Psychometric analysis of the Life Worries Scale for a new generation of sexual minority men: The P18 Cohort Study.

OBJECTIVE: Sexual minority men (SMM) in the United States continue to experience adverse health problems and psychosocial burdens. However, there is limited psychometric research seeking to quantify the life worries of this population. Informed by syndemic theory, the Life Worries Scale (LWS) was developed to measure the concerns of young SMM. METHOD: Analyses of the scale were undertaken using baseline data (n = 665) from an ongoing cohort study of emerging adult, SMM. RESULTS: Exploratory factor analyses (EFA) of an initial set of 24 Likert-type items, followed by confirmatory factor analysis (CFA) and an exploratory structural equation model (ESEM), indicated a structure consisting of 6 domains of worries: financial stability, social stability, self esteem, loneliness, physical appearance, and physical health. These 6 subscales were highly correlated and also demonstrated high levels of internal consistency. Differences in life worries were noted across demographic states, specifically HIV serostatus, sexual attraction, housing status, and self-rated health. High levels of association were also detected between all 6 subscales with both depression and PTSD, while significant correlations were detected between suicidality and both self esteem and loneliness related worries. CONCLUSIONS: The results of our analyses provide evidence for the strong psychometric characteristics of the LWS. This newly developed instrument should be utilized in research to examine the extent to which life worries explain health outcomes and risk behaviors in sexual minority males, and may be potentially extended for use in other populations. (PsycINFO Database Record

Associations of Perceived Parental Psychopathology with Mental Health Burden and Lifetime Drug Use in Gay, Bisexual, and other YMSM: The P18 Cohort Study.

Parental mental health may be a critical component in understanding the overlapping health burdens of mental health symptomatology and drug use in young men who have sex with men (YMSM), yet studies of YMSM have not fully examined these associations. To understand these relationships, data drawn from a study of gay, bisexual, and other YMSM were used to examine associations between perceived parental psychopathology and the health of YMSM. Findings suggest that YMSM reporting at least one parent with perceived depression, manic depression, schizophrenia, or antisocial behavior anytime during their childhoods were more likely to report higher levels of both depressive symptomatology and post-traumatic stress disorder (PTSD) than those reporting no perception of any of these psychopathologies in their parents. Number of different drugs used in one's life were higher among participants who perceived at least one parent as depressed. Mediation analyses indicated that the relationship between perceived parental depression and lifetime drug use of YMSM was mediated both by YMSM depression and YMSM PTSD. These results suggest that parental psychopathology plays an important role in the health of sexual minority men, a population with elevated levels of mental health burden and drug use across the lifespan.

Feasibility and Acceptability of Global Positioning System (GPS) Methods to Study the Spatial Contexts of Substance Use and Sexual Risk Behaviors among Young Men Who Have Sex with Men in New York City: A P18 Cohort Sub-Study.

BACKGROUND: No global positioning system (GPS) technology study has been conducted among a sample of young gay, bisexual, and other men who have sex with men (YMSM). As such, the purpose of this study was to evaluate the feasibility and acceptability of using GPS methods to understand the spatial context of substance use and sexual risk behaviors among a sample of YMSM in New York City, a high-risk population. METHODS: Data came from a subsample of the ongoing P18 Cohort Study (n = 75). GPS feasibility and acceptability among participants was measured with: 1) a pre- and post-survey and 2) adherence to the GPS protocol which included returning the GPS device, self-report of charging and carrying the GPS device as well as objective data analyzed from the GPS devices. Analyses of the feasibility surveys were treated as repeated measures as each participant had a pre- and post-feasibility survey. When comparing the similar GPS survey items asked at baseline and at follow-up, we present percentages and associated p-values based on chi-square statistics. RESULTS: Participants reported high ratings of pre-GPS acceptability, ease of use, and low levels of wear-related concerns in addition to few concerns related to safety, loss, or appearance, which were maintained after baseline GPS feasibility data collection. The GPS return rate was 100%. Most participants charged and carried the GPS device on most days. Of the total of 75 participants with GPS data, 75 (100%) have at least one hour of GPS data for one day and 63 (84%) had at least one hour on all 7 days. CONCLUSIONS: Results from this pilot study demonstrate that utilizing GPS methods among YMSM is feasible and acceptable. GPS devices may be used in spatial epidemiology research in YMSM populations to understand place-based determinants of health such as substance use and sexual risk behaviors.

Temporal relations between methamphetamine use and HIV seroconversion in gay, bisexual, and other men who have sex with men.

Data from a cross-sectional study of gay, bisexual, and other men who have sex with men who were active methamphetamine users were analyzed to assess temporal relations between HIV seroconversion and initiation of methamphetamine use. Of the 100 men, 58 reported being HIV-positive. Most HIV-positive participants (65%) initiated methamphetamine use after seroconverting. Among those who initiated use before seroconversion, 8 years elapsed between onset of use and time of infection. Findings suggest the need to develop nuanced and targeted interventions aimed at disentangling the "meth-sex" link in this population. Findings also suggest use of the drug as a coping mechanism for those living with HIV.

