two inbred progenitor strains of mice (C57BL/6 By and BALB/c By), their reciprocal F1 hybrids (B6CF1 and CB6F1), and seven recombinant inbred strains (CXBD, CXBE, CXBG, CXBH, CXBI, CXGJ, and CXBK). Univariate and multivariate statistical analyses were done. Heritability of the response to PEA was 82%. The strain distribution pattern was suggestive of the inheritance of the trait through a single major gene locus.

Five rat strains (Long-Evans Hooded, Zivic Miller, Lewis, Buffalo and Fischer-344) were tested in a shuttlebox conditioned avoidance task and the differences in the performance levels among the strains were noted. In parallel experiments using naive rats, the acetylcholine concentrations in eight brain regions and the acetylcholine turnover rate in five brain regions were determined for these strains. Interstrain differences in these parameters were found but no correlation between avoidance performance and either of these measures was apparent in any brain region studied. In separate experiments, no differences were found in the hippocampal acetylcholine concentration or the turnover rate among good performing Hooded, poor performing Hooded or untested Hooded rats. Similarly, no differences in regional acetylcholine turnover rates were found between naive rats of the Iowa Reactive and Nonreactive strains. [3H]-QNB (quinuclidinyl benzilate) binding was studied in three brain regions in the five strains, but no large interstrain differences in binding characteristics were found. In contrast to interpretations of other workers based on less direct assay methods involving fewer strains, we conclude that no strong correlation exists between avoidance performance ability and basal levels of brain cholinergic activity.

The ability of beta-phenylethylamine (PEA) to reverse (1) chlorpromazine-induced activation of striatal tyrosine hydroxylase, and (2) catalepsy produced by chlorpromazine, was examined. PEA, in a dose of 75 mg/kg, caused approximately 50% reduction in the degree of tyrosine hydroxylase stimulation produced by 20 mg/kg chlorpromazine. After 150 mg/kg PEA, complete reversal of tyrosine hydroxylase activation and partial reversal of catalepsy was observed. In these experiments, PEA was found to be about 10 times less potent than amphetamine and 25 times less potent than apomorphine. Thus, the ability of PEA to reverse the neurochemical and behavioral effects of striatal dopamine blockade is similar to known dopamine agonists.

Acute parachlorophenylalanine (pCPA) pretreatment (150 mg/kg, i.p., 24 h beforehand) potentiated facilitatory effects of mescaline (39.6 mg/kg i.p.) on shuttlebox escape/avoidance in hooded rats, tested in two different situations: 1. during aquisition of avoidance behavior (Experiment 1); and 2. in stable pretrained poor avoiders (Experiment 2). pCPA alone did not influence avoidance behavior in either situation. Mescaline, with pCPA pretreatment, may be associated with long-term behavioral effects; all rats treated with this combination were later found to be poor avoiders, unable to achieve a stable baseline of good avoidance. pCPA significantly depleted brain norepinephrine and dopamine, as well as serotonin, measured after testing in the second situation.

Administration of the combination of antidepressant and neuroleptic drugs has been reported to have a synergistic effect in the treatment of delusional depression. The effects of chronic coadministration of imipramine (IMIP) and chlorpromazine (CPZ) on beta-adrenergic and alpha 2-adrenergic binding sites in rat cerebral cortex were studied. The combination caused the same reduction in the number of beta-adrenergic receptors as IMIP alone. No changes in alpha 2-adrenergic receptors were observed with IMIP and/or CPZ.

Binding characteristics of tritiated imipramine on blood platelets were determined in daytime hospitalized prepubertal children who had mixed diagnoses of conduct disorder (CD) plus attention deficit disorder hyperactivity (ADDH) and in inpatient adolescents who had a history of aggressive behavior. The number of (3H)-imipramine maximal binding sites (Bmax) was significantly lower in the prepubertal patient group of CD plus ADDH; the dissociation constant (Kd) was not significantly different. There were significant negative correlations between Bmax and the Externalizing or Aggressive factors of the Child Behavior Checklist when the CD plus ADDH prepubertal patients were combined with their matched controls and within the adolescent inpatient group. We propose that a decreased platelet imipramine binding Bmax value, as an index of disturbed presynaptic serotonergic activity, is not specific to depression and may be used as a biologic marker for the lack of behavioral constraint in heterogeneous. populations of psychiatric patients.

Because of the increasing demand for refined techniques to record drug-induced motoric changes, we designed and evaluated a computer monitoring system with continuous measurement of different parameters of rat motor activity. This system is particularly useful for chronic drug studies because it can characterize patterns of behavior and combines the residential and experimental environments, thus enabling automated behavioral measurement without experimenter intervention. Behavioral responses are detected by a capacitance-sensing device that generates bipolar analog voltages representing the location of the rat in its home cage. These voltages are first transduced, then amplified, and finally converted to digital signals in a computer that processes the input using algorithms to define specific responses. The technique pinpoints the exact location of the rat and identifies many kinds of responses simultaneously (e.g., rearing, circling) by tracking the path of movement or setting threshold limits. Some threshold values (representing rearing, gross movements, fine movements) were validated against stereotypy rating scales for amphetamine, apomorphine, and beta-phenylethylamine. Among these drugs, quantitatively distinct response profiles were obtained. The system has wide applications for studies of biological rhythms, sleep, aging, and drug toxicology.

Male healthy subjects, fasting 12 hours, ingested increasing amounts of a mixture containing a fixed proportion of seven essential amino acids (L-isoleucine 11.5%, L-leucine 18.0%, L-lysine 13.1%, L-methionine 18.0%, L-phenylalanine 18.0%, L-threonine 8.2%, L-valine 13.1%) and lacking tryptophan. The diets produced a rapid fall in plasma tryptophan which was proportional to the total amount of the amino acids ingested. Following the highest dose administered (36.6 g) plasma tryptophan fell to a minimum of about 35% the initial level and remained markedly reduced at 6 hours after treatment. The mechanism of this decrease and its potential clinical relevance are discussed.

N,N-Dimethyltryptamine (DMT) was given (ip) in different doses (0.25, 0.5, 1.0, 2.0, 4.0, 8.0 mg/kg) in a randomized order to a group of ten rats (Fisher 344/Mai) who were trained to a high, stable base line of conditioned avoidance responding in the shuttlebox. DMT produced dose-dependent disruptive effects, as a sigmoid function, with 1.0 mg/kg the minimal dose causing disruption and progressively more disruption with increasing doses, reaching a plateau at the highest dose. The disruptive effects were time-related, with onset and peak 8 min after injection, gradual decline thereafter, and disappearance by about 25-30 min. Both the threshold dose and time course for the disruptive effects correspond closely to what has been previously reported for DMT's psychological effects in humans.

Reliability and stability of neurological "subtle" ("soft") signs were assessed in 54 psychiatric patients and 25 normal children, aged 5-17 years, using the revised Neurological Examination for Subtle Signs (NESS). Acceptable interrater reliability (kappa greater than or equal to 0.50, or intraclass correlation coefficient greater than or equal to 0.70) was found for 40 of the 64 items tested. Test-retest reliability at 2 weeks was unsatisfactory for most of the categorically scored items, including some "classic" subtle signs such as overflows or dysrhythmias. Continuous items, such as time needed to perform 20 consecutive movements, remained mostly stable at retest. A practicing effect was evident only in the graphesthesia test. Overall internal consistency was good (Cronbach's alpha = 0.74). Given the poor stability of overflows and dysrhythmias, researchers and clinicians should rely more on subtle signs that can be assessed on continuous scales.