The influence of comorbid disorders on the episodicity of bipolar disorder in youth.

OBJECTIVE: Bipolar disorder (BP) frequently co-occurs with other psychiatric disorders. We examine whether course of anxiety disorders (ANX), attention deficit hyperactivity disorder (ADHD), disruptive behavior disorders (DBD), and substance use disorders (SUD) influence likelihood of recovery and recurrence of depression and mania in BP youth. METHOD: Weekly ratings of psychiatric disorder intensity were obtained from 413 participants of the Course and Outcome of BP Youth project, followed for an average of 7.75 years. Multiple-event Cox proportional hazards regression analyses examined worsening of comorbid disorders as predictors of mood episode recovery and recurrence. RESULTS: Increased severity in ANX and SUD predicted longer time to recovery and less time to next depressive episode, and less time to next manic episode. Multivariate models with ANX and SUD found that significant effects of ANX remained, but SUD only predicted longer time to depression recovery. Increased severity of ADHD and DBD predicted shorter time to recurrence for depressive and manic episodes. CONCLUSION: There are significant time-varying relationships between the course of comorbid disorders and episodicity of depression and mania in BP youth. Worsening of comorbid conditions may present as a precursor to mood episode recurrence or warn of mood episode protraction.

Examining the reliability of alcohol/drug use and HIV-risk behaviors using Timeline Follow-Back in a pilot sample.

Research on the course of substance use disorders (SUDs) faces challenges in assessing behavior over lengthy time periods. Calendar-based methods, like the Timeline Followback (TLFB), may overcome these challenges. This study assessed the reliability of self-reported weekly alcohol use, drug use, and HIV-risk behaviors over the past 90 days using an interview TLFB. Individuals with SUD in outpatient treatment (N = 26) completed the TLFB at baseline and then a week later with separate interviewers. Weekly ratings were aggregated across 4 week intervals for each administration. Intra-class correlations were used to compare agreement between the two administrations. Reliabilities for alcohol and drug use ratings ranged from good to excellent for most drug categories (ICCs = 0.76 - 1.00), except opioid use (other than heroin) and sedative use produced sub-standard reliabilities (ICCs = 0.29 - 0.74). HIV-risk behavior reliabilities also ranged from good to excellent (ICCs = 0.70 - 0.97), but were substandard for the number of casual sex partners for some intervals (ICCs = 0.29, 0.63). Findings extend support for the use of TLFB to produce reliable assessments of many drugs and HIV-risk behaviors across longitudinal intervals.

The Role of Socioeconomic Status in Patients With Cutaneous Melanoma of the Head and Neck.

OBJECTIVE: To determine the effects of socioeconomic status (SES) on cutaneous melanoma of the head and neck. DATA SOURCE: Surveillance Epidemiology and End Results (SEER) Program. REVIEW METHODS: We conducted a retrospective analysis of patients diagnosed with cutaneous melanoma of the head and neck from 2006 to 2018, utilizing population-based data including socioeconomic status (SES) assessed by the US-based Yost quintile index. SES quintiles ranged from Group 1 (lowest) to Group 5 (highest). We examined disease severity at diagnosis (stage, Breslow thickness, and spread) and survival outcomes (overall survival, cause-specific survival) to assess the impact of SES. RESULTS: A total of 53,967 melanomas of the head and neck were identified (14,146 females; 39,821 males; 51,890 white; 125 black; 317 other). Group 1 patients had a significantly higher percentage of end-stage disease (stage IV) at diagnosis (n = 101; 3.2% vs. n = 280; 1.9%, respectively) (p < .001), increased Breslow thickness (.80 mm vs .60 mm, respectively) (p < .001), and higher percentage of distant disease (n = 152; 3.6% vs. n = 431; 2.1%, respectively) (p < .001). Group 1 patients experienced a higher death rate from melanoma than group 5 patients (n = 585; 14% vs n = 1,753; 8.6%). Survival increased with SES. CONCLUSIONS: When evaluating cutaneous melanoma of the head and neck, low SES is related to more severe disease at diagnosis and worse survival outcomes. Addressing the underlying causes of this relationship could lead to more equitable management and survival outcomes. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

A 4-year prospective observational follow-up study of course and predictors of course in body dysmorphic disorder.

