Interferon-γ (IFNγ) plays various roles in the pathogenesis of HIV/AIDS. In an HIV-1 infected individual, the production of IFNγ is detected as early as the acute phase and continually detected throughout the course of infection. Initially produced to clear the primary infection, IFNγ together with other inflammatory cytokines are involved in establishing a chronic immune activation that exacerbates clinical diseases associated with AIDS. Unlike Type 1 IFNs, IFNγ has no direct antiviral activity against HIV-1 in primary cultures, as supported by the in vivo findings of IFNγ therapy in infected subjects. Results from both in vitro and ex vivo studies show that IFNγ can instead enhance HIV-1 replication and its associated diseases, and therapies aimed at decreasing its production are under consideration. On the other hand, IFNγ has been shown to enhance cytotoxic T lymphocytes and NK cell activities against HIV-1 infected cells. These activities are important in controlling HIV-1 replication in an individual and will most likely play a role in the prophylaxis of an effective vaccine against HIV-1. Additionally, IFNγ has been used in combination with HIV-1 vaccine to augment antiviral immunity. Technological advancements have focused on using IFNγ as a biological marker to analyze the type(s) of immunity generated by candidate HIV vaccines and the levels of immunity restored by anti-retroviral drug therapies or novel immunotherapies. Hence, in addition to its valuable ancillary role as a biological marker for the development of effective HIV-1 prophylactic and therapeutic strategies, IFNγ has a vital role in promoting the pathogenesis of HIV.

The EphA2 receptor tyrosine kinase is frequently overexpressed and functionally altered in malignant cells and thus provides opportunities for selective targeting of tumor cells.

Multisite pain, or pain that occurs simultaneously at >1 anatomical site, is more prevalent than single-site pain. While multisite pain affects over half of older adults, it remains an understudied pain entity that may have important functional implications in an aging population. Greater understanding of this complex pain entity from a biopsychosocial perspective is critical for optimizing clinical and functional outcomes in older adults with pain. Therefore, the primary purpose of this review is to summarize the relationship between multisite pain and functional outcomes in older adults to further elucidate the impact of multisite pain as a distinct entity within this population. A comprehensive literature search revealed 17 peer-reviewed articles. Multisite pain in older individuals is associated with reductions in several physical function domains: 1) lower-extremity mobility; 2) upper-extremity impairments; 3) balance and increased fall risk; and 4) general disability and poor physical function. Further, multisite pain in older individuals is associated with psychological dysfunction (eg, anxiety and depressive symptoms) and social factors (eg, income and education). Overall, this review highlights the scant literature investigating the functional implications of multisite pain in an aging population. Further, while multisite pain appears to have functional consequences, the neurobiological mechanisms contributing to this relationship are unknown. Thus, how this pain characteristic may contribute to the variability in pain-related functional outcomes among older adults is not clear. Future investigations are strongly warranted to advance the understanding of multisite pain and its broad impact on physical and psychosocial function in older adults.

Homozygous m-opioid receptor (MOR) knockout (KO) mice developed on a chimeric C57B6/129SV background lack morphine-induced antinociception, locomotion and reward. Therefore it appears that MOR largely mediates these morphine actions. However, one factor that could affect the extent of knockout deficits in morphine-induced behavior is the genetic background against which the gene deletion is expressed. To examine the effect of genetic background chimeric C57B6/129SV MOR knockout mice from the 15th generation of those developed in our laboratory were backcrossed for 10 successive generations with C57BL/6 mice, a strain which is more sensitive to many of the properties of morphine, to produce congenic MOR (con-MOR) KO mice. Heterozygote conMOR KO mice display attenuated morphine locomotion and reduced morphine analgesia compared to wild-type mice. Homozygote con-MOR KO mice display baseline hyperalgesia, no morphine place preference, no morphine analgesia and no morphine locomotion. These results are not qualitatively different from those observed in the MOR KO strain with a chimeric C57B6/129SV background, and suggest that although the strain has separate influences on these functions, it does not substantially interact with deletion of the m opiate receptor gene.Keywords: Analgesia, conditioned place preference, congenic, locomotion, transgenic knockout mice This article is the material of the US Government, and can be produced by the public at will. m-opioid receptor (OPRM1) knockout (KO) mice that we and others have created on a number of genetic backgrounds display substantial alterations in basal and/or morphineinduced phenotypes involving nociceptive, locomotor control and reward systems (Fuchs et

