Presence of Symptomatology and VA Service Seeking Among OEF/OIF/OND Veterans with Complicated Grief

Posttraumatic stress disorder (PTSD) and complicated grief (CG) are debilitating disorders associated with numerous negative health concerns. PTSD has been widely studied among Veteran populations, however, few studies have evaluated CG. The current study examined 1122 returning Veterans following enrollment into the VA San Diego Healthcare System (VASDHS). Veterans were classified into four groups based on self-reported symptoms: (1) CG alone (n = 26); (2) PTSD alone (n = 112); (3) both CG and PTSD (n = 99), and (4) neither CG or PTSD (Veteran controls; n = 554). This study aimed to (1) evaluate group differences in baseline demographic, physical, and mental health variables (baseline variables); (2) evaluate group differences in use of physical healthcare, mental healthcare, and emergency services (healthcare services) within the first six months following VASDHS enrollment; and (3) evaluate the predictive utility of baseline variables on use of healthcare services within the first six months following VASDHS enrollment. Regression analyses (multiple, binary logistic, multinomial logistic, and negative binomial) were used. Screening positive for both CG and PTSD was associated with the greatest severity of physical and mental health symptoms, followed by PTSD alone, CG alone, and Veteran controls. Screening positive for both CG and PTSD and PTSD alone was associated with greater use of healthcare services compared to other groups. Baseline variables, including branch of military service, positive TBI screen, greater generalized anxiety symptoms, greater insomnia symptoms, greater physical health symptoms, greater pain interference, worse mental health functioning, less resilience, and better physical health functioning predicted greater use of healthcare services. These findings supplement the growing body of literature documenting the negative health impact of PTSD and add to it the importance of considering CG in the overall health and health-utilization of returning Veterans. Results suggest that Veterans with PTSD are more likely to use healthcare services compared to Veterans without PTSD. Results may also suggest that Veterans with CG may underutilize healthcare services compared to other groups. This highlights the importance of routinely screening for CG in Veteran populations, and is relevant to understanding and improving access to healthcare services for Veterans with CG

Evaluating a Collaborative iPad Game's Impact on Social Relationships for Children with Autism Spectrum Disorder

This article describes how collaborative assistive technologies, housed on off-the-shelf, low-cost platforms such as the iPad, can be used to facilitate social relationships in children with autism spectrum disorder (ASD). Through an empirical study of the use of a collaborative iPad game, Zody, we explore how assistive technologies can be used to support social relationships, even without intervention from adults. We discuss how specific design choices can encourage three levels of social relationship: membership, partnership, and friendship. This work contributes to research on both assistive technologies and collaborative gaming through a framework that describes how specific in-game elements can foster social skill development for children with ASD

Mice transgenic for CD4-specific human CD4, CCR5 and cyclin T1 expression: a new model for investigating HIV-1 transmission and treatment efficacy.

Mice cannot be used to evaluate HIV-1 therapeutics and vaccines because they are not infectible by HIV-1 due to structural differences between several human and mouse proteins required for HIV-1 entry and replication including CD4, CCR5 and cyclin T1. We overcame this limitation by constructing mice with CD4 enhancer/promoter-regulated human CD4, CCR5 and cyclin T1 genes integrated as tightly linked transgenes (hCD4/R5/cT1 mice) promoting their efficient co-transmission and enabling the murine CD4-expressing cells to support HIV-1 entry and Tat-mediated LTR transcription. All of the hCD4/R5/cT1 mice developed disseminated infection of tissues that included the spleen, small intestine, lymph nodes and lungs after intravenous injection with an HIV-1 infectious molecular clone (HIV-IMC) expressing Renilla reniformis luciferase (LucR). Furthermore, localized infection of cervical-vaginal mucosal leukocytes developed after intravaginal inoculation of hCD4/R5/cT1 mice with the LucR-expressing HIV-IMC. hCD4/R5/cT1 mice reproducibly developed in vivo infection after inoculation with LucR-expressing HIV-IMC which could be bioluminescently quantified and visualized with a high sensitivity and specificity which enabled them to be used to evaluate the efficacy of HIV-1 therapeutics. Treatment with highly active anti-retroviral therapy or one dose of VRC01, a broadly neutralizing anti-HIV-1 antibody, almost completed inhibited acute systemic HIV-1 infection of the hCD4/R5/cT1 mice. hCD4/R5/cT1 mice could also be used to evaluate the capacity of therapies delivered by gene therapy to inhibit in vivo HIV infection. VRC01 secreted in vivo by primary B cells transduced with a VRC01-encoding lentivirus transplanted into hCD4/R5/cT1 mice markedly inhibited infection after intravenous challenge with LucR-expressing HIV-IMC. The reproducible infection of CD4/R5/cT1 mice with LucR-expressing HIV-IMC after intravenous or mucosal inoculation combined with the availability of LucR-expressing HIV-IMC expressing transmitted/founder and clade A/E and C Envs will provide researchers with a highly accessible pre-clinical in vivo HIV-1-infection model to study HIV-1 acquisition, treatment, and prevention

In vivo HIV-1 infection of hCD4/R5/cT1 mice is inhibited by antiretroviral therapy or by treatment with a broadly neutralizing antibody.