BACKGROUND: This report prospectively examines the 4-year course, and predictors of course, of body dysmorphic disorder (BDD), a common and often severe disorder. No prior studies have prospectively examined the course of BDD in individuals ascertained for BDD. Method The Longitudinal Interval Follow-Up Evaluation (LIFE) assessed weekly BDD symptoms and treatment received over 4 years for 166 broadly ascertained adults and adolescents with current BDD at intake. Kaplan-Meier life tables were constructed for time to remission and relapse. Full remission was defined as minimal or no BDD symptoms, and partial remission as less than full DSM-IV criteria, for at least 8 consecutive weeks. Full relapse and partial relapse were defined as meeting full BDD criteria for at least 2 consecutive weeks after attaining full or partial remission respectively. Cox proportional hazards regression examined predictors of remission and relapse. RESULTS: Over 4 years, the cumulative probability was 0.20 for full remission and 0.55 for full or partial remission from BDD. A lower likelihood of full or partial remission was predicted by more severe BDD symptoms at intake, longer lifetime duration of BDD, and being an adult. Among partially or fully remitted subjects, the cumulative probability was 0.42 for subsequent full relapse and 0.63 for subsequent full or partial relapse. More severe BDD at intake and earlier age at BDD onset predicted full or partial relapse. Eighty-eight percent of subjects received mental health treatment during the follow-up period. CONCLUSIONS: In this observational study, BDD tended to be chronic. Several intake variables predicted greater chronicity of BDD.

Oral treatment of rodents with fipronil for feed-through and systemic control of sand flies (Diptera: Psychodidae).

The sand fly Phlebotomus papatasi Scopoli is the vector of Leishmania major (Yakimoff & Schokhor), which is maintained in populations of burrowing rodents. The purpose of this study was to conduct a laboratory study to determine the efficacy of oral treatment of rodents with fipronil for control of sand flies that feed on rodent feces as larvae or on rodent blood as adults. We determined through larval bioassays that fipronil was eliminated in feces of orally-treated hamsters at a level that was significantly toxic to sand fly larvae for 21 d after the hamsters had been withdrawn from a fipronil-treated diet. Through bloodfeeding bioassays, we also found that fipronil was present in the peripheral blood of hamsters at a concentration that was significantly toxic to bloodfeeding adult female sand flies for 49 d after the hamsters had been withdrawn from their treated diet. The results of this study suggest that fipronil acts as well as or better than feed-through or systemic insecticides that previously have been measured against sand flies, and is particularly promising because this single compound acts against both larvae and bloodfeeding adults. An area-wide approach using rodent baits containing a fipronil could suppress vector populations that originate in the vicinity of rodent reservoirs, and could be used to eliminate the most epidemiologically important part of the vector population: female sand flies that take bloodmeals on rodent reservoirs.

Laboratory evaluation of rubidium as a long-lasting marker for bloodfeeding sand flies (Diptera: Psychodidae).

The objective of this study was to evaluate the use of the trace element rubidium (Rb) as a long-lasting systemic biomarker for bloodfeeding females of the sand fly Phlebotomus papatasi Scopoli. Baits containing Rb chloride were found to be palatable to hamsters in this study. We were able to detect Rb using a portable X-ray fluorescence analyzer in all sand flies that fed on Rb-treated hamsters for at least 14 d postbloodmeal. We also detected Rb in sand flies that took a bloodmeal from hamsters up to 10 d after the hamsters were withdrawn from a Rb-treated diet. Results of this study constitute proof of concept for the incorporation of Rb chloride into rodent baits for marking bloodfeeding sand flies, and suggest that Rb marking could be used as a technique for evaluating rodent-targeted sand fly control methods and in ecological studies on sand flies.

Evaluation of three feed-through insecticides using two rodent and two sand fly species as models.

The efficacy of 3 rodent feed-through insecticides (novaluron, pyriproxyfen, and ivermectin) was determined against larvae of the sand flies Phlebotomus duboscqi and P. papatasi using Syrian hamsters (Mesocricetus auratus) and Mongolian gerbils (Meriones unguiculatus) as laboratory models. For each insecticide, there were no significant differences between the longevity or percentage survival of sand fly larvae that had been fed feces of treated rodents for each sand fly or rodent species pairing. The results of this study suggest that larvae of P. duboscqi and P. papatasi are equally susceptible to the concentrations of the rodent feed-through insecticides tested in this study and that these insecticides are pharmacologically compatible with different rodent/sand fly interactions.

The Fc receptor on thymus-derived lymphocytes: II. Mitogen responsiveness of T lymphocytes bearing the Fc receptor.

