Inconsistent Counselor Fidelity in Delivering an Evidence-Based Adherence Intervention During a PrEP Trial

AIDS and Behavior - Evidence-based adherence counseling interventions must be delivered with fidelity to ensure that their effectiveness is retained, but little is known regarding how counselors in...     

Immune-mediated changes in actinic keratosis following topical treatment with imiquimod 5% cream

Background  

The objective of this study was to identify the molecular processes responsible for the anti-lesional activity of imiquimod in subjects with actinic keratosis using global gene expression profiling.     

SAG1 is a host-targeted antigen for protection against toxoplasma gondii infection.

We previously reported that SAG1 transgenic (tg) mice have an elevated susceptibility resulting from their inability to elicit strong Th1-based protection against Toxoplasma gondii infection. Here, we demonstrate that SAG1 tg mice were protected against T. gondii infection, characterized by a decline in IFN-gamma levels, following administration of a lethal dose of T. gondii. Moreover, immunization with T. gondii homogenate conferred protection and induced production of IgG, with IgG1 and IgG2a subclasses driven by Th2 and Th1 responses, respectively, in both SAG1 tg and wild-type (wt) mice. IgG titers were significantly higher from day 10 after immunization in wt mice compared to those in SAG1 tg mice. There were no significant differences observed in levels of IgG1 in both groups. However, significantly lower IgG2a titers were measured in the sera from SAG1 tg mice on days 10, 15 and 20. IFN-gamma levels in sera were significantly lower in SAG1 tg mice compared to those in wt mice on day 20 after immunization. When challenged with a lethal dose of the Beverley strain of T. gondii, 80 and 100% survival rates were observed in SAG1 tg and wt mice, respectively, indicating that SAG1 tg mice were protected to a lesser extent from challenge due to the decrease in protective immunity. These results suggest that SAG1 plays a critical role in eliciting protection, hence a target antigen for the development of protective Th1-based responses against T. gondii infection in mice.     

In the absence of endogenous gamma interferon, mice acutely infected with Neospora caninum succumb to a lethal immune response characterized by inactivation of peritoneal macrophages.

Following infection with Neospora caninum, BALB/c mice were shown to be resistant to an acute infection but developed a latent chronic infection. However, BALB/c background gamma interferon (IFN-gamma)-deficient mice were sensitive to the acute infection. Since the immune response in IFN-gamma-deficient mice is scantly known, we examined the function of macrophages, major histocompatibility complex (MHC) class II expression, T-cell responses, and serum cytokine levels in the mice. All IFN-gamma-deficient mice died within 9 days of infection with N. caninum, whereas those treated with exogenous IFN-gamma lived longer. Although N. caninum invaded various organs in both types of mice at the early stage of infection, the parasite was not detected in the brains of resistant hosts until 21 days postinfection (dpi). Peritoneal macrophages from IFN-gamma-deficient mice were activated by exogenous IFN-gamma associated with inhibition of parasite growth and nitric oxide production as were those from BALB/c mice. IFN-gamma-deficient mice failed to increase MHC class II expression on macrophages. Moreover, BALB/c mice induced T-cell proliferation while IFN-gamma-deficient mice did not. However, in vivo treatment with exogenous IFN-gamma induced up-regulated MHC class II expression in IFN-gamma-deficient mice. BALB/c mice treated with an antibody to CD4 showed an increase in morbidity and mortality after parasite infection. In serum, significant levels of IFN-gamma and interleukin-4 (IL-4) were detected in resistant hosts, whereas IL-10 was detected in IFN-gamma-deficient mice. The levels of IL-12 in IFN-gamma-deficient mice were higher than those in BALB/c mice at 7 dpi. The present study indicates that early IFN-gamma production has a crucial role in the activation of peritoneal macrophages for the induction of protective immune responses against N. caninum.     

Immune responses of interferon gamma (IFN-gamma) knock out mice to repeated Haemaphysalis longicornis (Acari: Ixodidae) nymph infestations

To investigate the immunological mechanisms of acquired resistance to tick infestation, interferon gamma (IFN-gamma) deficient mice (IFN-gamma mice) were used to assess interleukin-4 (IL-4) and antibody production levels against tick salivary gland antigen on three successive infestations with Haemoaphysalis longicornis Neumann nymphs. The engorged body weight of the ticks decreased during the second and third infestations. Similar observations were noted in IFN-gamma+/+ mice. However, the engorged body weight of the ticks from IFN-gamma +/+ mice were considerably lower than those from IFN-gamma-/- mice. A marked increase in antibody production during the second and third infestations was observed indicating that IFN-gamma-/- mice could acquire immunological resistance against H. longicornis nymphs. Moreover, IL-4 levels were higher during the first and third infestations but decreased during the second infestation. IL-4 levels were significantly higher in IFN-gamma-/- mice than in IFN-gamma+/+ mice. We have shown here that the statistically significant high IL-4 levels observed in IFN-gamma-/- mice may be a result of type 2 helper cell (Th2) polarization. However, the apparently higher IL-4 levels during the first and third infestations and the notable decline during the second infestation suggest that other cytokines or factors in the host immune system may play a part in regulating IL-4 levels.     

