Effects of Animal-Assisted Therapy on Communication, Agitation and General Health in Individuals with Dementia Living in Long-Term Care Facilities and the Secondary Effects on Their Caregivers.

The use of animals for therapeutic purposes has existed for centuries. However, it was not until recently that people realized the human-animal interaction has potential effects on our overall health. Human-animal interaction positively impacts humans\u27 social, emotional, and cognitive functions (Woods et al., 2005). This research encompasses two studies. Both studies examined the therapeutic effects of an animal-assisted therapy (AAT) dog presence on communication abilities and agitation of individuals with mild to severe dementia residing in a long-term care facility. Study 1 examined agitated behaviors, communications, and social interactions of older adults with dementia living in a long-term care facility using a homemade General Health Survey (GHS), Agitated Behavioral Scale (ABS), and a Picture Recognition Activity (PRA). Study 1 showed statistically significant decreases in agitated behaviors and a statistically significant increase in social interaction and picture recognition with vs without AAT. Study 2 is a retrospective study completed on the nursing staff to examine the potential indirect effects of ATT on job satisfaction and work-related stress levels while caring for individuals with dementia in Study 1. Study 2 indicated an increase in job satisfaction and decreased job-related stress as reported by the nursing staff when working with dementia participants who had received AAT. Study 1 and Study 2 demonstrated an increase in overall communication among all five residents with dementia on days when animal-assisted therapy was present

Influencia del lugar de origen en la utilización de pruebas de cribado de cáncer ginecológico en España

OBJETIVO: Analizar la asociación entre el área geográfica de procedencia en el uso de las citologías y la mamografía. MÉTODOS: Los datos analizados proceden Encuesta Nacional de Salud de España-2006 dirigida a población mayor de 16 años. La Encuesta incluye 13.422 mujeres. Las variables dependientes fueron realización de una mamografía y de una citología vaginal, ambos en los últimos 12 meses. La medida de asociación fue el odds ratio con intervalo de confianza al 95% calculado por regresión logística. RESULTADOS: Tomando como referencia la población española, la probabilidad de realizarse una mamografías entre las mujeres procedentes de África fue 0,36 (IC95% 0,21;0,62) veces menor; Europa del Este 0,40 (IC95% 0,22;0,74) veces menor; Europa Occidental, EEUU y Canadá, 0,60 (IC95% 0,43; 0,84) veces menor y América Central / Sur 0,64 (IC95% 0,52;0,81) veces menor. En relación a la prevención de cáncer de cervix, probabilidad de realizarse una citología entre las mujeres Europa del Este fue 0,38 (IC95% 0,28;0,50) veces menor que la población española, África 0,47 (IC95%:0,33;0,67) veces menor y Europa Occidental, EEUU y Canadá 0,61 (IC95% 0,46;0,81) veces menor. Dichas asociaciones fueron independientes de la edad, indicadores socioeconómicos, estado de salud y cobertura sanitaria. CONCLUSIONES: Las mujeres inmigrantes hacen menor uso de los programas de cribado que las mujeres autóctonas. Este dato podría reflejar dificultades de acceso a los programas preventivos