The responsiveness of purified Fc- and Fc+ T lymphocytes, isolated from normal spleen cell populations by cell sorting on the fluorescence activated cell sorter, has been examined. Although both Fc- and Fc+ T cells responded to phytohemagglutinin, the response to concanavalin A (Con A) was found to be a characteristic of the Fc+ T lymphocyte. The poor responsiveness of the Fc- T cells to Con A was shown not to be due to a requirement of either different concentrations of Con A or for adherent cells. The addition of Fc+ T cells to the Fc- T cells in a ratio of 1:3 resulted in a mitotic response not significantly different from that observed with the purified Fc+ T cells alone and up to 15-fold greater than that of Fc- T cells alone. It is suggested that the Fc T cells can be recruited into mitosis as a result of Con A stimulation of the Fc+ T cells.

The Fc receptor on thymus-derived lymphocytes. I. Detection of a subpopulation of murine T lymphocytes bearing the Fc receptor.

Utilizing the fluorescence-activated cell sorter (FACS) and washed murine antibody-antigen complexes formed in antibody excess, we have demonstrated the presence of the Fc receptor on the surface of a distinct subpopulation of murine T lymphocytes. No differences in intensity of labeling with the complexes was observed when the Fc+ T lymphocytes were compared with Fc+ B lymphocytes. The majority of Fc+ T lymphocytes are small lymphocytes determined by light-scattering characteristics on the FACS. Separating Fc+ from Fc- T lymphocytes from spleens of mice primed 1 wk or 1 mo previously with keyhole limpet hemocyanin (KLH) revealed that the T cells capable of cooperating with DNP-KLH primed B cells to give an adoptive anti-DNP PFC response do not bear the Fc receptor.

Regulation of the immune system by synthetic polynucleotides. V. Effect on cell-associated immunoglobulin receptors and immunological memory.

Addition of polyadenylic-polyuridylic acid in complex form (poly A:U) without antigen to a suspension of spleen cells obtained from BALB/Aj mice primed 6 wk previously with human gamma-globulin (HGG) resulted in an immediate fourfold increase over background number of anti-HGG rosette-forming cells (RFC). Culture of similar cells in the presence of puromycin for 1-6 hr before poly A:U did not significantly reduce the response. Continued culture of primed spleen cells in the presence of poly A:U, resulted in a decrease of RFC to background levels within an hour followed by an increase again 6 hr later. This later increase in RFC was inhibited by addition of puromycin to the culture medium. The nonspecific stimulation by poly A:U of antibody production by primed spleen cells also was induced in vivo. Increases in splenic RFC were detectable 6 hr after intravenous injection of poly A:U alone, without antigen, into primed mice. The response peaked at 18 hr and had dissipated completely within 3 days. A second injection of poly A:U 24 hr or later after the first injection resulted in a second response, similar to the first with respect to kinetics and intensity. Rosette formation by poly A:U-stimulated cells could not be inhibited by mitotic poisons, but was inhibited by treatment of the cells with goat anti-mouse gamma-globulin serum, suggesting that the antibody involved was a 7S gamma-globulin. The decrease in RFC induced by culture of primed cells for 1 hr in poly A:U paralleled a decrease in secondary responsiveness of the cells to antigen. This poly A:U-induced inhibition of secondary responsiveness could be reversed by suspending the treated cells in supernatant fluids derived from poly A:U-stimulated cultures. The reversal was specific in that supernatant fluids removed from bovine serum albumin (BSA)-primed cells by poly A:U did not stimulate the response of HGG-primed cells to HGG. However supernatant fluids from BSA-primed cells caused the production of anti-HGG RFC if BSA rather than HGG was used as triggering antigen. The active factor in the supernatant fluids appeared to be a 7S gamma-globulin since activity was lost after 45 min incubation of the supernatant fluids in the presence of goat anti-mouse 7S gamma-globulin serum.

Studies on membrane-bound receptors for antigen. Preparation of populations of receptor-depleted lymphocytes.

THE EFFECT OF POLYADENYLIC: polyundylic acid complexes (poly A:U) on the amount of antibody on the surface of various populations of mouse lymphoid cells has been investigated by means of a sensitive measure of such activity-the binding by primed cell populations of beta-galactosidase (betaGZ) as an antigen. The sensitivity derives from the liberation of fluorescein from an artificial substrate, fluorescein-di-beta-galactopyranoside (FDbetaG). After incubation with 100 ng/ml of poly A:U, only 40% of the cells previously showing antigen-binding were still active. The optimum range of activity lay between 0.01-1.0 microg/ml poly A:U. Such cells showed increased RNA and protein synthesis as indicated by [(3)H]uridine and [(14)C]amino acid incorporation. The polynucleotide effect was abolished by incubation of the cells with sodium azide or iodoacetate, but not by puromycin. When the proteins on the cell surface were labeled by (125)I, poly A:U caused their release into the medium. Reports by others that the enhancing effect of polynucleotides on the immune response involves the adenylcyclase system are consistent with the finding reported here that reduction of binding by dibutryl 5'-cyclic monophosphoric acid (cAMP) and poly A:U were parallel in extent, and that theophylline and poly A:U acted synergistically in suboptimal concentrations of each.