Selective Laser Melting of Maraging Steel Using Synchronized Three-Spot Scanning Strategies

The selective laser melting (SLM) process, a kind of metal additive manufacturing method, can produce parts with complex geometries that cannot be easily manufactured using material removal processes. With increasing industrial applications, there are still issues such as part quality and productivity that need to be resolved. In this study, maraging steel parts fabricated by synchronized three-spot scanning strategies, i.e., lateral spatial (LS) and spatial inline (SiL), are firstly presented. The LS and SiL represent the three-spot offset direction is perpendicular and parallel to the scanning direction, respectively. A laboratory SLM machine equipped with a fiber laser and three-spot module is used to fabricate the maraging steel parts with two scanning strategies, i.e., LS and SiL. The influence of these scanning strategies on the surface roughness, relative density, hardness, molten pool shapes, and microstructures are investigated. The relative density (~99.02%) and surface hardness (~34.0 HRC) are experimentally found to be higher than the SiL by the LS scanning strategy.     

Antigen presentation by murine peritoneal cavity macrophage-derived dendritic cells.

Murine peritoneal cavity macrophage derived dendritic cells (PEC-DC) generated using early growth factors, interleukin 4 and granulocyte-macrophage colony-stimulating factor followed by maturation in interferon-gamma plus either, Toxoplasma lysate antigen (TLA) or lipopolysaccharide, bind TLA by a nonspecific mechanism and continue to express major histocompatibility complex class II antigens after 24 h of culture in vitro. Moreover, the proliferation of CD3+ spleen T cells from mice immunized with Toxoplasma gondii homogenate, induced by PEC-DC-mediated antigen presentation was statistically significant and of consistent amplitude. This accessory function of PEC-DC is antigen specific.     

Canine herpesvirus ORF2 is a membrane protein modified by N-linked glycosylation

Canine herpesvirus (CHV) ORF2, located downstream of the glycoprotein C (gC) gene, has homologues with some of the alphaherpesviruses. To characterize CHV OFR2, a recombinant CHV carrying a LacZ gene in the ORF2 locus, and recombinant vaccinia virus expressing ORF2 protein were constructed. Northern blot analysis revealed ORF2 and a gamma2 class late gene, and its protein product was detectable in CHV-infected cells reacted with ORF2 protein antiserum. Tunicamycin and N-glycosidase F treatment revealed that the ORF2 protein was modified by N-linked glycosylation. Fractionation and immune fluorescence analyses of the CHV-infected cells showed the ORF2 as a membrane protein transportable to the surface of infected cells. In vitro, the ORF2 protein did not affect viral replication and cell-to-cell viral spreading. Present findings represent the first evidence pointing to the CHV ORF2 as a membrane protein modified by an N-linked glycosylation.     

Evaluation of intervention to prevent hypomagnesemia in cervical cancer patients receiving combination cisplatin and radiation treatment

Purpose  The purpose of this study was to evaluate the impact of increasing the magnesium (Mg²⁺) supplementation in the pre- and posthydration of patients receiving cisplatin plus radiation (CisXRT) to prevent chemotherapy-induced hypomagnesemia (CIH) events. Materials and methods  The study was conducted on newly diagnosed cervical cancer patients receiving CisXRT. The first prospective intervention to prevent CIH was to increase the pre- and posthydration Mg²⁺ from 1 to 2 g. After completion of the first intervention, the analysis demonstrated the persistent occurrence of CIH on cycle 3, and later, a second intervention was implemented to increase Mg²⁺ to 3 g in the pre- and posthydration. Patients that failed to complete at least five cycles or received cisplatin in combination with another chemotherapy regimen were excluded from the study. Baseline group included 70 patients that had received CisXRT prior to any changes in magnesium supplementation. Results  There were 62.8% (44/70) and 32.6% (22/70) of patients with episodes of CIH in the baseline and first intervention groups, respectively (P = 0.007). In the second intervention group, a 49.6% decrease in the total number of episodes compared to control group was observed. Patients in the second intervention group showed a 100% improvement incidence of persistent CIH over the two other cohorts (P = 0.001). Conclusions  The increase of Mg²⁺ to 2 g for the initial two cycles and then to 3 g with the third cycle of CisXRT therapy prevented episodes of CIH and decreased associated treatment delays. This is original research that has not been published elsewhere. A preliminary report was presented as a poster at the HOPA/ISOPP Joint Meeting June 20th, 2008.