Predictors of low cervical cancer screening among immigrant women in Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>Disparities in cervical cancer screening are known to exist in Ontario, Canada for foreign-born women. The relative importance of various barriers to screening may vary across ethnic groups. This study aimed to determine how predictors of low cervical cancer screening, reflective of sociodemographics, the health care system, and migration, varied by region of origin for Ontario's immigrant women.</p> <p>Methods</p> <p>Using a validated billing code algorithm, we determined the proportion of women who were not screened during the three-year period of 2006-2008 among 455 864 identified immigrant women living in Ontario's urban centres. We created eight identical multivariate Poisson models, stratified by eight regions of origin for immigrant women. In these models, we adjusted for various sociodemographic, health care-related and migration-related variables. We then used the resulting adjusted relative risks to calculate population-attributable fractions for each variable by region of origin.</p> <p>Results</p> <p>Region of origin was not a significant source of effect modification for lack of recent cervical cancer screening. Certain variables were significantly associated with lack of screening across all or nearly all world regions. These consisted of not being in the 35-49 year age group, residence in the lowest-income neighbourhoods, not being in a primary care patient enrolment model, a provider from the same region, and not having a female provider. For all women, the highest population-attributable risk was seen for not having a female provider, with values ranging from 16.8% [95% CI 14.6-19.1%] among women from the Middle East and North Africa to 27.4% [95% CI 26.2-28.6%] for women from East Asia and the Pacific.</p> <p>Conclusions</p> <p>To increase screening rates across immigrant groups, efforts should be made to ensure that women have access to a regular source of primary care, and ideally access to a female health professional. Efforts should also be made to increase the enrolment of immigrant women in new primary care patient enrolment models.</p

Effects of immunomodulatory drugs on TNF-α and IL-12 production by purified epidermal langerhans cells and peritoneal macrophages

<p>Abstract</p> <p>Background</p> <p>Langerhans cells constitute a special subset of immature dendritic cells localized in the epidermis that play a key role in the skin's immune response. The production of cytokines is a key event in both the initiation and the regulation of immune responses, and different drugs can be used to remove or modify their production by DC and, therefore, alter immune responses in a broad spectrum of diseases, mainly in human inflammatory and autoimmune diseases. In the present study, we examined the effects of prednisone, thalidomide, cyclosporine A, and amitriptyline, drugs used in a variety of clinical conditions, on the production of TNF-α, IL-10, and IL-12 by purified epidermal Langerhans cells and peritoneal macrophages in BALB/c mice.</p> <p>Findings</p> <p>All drugs inhibited TNF-α production by Langerhans cells after 36 hours of treatment at two different concentrations, while prednisone and thalidomide decreased IL-12 secretion significantly, amitriptyline caused a less pronounced reduction and cyclosporine A had no effect. Additionally, TNF-α and IL-12 production by macrophages decreased, but IL-10 levels were unchanged after all treatments.</p> <p>Conclusions</p> <p>Our results demonstrate that these drugs modulate the immune response by regulating pro-inflammatory cytokine production by purified epidermal Langerhans cells and peritoneal macrophages, indicating that these cells are important targets for immunosuppression in various clinical settings.</p

Immature and Maturation-Resistant Human Dendritic Cells Generated from Bone Marrow Require Two Stimulations to Induce T Cell Anergy In Vitro

Immature dendritic cells (DC) represent potential clinical tools for tolerogenic cellular immunotherapy in both transplantation and autoimmunity. A major drawback in vivo is their potential to mature during infections or inflammation, which would convert their tolerogenicity into immunogenicity. The generation of immature DC from human bone marrow (BM) by low doses of GM-CSF (lowGM) in the absence of IL-4 under GMP conditions create DC resistant to maturation, detected by surface marker expression and primary stimulation by allogeneic T cells. This resistence could not be observed for BM-derived DC generated with high doses of GM-CSF plus IL-4 (highGM/4), although both DC types induced primary allogeneic T cell anergy in vitro. The estabishment of the anergic state requires two subsequent stimulations by immature DC. Anergy induction was more profound with lowGM-DC due to their maturation resistance. Together, we show the generation of immature, maturation-resistant lowGM-DC for potential clinical use in transplant rejection and propose a two-step-model of T cell anergy induction by immature DC

The Hepatitis B Virus Ribonuclease H Is Sensitive to Inhibitors of the Human Immunodeficiency Virus Ribonuclease H and Integrase Enzymes