<p>(A) One group of hCD4/R5/cT1 mice (n = 4 mice) was untreated and another group (n = 4 mice) was started on HAART administered in their drinking water. Five days later these mice were infected with NL4-LucR.T2A-Bal.ecto by intrasplenic injection. (B) hCD4/R5/cT1 mice were untreated (n = 5 mice) or treated with one intravenous dose (1 mg) of VRC01 (n = 5 mice). The next day, the mice were infected with NL4-LucR.T2A-Bal.ecto by intrasplenic injection. One week later, HIV-1 infection was quantified by measuring LucR activity in the splenic lysates. The average LucR activity for the mice in each group +/− STE is shown.</p

HIV-1 infection of hCD4/R5/cT1 mice is inhibited by VRC01 antibody secreted in vivo by transduced B cells.

<p>hCD4/R5/cT1 mice were uninjected (n = 4 mice) or intrasplenicly injected with highly purified primary B cells which were either untransduced (n = 4 mice) or transduced with the VRC01-expressing lentivirus (n = 4 mice). Two days later, the mice were all inoculated intravenously with NL-LucR-T2A-Bal.ecto. Seven days later, the mice were sacrificed. (<b>A</b>) The level of VRC01 antibody in the serum was determined by an ELISA assay (<b>B</b>) The LucR activity in the mouse spleens was quantified. The average VRC01 serum antibody levels and LucR activity in the spleens for the mice in each group +/− STE is shown.</p

hCD4/R5/cT1 mice develop disseminated HIV infection after intravenous injection. hCD4/R5/cT1 mice and wild type mice (n = 5 mice/group) were intravenously injected with NL4-LucR.T2A-Bal.ecto.

<p>One week later, mononuclear cells were harvested from the mouse spleens, small intestines, iliac lymph nodes and lungs. The average LucR activity in the cellular lysates from the indicated tissues of the hCD4/R5/cT1 mice and wild-type mice in each group ± STE is shown.</p

In vivo HIV-1 infection of hCD4/R5/cT1 mice. (A) hCD4/R5/cT1 mice and wild-type mice were intrasplenicly injected with NL4-LucR.T2A-Bal.ecto.

<p>LucR activity in the splenic lysates from the mice was measured at 1 week, 2 weeks and 4 weeks (n = 5–8 mice/group) after infection. For all experiments, the average LucR activity in the spleens of the mice in each group ± STE is shown. (B) hCD4/R5/cT1 mice (n = 2) or a control C57BL/6 mouse were intrasplenicly injected with NL4-LucR.T2A-Bal.ecto and 7 days later the spleens were harvested. After ex vivo injection with RediJect Coelenterazine h, bioluminescent and grey-scale images of isolated spleens from the infected hCD4/R5/cT1 mouse spleens (left and center) and the control C57BL/6 mouse (right) were captured with the IVS Spectrum imager and bioluminescence intensity represented in a pseudocolor image indicating photon counts/second are shown. (C) HIV-1 RNA levels in the plasma of hCD4/R5/cT1 and wild-type mice (n = 3 mice/group) were quantified at 2 and 3 weeks after intrasplenic injection with NL4-LucR.T2A-Bal.ecto. (D) Five days after hCD4/R5/CT1 mice or wild-type mice were intravaginally challenged with NL4-LucR.T2A-Bal.ecto (n = 5 mice/group), the LucR levels in leukocytes isolated from the vaginal tissues were determined.</p

Construction of hCD4/R5/cT1 mice and evaluation of transgene expression.

<p>(<b>A</b>) Schematic representation of the human CD4/CCR5 and cyclin T1 transgene constructs. E4/P4, murine CD4 enhancer/promoter; N, Xb, Xh, Cl, Sc, B, and S, restriction enzyme sites for NotI, XbaI, Xho1, ClaI, SacI, BamHI and SalI, respectively; SVpA, SV40 polyadenylation signal. (<b>B</b>) Transmission of the human CD4 and CCR5 or cyclin T1 in the transgenic mouse founders was determined by PCR. DNA was extracted from the tails of the indicated transgenic founder mice and integrated human CD4, CCR5 or cyclin T1 genes were detected by PCR amplification with primer pairs specific for human CD4, CCR5 and cyclin T1, respectively. (<b>C</b>) Expression of the human cyclin T1 transgene in the spleens and thymuses of founder 479 progeny mice was detected by immunoblotting with a polyclonal antibody specific for human cyclin T1. Lysate from spleens from a JRCSF/hu-CycT1 mouse and a wild-type littermate mice were run as positive and negative controls respectively and equivalent protein loading was demonstrated by immunoblotting with a polyclonal antibody specific for mouse actin.</p