The Fc receptor on thymus-derived lymphocytes. III. Mixed lymphocyte reactivity and cell-mediated lympholytic activity of Fc- and Fc+ T lymphocytes.

The involvement of Fc- and Fc+ T cells, separated on the fluorescence-activated cell sorter, in proliferative and cytotoxic responses to alloantigens was examined. The cytotoxic lymphocytes generated by in vivo exposure to allogeneic tumor cells were shown to express the Fc receptor. The proliferative responses to alloantigen exposure in mixed lymphocyte cultures was equivalent in intensity for unseparated T cells, the Fc+ T-cell fraction, and the Fc- T-cell fraction isolated from nonsensitized spleen cells. In contrast, the cytotoxic responses generated by the Fc- T-cell fraction (less than 1% Fc+) were much weaker than the cytotoxic responses generated by the Fc+ T-cell fraction (80-90% Fc+), and the responses of the Fc+ T-cell fraction were generally weaker than, or equal to the responses of unseparated T cells (Fc- T less than Fc+ T less than or equal to unseparated T). Mixtures of the Fc- and Fc+ T-cell fractions mounted stronger cytotoxic responses than the sum of the responses of either fraction alone. Examination of the Ly phenotypes of the synergizing populations revealed that the CL precursor activity (Ly-2+ T cells) resided in the Fc- T-cell population, and that the amplifier T-cell activity (Ly-1+ T cells) resided in the Fc+ T-cell population. The data are discussed in terms of T-cell heterogeneity, differentiation, and intercellular interaction.

The Fc receptor on thymus-derived lymphocytes. IV. Inhibition of binding of antigen-antibody complexes to Fc receptor-positive T cells by anti-Ia sera.

Treatment of splenic T lymphocytes with anti-Ia antiserum inhibits the binding of antigen-antibody (AgAb) complexes to the majority (less than 50%) of Fc receptor-positive (FcR+) T cells. A similar inhibition was observed with anti-H-2D and anti-H-2K sera but not with anti-Thy 1.2. Despite the presence of Ia determinants on peripheral T cells, as established by the inhibition of AgAb binding, Ia could not be detected on peripheral T cells by immunofluorescence assays. Data obtained with the AgAb-binding inhibition assay indicate that determinants controlled by loci mapping in the I-A and I-C, S, or G regions are present on the FcR+ T cells. Evidence is presented that subpopulations of T cells within the FcR+ T-cell population may be distinguishable on the basis of which I-region-controlled determinant is expressed. The data are discussed in terms of phenotypic and functional heterogeneity of T lymphocytes.

Indigenous perspectives on wellness and health in Canada: study protocol for a scoping review.

BACKGROUND: Indigenous communities are often portrayed from a deficit-based lens; however, Indigenous communities have self-determined perspectives of health and well-being that are strength based. The objective of this study will be to systematically map the literature on perspectives, concepts, and constructs of wellness and well-being in Indigenous communities in Canada. METHODS: A scoping review protocol was designed following the Arksey and O'Malley framework. We will search the following electronic databases (from inception onwards): MEDLINE, EMBASE, Web of Science, CINAHL, Academic Search Complete, Anthropology Plus, Bibliography of Native North Americans, Canadian Business and Current Affairs, and Circumpolar Health Bibliographic Database. Grey literature will be identified through searching dissertation databases, Google Scholar, and conference abstracts. We will include all types of literature in English, published and unpublished, including any study design, reviews and meta-analyses, dissertations, reports, and books. The literature considered should describe or reflect Indigenous perspectives that identify concepts or constructs related to well-being or wellness; literature can be from any setting in Canada. Two reviewers will independently screen all citations, full-text reports, and abstract data. Data analysis will involve quantitative descriptions (e.g. frequencies) and qualitative content analysis methods. DISCUSSION: This review will provide a synthesis of the literature on Indigenous perspectives, concepts, and constructs of wellness and well-being in Canada. We anticipate the study will contribute to improve our understanding of how Indigenous communities conceptualize and embody wellness. Our findings will provide a basis for engaging Indigenous stakeholders in future health research and informing future interpretations of how wellness is conceptualized, whether written or unwritten.