Nucleos(t)ide analog therapy blocks DNA synthesis by the hepatitis B virus (HBV) reverse transcriptase and can control the infection, but treatment is life-long and has high costs and unpredictable long-term side effects. The profound suppression of HBV by the nucleos(t)ide analogs and their ability to cure some patients indicates that they can push HBV to the brink of extinction. Consequently, more patients could be cured by suppressing HBV replication further using a new drug in combination with the nucleos(t)ide analogs. The HBV ribonuclease H (RNAseH) is a logical drug target because it is the second of only two viral enzymes that are essential for viral replication, but it has not been exploited, primarily because it is very difficult to produce active enzyme. To address this difficulty, we expressed HBV genotype D and H RNAseHs in E. coli and enriched the enzymes by nickel-affinity chromatography. HBV RNAseH activity in the enriched lysates was characterized in preparation for drug screening. Twenty-one candidate HBV RNAseH inhibitors were identified using chemical structure-activity analyses based on inhibitors of the HIV RNAseH and integrase. Twelve anti-RNAseH and anti-integrase compounds inhibited the HBV RNAseH at 10 μM, the best compounds had low micromolar IC50 values against the RNAseH, and one compound inhibited HBV replication in tissue culture at 10 μM. Recombinant HBV genotype D RNAseH was more sensitive to inhibition than genotype H. This study demonstrates that recombinant HBV RNAseH suitable for low-throughput antiviral drug screening has been produced. The high percentage of compounds developed against the HIV RNAseH and integrase that were active against the HBV RNAseH indicates that the extensive drug design efforts against these HIV enzymes can guide anti-HBV RNAseH drug discovery. Finally, differential inhibition of HBV genotype D and H RNAseHs indicates that viral genetic variability will be a factor during drug development. © 2013 Tavis et al

Tailored design of NKT-stimulatory glycolipids for polarization of immune responses

Natural killer T (NKT) cell is a distinct population of T lymphocytes that can rapidly release massive amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor with glycolipids presented by CD1d. The secreted cytokines can promote cell-mediated immunity to kill tumor cells and intracellular pathogens, or suppress autoreactive immune cells in autoimmune diseases. Thus, NKT cell is an attractive target for developing new therapeutics to manipulate immune system. The best-known glycolipid to activate NKT cells is α-galactosylceramide (α-GalCer), which has been used as a prototype for designing new NKT stimulatory glycolipids. Many analogues have been generated by modification of the galactosyl moiety, the acyl chain or the phytosphingosine chain of α-GalCer. Some of the analogues showed greater abilities than α-GalCer in polarizing immune responses toward Th1 or Th2 dominance. Among them, several analogues containing phenyl groups in the lipid tails were more potent in inducing Th1-skewed cytokines and exhibited greater anticancer efficacy than α-GalCer. Analyses of the correlation between structure and activity of various α-GalCer analogues on the activation of iNKT cell revealed that CD1d–glycolipid complexes interacted with the same population of iNKT cell expressing similar T-cell receptor Vβ as α-GalCer. On the other hand, those phenyl glycolipids with propensity for Th1 dominant responses showed greater binding avidity and stability than α-GalCer for iNKT T-cell receptor when complexed with CD1d. Thus, it is the avidity and stability of the ternary complexes of CD1d-glycolipid-iNKT TCR that dictate the polarity and potency of immune responses. These findings provide a key to the rationale design of immune modulating glycolipids with desirable Th1/Th2 polarity for clinical application. In addition, elucidation of α-GalCer-induced anergy, liver damage and accumulation of myeloid derived suppressor cells has offered explanation for its lacklustre anti-cancer activities in clinical trials. On other hand, the lack of such drawbacks in glycolipid analogues containing phenyl groups in the lipid tails of α-GalCer coupled with the greater binding avidity and stability of CD1d-glycolipid complex for iNKT T-cell receptor, account for their superior anti-cancer efficacy in tumor bearing mice. Further clinical development of these phenyl glycolipids is warranted

A Molecular Signature of Proteinuria in Glomerulonephritis

Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 “albumin-regulated genes” differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n = 25) could be distinguished from those of control subjects (n = 6) based solely upon the expression of these 231 “albumin-regulated genes.” The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that all forms of primary glomerulonephritis (n = 33) can be distinguished from controls (n = 21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis