Leishmaniasis in cat shelters: A serological,molecular and entomological study

An epidemiological Leishmania spp. and entomological Phlebotomine sandflies survey was performed in cat shelters at leishmaniasis endemic area of Brazil. Blood and conjunctival swab (CS) samples were collected from 94 cats in two animal protection shelters. These samples were subjected to serological tests using the indirect immunofluorescence antibody test (IFAT) and indirect enzyme‐linked immunosorbent assay (ELISA) and to molecular test by polymerase chain reaction (PCR). In addition, a Phlebotomine sandflies survey was performed in the same shelters. The analyses revealed a positivity of 31.91% (30/94) through ELISA and 29.79% (28/94) through IFAT. The two serological tests showed a positive association with perfect agreement (k = 0.925). None of the cats were positive by Leishmania spp. DNA. One Lutzomyia (Lutzomyia) longipalpis male was found in one of the cat shelters. The results and the implications of our findings are discussed below.     

Centrosome amplification drives chromosomal instability in breast tumor development

Earlier studies of invasive breast tumors have shown that 60-80% are aneuploid and approximately 80% exhibit amplified centrosomes. In this study, we investigated the relationship of centrosome amplification with aneuploidy, chromosomal instability, p53 mutation, and loss of differentiation in human breast tumors. Twenty invasive breast tumors and seven normal breast tissues were analyzed by fluorescence in situ hybridization with centromeric probes to chromosomes 3, 7, and 17. We analyzed these tumors for both aneuploidy and unstable karyotypes as determined by chromosomal instability. The results were then tested for correlation with three measures of centrosome amplification: centrosome size, centrosome number, and centrosome microtubule nucleation capacity. Centrosome size and centrosome number both showed a positive, significant, linear correlation with aneuploidy and chromosomal instability. Microtubule nucleation capacity showed no such correlation, but did correlate significantly with loss of tissue differentiation. Centrosome amplification was detected in in situ ductal carcinomas, suggesting that centrosome amplification is an early event in these lesions. Centrosome amplification and chromosomal instability occurred independently of p53 mutation, whereas p53 mutation was associated with a significant increase in centrosome microtubule nucleation capacity. Together, these results demonstrate that independent aspects of centrosome amplification correlate with chromosomal instability and loss of tissue differentiation and may be involved in tumor development and progression. These results further suggest that aspects of centrosome amplification may have clinical diagnostic and/or prognostic value and that the centrosome may be a potential target for cancer therapy.     

Loss of cooperative function of transforming growth factor-beta signaling proteins, smad3 with embryonic liver fodrin, a beta-spectrin, in primary biliary cirrhosis.

Modulation of fibrogenesis, epithelial, and mesenchymal cell fates are prominent effects of transforming growth factor-beta (TGF-beta) signaling by Smad proteins. We have previously shown that Smad2 and Smad3 insufficiency leads to a loss of bile ducts. In addition, Smad3/4 activity is mediated by embryonic liver fodrin (ELF), a beta-Spectrin. In mouse elf(-/-) mutants and in liver explant cultures, loss of ELF function results in T lymphocytic proliferation and absent intrahepatic bile ducts. A similar phenotype is seen in a number of cholestatic diseases with progressive loss of intrahepatic bile ducts and fibrosis. However, the expression patterns of Smads or role of ELF in cholestatic and fibrotic liver diseases are not yet known. METHODS/RESULTS: We investigated the role of ELF in primary biliary cirrhosis (PBC), autoimmune hepatitis C, chronic viral hepatitis and in livers from mice deficient in Smad2/Smad3. We generated elf(+/-) mutant mice and analyzed for chronic liver disease and hepatocellular cancer (HCC) from 6 to 12 months. Perturbations in ELF expression were consistently seen only in PBC tissues. ELF expression was similarly aberrant in tissues from Smad2(+/-)/Smad3(+/-) mutant mice. Further studies indicated that ELF mislocalization is correlated with aberrant localization of Smad3 in some PBC tissues. Thirteen of 17 elf(+/-) mutant mice developed steatosis, fibrosis, hepatic dysplasia, with HCC in two mice. CONCLUSIONS: These results suggest that a compromised cytoarchitecture and polarized trafficking of TGF-beta signaling molecules, ELF and Smad3 are involved in the pathogenesis of PBC as well as HCC.     