The parasitic nematode Angiostrongylus cantonensis is a major cause of eosinophilic meningitis in humans, and has been documented in other incidental hosts such as birds, horses, dogs and non-human primates. It is endemic in Hawaii, and there have been sporadic reports in the southern continental United States. This parasite uses rats as definitive hosts and snails as intermediate hosts. In this study, we collected potential definitive and intermediate hosts throughout Florida to ascertain the geographic distribution in the state: Rats, environmental rat fecal samples, and snails were collected from 18 counties throughout the state. Classical diagnostics and morphological identification, along with molecular techniques were used to identify nematode species and confirm the presence of A. cantonensis.Of the 171 Rattus rattus collected, 39 (22.8%) were positive for A. cantonensis, and 6 of the 37 (16.2%) environmental rat fecal samples collected in three of the surveyed counties were also positive for this parasite by real time PCR. We examined 1,437 gastropods, which represented 32 species; 27 (1.9%) were positive for A. cantonensis from multiple sites across Florida. Three non-native gastropod species, Bradybaena similaris, Zachrysia provisoria, and Paropeas achatinaceum, and three native gastropod species, Succinea floridana, Ventridens demissus, and Zonitoides arboreus, which are newly recorded intermediate hosts for the parasite, were positive for A. cantonensis. This study indicates that A. cantonensis is established in Florida through the finding of adult and larval stages in definitive and intermediate hosts, respectively, throughout the state. The ability for this historically subtropical nematode to thrive in a more temperate climate is alarming, however as the climate changes and average temperatures rise, gastropod distributions will probably expand, leading to the spread of this parasite in more temperate areas. Through greater awareness of host species and prevalence of A. cantonensis in the United States, potential accidental infections may be avoided.

A, granzyme B). The epitopes inducing polyfunctional T-cell activities were highly conserved among human, simian, feline, and ungulate lentiviruses, which indicated that these epitopes are evolutionarily conserved. These results suggest that FIV peptides could be used in an HIV-1 vaccine.

The importance of vaccine-induced T-cell immunity in conferring protection with prototype and commercial FIV vaccines is still unclear. Current studies performed adoptive transfer of T cells from prototype FIV-vaccinated cats to partial-to-complete feline leukocyte antigen (FLA)-matched cats a day before either homologous FIVPet or heterologous-subtype pathogenic FIVFC1 challenge. Adoptive-transfer (A–T) conferred a protection rate of 87% (13 of 15, p<0.001) against FIVPet using FLA-matched T cells, whereas all 12 control cats were unprotected. Furthermore, A-T conferred protection rate of 50% (6 of 12, p<0.023) against FIVFC1 using FLA-matched T cells, whereas all 8 control cats were unprotected. Transfer of FLA-matched T and B cells demonstrated that T cells are needed to confer A-T protection. In addition, complete FLA-matching and addition of T-cell numbers >13×106 cells were required for A-T protection against FIVFC1 strain, reported to be a highly pathogenic virus resistant to vaccine-induced neutralizing-antibodies. The addition of FLA-matched B cells alone was not protective. The poor quality of the anti-FIV T-cell immunity induced by the vaccine likely contributed to the lack of protection in an FLA-matched recipient against FIVFC1. The quality of the immune response was determined by the presence of high mRNA levels of cytolysin (perforin) and cytotoxins (granzymes A, B, and H) and T helper-1 cytokines (interferon-γ [IFNγ] and IL2). Increased cytokine, cytolysin and cytotoxin production was detected in the donors which conferred protection in A-T studies. In addition, the CD4+ and CD8+ T-cell proliferation and/or IFNγ responses to FIV p24 and reverse transcriptase increased with each year in cats receiving 1X-3X vaccine boosts over 4 years. These studies demonstrate that anti-FIV T-cell immunity induced by vaccination with a dual-subtype FIV vaccine is essential for prophylactic protection against AIDS lentiviruses such as FIV and potentially HIV-1.

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