R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6.

The R-Spondin (RSpo) family of secreted proteins act as potent activators of the Wnt/beta-catenin signaling pathway. We have previously shown that RSpo proteins can induce proliferative effects on the gastrointestinal epithelium in mice. Here we provide a mechanism whereby RSpo1 regulates cellular responsiveness to Wnt ligands by modulating the cell-surface levels of the coreceptor LRP6. We show that RSpo1 activity critically depends on the presence of canonical Wnt ligands and LRP6. Although RSpo1 does not directly activate LRP6, it interferes with DKK1/Kremen-mediated internalization of LRP6 through an interaction with Kremen, resulting in increased LRP6 levels on the cell surface. Our results support a model in which RSpo1 relieves the inhibition DKK1 imposes on the Wnt pathway.

R-spondin1, a novel intestinotrophic mitogen, ameliorates experimental colitis in mice.

BACKGROUND & AIMS: R-spondin 1 (Rspo1) is a novel epithelial mitogen that stimulates the growth of mucosa in both the small and large intestine. METHODS: We investigated the therapeutic potential of Rspo1 in ameliorating experimental colitis induced by dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) as well as nonsteroidal anti-inflammatory drug-induced colitis in interleukin (IL)-10-deficient mice. RESULTS: Therapeutic administration of recombinant Rspo1 protein reduced the loss of body weight, diarrhea, and rectal bleeding in a mouse model of acute or chronic DSS-induced colitis. Histologic evaluation revealed that Rspo1 improved mucosal integrity in both villus and/or crypt compartments in the small intestine and colon by stimulating crypt cell growth and mucosal regeneration in DSS-treated mice. Moreover, Rspo1 significantly reduced DSS-induced myeloperoxidase activity and inhibited the overproduction of proinflammatory cytokines, including tumor necrosis factor-alpha, IL-1alpha, IL-6, interferon-gamma, and granulocyte-macrophage colony-stimulating factor, in mouse intestinal tissue, indicating that Rspo1 may reduce DSS-induced inflammation by preserving the mucosal barrier function. Likewise, Rspo1 therapy also alleviated TNBS-induced interstitial inflammation and mucosal erosion in the mouse colon. Furthermore, Rspo1 substantially decreased the histopathologic severity of chronic enterocolitis by repairing crypt epithelium and simultaneously suppressing inflammatory infiltration in piroxicam-exposed IL-10(-/-) mice. Endogenous Rspo1 protein was localized to villus epithelium and crypt Paneth cells in mouse small intestine. CONCLUSIONS: Our results show that Rspo1 may be clinically useful in the therapeutic treatment of inflammatory bowel disease by stimulating crypt cell growth, accelerating mucosal regeneration, and restoring intestinal architecture.

The lymphoid cell surface receptor NTB-A: a novel monoclonal antibody target for leukaemia and lymphoma therapeutics.

NTB-A is a CD2-related cell surface protein expressed primarily on lymphoid cells including B-lymphocytes from chronic lymphocytic leukaemia (CLL) and lymphoma patients. We have generated a series of monoclonal antibodies (mAbs) against NTB-A and assessed their therapeutic potential for CLL. Selective mAbs to NTB-A were further tested in functional complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicty (ADCC) assays in cell lines and B lymphocytes freshly isolated from CLL patients. While lower levels of NTB-A were detected in T and natural killer (NK) cells, CDC activity was demonstrated primarily in B cells isolated from CLL patients and B lymphoma cell lines. Knockdown of NTB-A by small interfering RNA in target cells results in lower cytotoxicity, demonstrating the specificity of the mAbs. Furthermore, anti NTB-A mAbs demonstrated anti-tumour activity against CA46 human lymphoma xenografts in nude mice and against systemically disseminated Raji human lymphoma cells in severe combined immunodeficient mice. Taken together, these results demonstrate NTB-A as a potential new target for immunotherapy of leukaemia and lymphomas.

Alfimeprase: a novel recombinant direct-acting fibrinolytic.

Alfimeprase is a recombinant, direct-acting fibrinolytic zinc metalloprotease. Alfimeprase has direct proteolytic activity primarily against the fibrin(ogen) Aalpha chain. Alfimeprase is covalently bound and neutralised by serum alpha(2)-macroglobulin, a prevalent mammalian protease inhibitor. Preclinical pharmacology studies have shown that fibrinolysis with alfimeprase is up to sixfold more rapid than with select plasminogen activators, such as tissue-type plasminogen activator and urokinase. Alfimeprase directly delivered to a site of thrombosis has the potential to be a fast and effective fibrinolytic, which does not generate the systemic lytic state seen with plasminogen activators that is associated with major bleeding, including intracerebral haemorrhage. Phase I and II studies in individuals with arterial or venous thrombotic events indicate that alfimeprase is active and generally well tolerated.