Castration immunoregulates toll-like receptor-4 in male bladder cancer

International Urology and Nephrology - Among diverse Pattern Recognition Receptors (PRRs), Toll-like receptor-4 (TLR-4) is a key urothelial trigger for innate immune response impacting urothelial...     

LALF<Subscript>32-51</Subscript>-E7 therapeutic vaccine induces antitumor immunity against human papillomavirus type 16 E7-expressing murine tumor metastases in the lungs

One important goal of cancer immunotherapy is to prevent and treat tumor metastasis. We have previously reported the significant antitumor effect induced by the immunization with our human papillomavirus therapeutic protein-based vaccine (LALF_32-51-E7) without adjuvant and admixed with clinically relevant adjuvants in the subcutaneous TC-1 tumor challenge model. In the present study, we evaluated the efficacy of the above mentioned vaccine formulations in controlling the hematogenous spread of TC-1 tumor cells using a more tumourigenic clone named TC-1* and other intravenous injection site less stressful than the tail vein. We generated a lung metastasis model by injecting TC-1* cells into the retro-orbital venous sinus and this is the first study describing it. Also, this is the first study that demonstrates the efficacy of the immunization with LALF_32-51-E7 without adjuvant and admixed with VSSP or Al(OH)₃ in controlling metastatic tumors increasing the survival of the mice. Our TC-1 lung metastasis model can be used to test the efficacy of other immunotherapeutic strategies based on E6/E7 antigens.     

HIV discrimination and the health of women living with HIV

Women living with HIV are especially vulnerable to discrimination because of the stigma associated with the disease, as well as their race, gender and class status. To investigate the association between self-reported HIV discrimination and health outcomes among African- American and white women living with HIV, 366 women living with HIV were recruited from HIV/AIDS clinics in Georgia and Alabama. In this cross-sectional study, participants completed an interview that assessed self-reported HIV discrimination and depressive symptomatology, suicidal ideation, self-esteem, stress, quality of life, sexual health and HIV/AIDS related health care seeking. Nearly a sixth of the sample reported experiencing HIV discrimination. Women reporting HIV discrimination had higher mean scores for stress, suicidal ideation, depressive symptoms, number of unprotected sexual episodes; they had lower mean scores for self-esteem, and quality of life, and were more likely to have not sought medical care for HIV/AIDS. In race-specific analyses, none of the relationships between HIV discrimination and health outcomes were significant for white women. African-American women who reported HIV discrimination had higher mean scores for stress, suicidal ideation, depressive symptoms, number of unprotected sexual episodes; they had lower mean scores for self-esteem, and quality of life, and were more likely not to have sought medical care for HIV/AIDS. The findings indicated that HIV discrimination adversely affects women's mental, sexual and physical health. However, separate race-specific analyses indicated that compared to white women, African-American women were markedly more likely to experience the adverse affects of HIV discrimination. Eradication of HIV discrimination remains an important public health priority.     

Adaptation and validation of indicators concerning the sterilization process of supplies in Primary Health Care services

OBJECTIVES:

to adapt and validate, by expert consensus, a set of indicators used to assess the sterilization process of dental, medical and hospital supplies to be used in PHC services.

METHOD:

qualitative methodological study performed in two stages. The first stage included a focal group composed of experts to adapt the indicators to be used in PHC. In the second stage, the indicators were validated using a 4-point Likert scale, which was completed by judges. A Content Validity Index of ≥ 0.75 was considered to show approval of the indicators.

RESULTS:

the adaptations implemented by the focal group mainly referred to the physical structure, inclusion of dental care professionals, inclusion of chemical disinfection, and replacement of the hot air and moist heat sterilization methods. The validation stage resulted in an index of 0.96, which ranged from 0.90 to 1.00, for the components of the indicators.

CONCLUSION:

the judges considered the indicators after adaptation to be validated. Even though there may be differences among items processed around the world, there certainly are common characteristics, especially in countries with economic and cultural environments similar to Brazil. The inclusion of these indicators to assess the safety of healthcare supplies used in PHC services should be considered.     

Prospective,Randomized Trial of Higher Goal Hemoglobin after Subarachnoid Hemorrhage

Background and Purpose  

In patients with subarachnoid hemorrhage (SAH), higher hemoglobin (HGB) has been associated with better outcomes, but packed red blood cell (PRBC) transfusions with worse outcomes. We performed a prospective pilot trial of goal HGB after SAH.     

Abnormal APP processing in platelets of patients with Alzheimer’s disease: correlations with membrane fluidity and cognitive decline

Rationale Previous studies have implicated platelet amyloid precursor protein (APP) as a candidate biomarker for Alzheimer’s disease (AD). Platelets contain more than 95% of the circulating APP and enclose the enzymatic machinery for the APP metabolism yielding both soluble APP and amyloid-β peptides. Objectives The objective of this study is to compare the ratio of 130- to 110-kDa fragments of APP in platelets from patients with AD, mild cognitive impairment (MCI), and elderly controls. Materials and methods After subjects were grouped according to diagnosis, APP ratio in platelets was evaluated by means of Western blot analysis. Results The APP ratio was significantly lower in AD patients (1.01 ± 0.21) as compared to controls (1.24 ± 0.21, p = 0.001) and MCI patients (1.18 ± 0.21, p = 0.027), but no significant differences were found between MCI and controls (p = 0.904). In addition, we found positive correlations between the APP ratio and 1,6-diphenyl-1,3,5-hexatriene anisotropy (r = 0.3, p = 0.01), as well as with certain parameters of cognitive decline, namely, the mini-mental state examination score (r = 0.33, p = 0.003), the total Cambridge cognitive test (CAMCOG) score (r = 0.37, p = 0.001), and the score on the memory subscale of the CAMCOG (r = 0.38, p = 0.001). Conclusions The pattern of platelet APP fragments was altered in patients with AD but not in patients with MCI. The alteration of APP fragments was correlated with membrane fluidity and the cognitive decline.     

Novel treatments for systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease that is associated with the production of autoantibodies, and with considerable morbidity and mortality. There has been much interest in developing more specific therapies for this disease, which is currently managed with immunosuppressive drugs, predominantly corticosteroids, azathioprine, methotrexate and cyclophosphamide, in combination with hydroxychloroquine. Mycophenolate mofetil has been demonstrated to be as efficacious as cyclophosphamide in patients with lupus nephritis, and is being used increasingly in the clinic despite not being licensed for this indication. Novel methods of reducing autoantibody formation in SLE include the use of mAbs that modulate and/or deplete B-cells (anti-CD22 and anti-CD20 antibodies, respectively), or that interfere with the stimulatory effects of the soluble factor B-lymphocyte stimulator (anti-BLys antibodies). Alternative approaches include the use of atacicept (Merck Serono), a transmembrane activator and calcium modulator ligand interactor (TACI)-Ig fusion protein, which inhibits B-cell stimulation by binding to BLys and a profileration-inducing ligand (APRIL), or toleragens such as abetimus. Blocking costimulatory molecule interactions, such as the CD40-CD40 ligand interaction with mAbs and the CD28-B7 interaction with a soluble cytotoxic T-lymphocyte antigen 4 (CTLA-4)-IgG1 construct (abatacept), has also been attempted as a therapeutic strategy for SLE. The most promising strategy for a new drug for SLE is belimumab (Human Genome Sciences/GlaxoSmithKline), an anti-BLys antibody, as two phase III clinical trials with this drug recently met their primary endpoints. In this review, these novel approaches to the treatment of SLE, including the potential of targeting cytokine pathways involved in autoimmunity, are discussed.