Personality traits as prospective predictors of suicide attempts.

OBJECTIVE: To examine higher order personality factors of negative affectivity (NA) and disinhibition (DIS), as well as lower order facets of impulsivity, as prospective predictors of suicide attempts in a predominantly personality disordered sample. METHOD: Data were analyzed from 701 participants of the Collaborative Longitudinal Personality Disorders Study with available follow-up data for up to 7 years. Cox proportional hazards regression analyses was used to examine NA and DIS, and facets of impulsivity (e.g. urgency, lack of perseverance, lack of premeditation and sensation seeking), as prospective predictors of suicide attempts. RESULTS: NA, DIS and all facets of impulsivity except for sensation seeking were significant in univariate analyses. In multivariate models which included sex, childhood sexual abuse, course of major depressive disorder and substance use disorders, only NA and lack of premeditation remained significant in predicting suicide attempts. DIS and the remaining impulsivity facets were not significant. CONCLUSION: NA emerged as a stronger and more robust predictor of suicide attempts than DIS and impulsivity, and warrants greater attention in suicide risk assessment. Distinguishing between facets of impulsivity is important for clinical risk assessment.

Juvenile-onset OCD: clinical features in children, adolescents and adults.

OBJECTIVE: To examine clinical correlates of juvenile-onset OCD across the lifespan. METHOD: Data collected at the intake interview from 257 consecutive participants with juvenile-onset OCD (20 children, 44 adolescents and 193 adults) in a naturalistic study of the clinical course of OCD were examined. Participants and parents of juvenile participants completed a structured diagnostic interview, rater-administered severity measures and self-report questionnaires. RESULTS: Children and adolescents (i.e. juveniles) shared similar features with the exception of age at onset and OCD symptom expression. Clinically meaningful differences between juvenile and adult participants were also found. Compared with adults, juveniles were more likely to be male, recall an earlier age at OCD onset and have different lifetime comorbidity patterns. CONCLUSION: Juvenile-onset OCD symptom expression is remarkably similar across the lifespan. However, findings also suggest clinically meaningful differences between juveniles and adults. Future work using a prospective design will improve our understanding of course patterns of juvenile-onset OCD.

Macrophage activation by T cells: cognate and non-cognate signals.

Both tumor necrosis factor-alpha and interferon-gamma are involved in the activation of macrophage cytocidal/cytostatic effector function. Recent studies provide evidence that, in non-septic inflammatory disease, T cells may activate macrophages primed by interferon-gamma either by providing tumor necrosis factor-alpha (in soluble or membrane-anchored form) or by inducing macrophage tumor necrosis factor-alpha production by antigen-non-specific cognate interactions. Conversely, T cells may inhibit macrophage activation by producing cytokines that inhibit either tumor necrosis factor-alpha production or interferon-gamma receptor signaling.

Long-term recall of social relationships related to addiction and HIV risk behaviors.

BACKGROUND: Social relationships have been demonstrated as a key predictor of relapse among addicted persons and are likely to be important determinants of HIV risk behaviors also. However, the degree to which this population can reliably and consistently identify important people (IPs) in retrospect has been understudied. METHODS: Using the modified Important People and Activities questionnaire, we investigated to what degree IPs were dropped, added, or retained, and whether data about individual IPs were reported accurately on 6- and 12-month follow up periods using a sample of 50 drug or alcohol abusing participants. RESULTS: We found that IPs were largely retained, and that those retained versus dropped/added differed by their reaction to participant alcohol/drug use, as well as frequency of contact. We further found that there were differences in reliability of data describing specific IPs. While both 6- and 12-month follow up periods led to reliabilities ranging from excellent to fair, we found poorer reliability on responses to recall of "frequency of contact" and "reactions to drinking", as well as "reactions to drug use". CONCLUSION: Future investigations of reliability of social relationships recalled retrospectively should attempt to examine possible systematic biases in addition to the reliability of specific IP data. More sophisticated studies are needed on factors associated with systematic variation in reporting of aspects of social relationships that are associated with addictions or HIV risk outcomes.

Randomized phase II study of two gemcitabine schedules for patients with impaired performance status (Karnofsky performance status

PURPOSE: This randomized phase II study compared two treatment schedules of gemcitabine in patients with non-small-cell lung cancer (NSCLC) and impaired Karnofsky performance status (KP). Primary objectives were to record changes from baseline KP and to assess symptom palliation. Secondary objectives were overall survival, tumor response, and toxicity. PATIENTS AND METHODS: Patients with stage IIIb and IV NSCLC and KP