Autoimmune cytopenias in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is frequently complicated by secondary autoimmune cytopenias (AIC) represented by autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia, and autoimmune granulocytopenia. The distinction of immune cytopenias from cytopenias due to bone marrow infiltration, usually associated with a worse outcome and often requiring a different treatment, is mandatory. AIHA and ITP are more frequently found in patients with unfavorable biological risk factors for CLL. AIC secondary to CLL respond less favorably to standard treatments than their primary forms, and treating the underlying CLL with chemotherapy or monoclonal antibodies may ultimately be necessary. Am. J. Hematol. 89:1055–1062, 2014. © 2014 Wiley Periodicals, Inc.     

Educational Disparities in the Burden of Disability: Contributions of Disease Prevalence and Disabling Impact

Objectives. We assessed the contributions of the prevalence and disabling impact of specific diseases to educational disparities in the prevalence of disability.Methods. We examined a large representative survey of the Dutch population, the Dutch Permanent Survey of Living Conditions (2001–2007; n = 24 883; ages 40–97 years). We attributed the prevalence of disability to chronic diseases by using their empirical associations and assuming independent competing causes of disability. We estimated contributions of prevalence and the disabling impact of diseases to disparities in disability using counterfactuals.Results. We found that the prevalence of disability in individuals with only an elementary education was 19 to 20 percentage points higher than that in individuals with tertiary education. Sixty-five percent of this difference could be attributed to specific chronic diseases, but more so to their disabling impact (49%–51%) than to their prevalence (20%–29%). Back pain, neck or arm conditions, and peripheral vascular disease contributed most to the disparity in men, and arthritis, back pain, and chronic nonspecific lung disease contributed most to the disparity in women.Conclusions. Educational disparities in the burden of disability were primarily caused by high disabling impacts of chronic diseases among low educated groups. Tackling disparities might require more effective treatment or rehabilitation of disability in lower socioeconomic groups.Worldwide, health is strongly patterned along socioeconomic lines.1,2 Those with the lowest income or with the lowest level of education are consistently less healthy on numerous health indicators.1–3 For example, a recent study using data from the World Health Survey showed significant and substantial pro-rich inequality in the prevalence of disability in 43 of 49 countries worldwide.3 The disparities, also in disability, have not declined, but appear to have a strongly persistent nature.4–6 Reducing health disparities is a top priority of health policy agendas, and there is an urgent need to develop interventions that effectively reduce socioeconomic disparities in health.7 This requires that we know which diseases and determinants contribute most to health disparities, but studies assessing contributions of specific diseases to disparities in fatal and nonfatal health outcomes are limited in number.With respect to fatal outcomes, several studies show that various diseases contribute to socioeconomic disparities in total mortality, but that a few conditions contribute most.1,8–13 For example, Huisman et al.8 found that among European men, cardiovascular diseases accounted for 39% of the difference between low and high educational groups in total mortality, cancer accounted for 24%, other diseases accounted for 32%, and external causes accounted for 5%. Among women, contributions were 60%, 11%, 30%, and 0%, respectively.8 A relative stagnation of cardiovascular mortality declines among low socioeconomic groups has contributed to the persistence and even widening of disparities in total mortality over the past few decades.5With respect to nonfatal health outcomes, substantial disparities exist in terms of the occurrence of many chronic diseases and in generic health outcomes, such as disability.3,14 Only a handful of studies has investigated which diseases contribute most to the socioeconomic disparity in the burden of disability. In a study by Sainio et al.,15 diabetes contributed most to educational disparities in stair climbing limitations among men, and osteoarthritis of the knee and angina pectoris contributed most among women. In a study by Koster et al.,16 knee pain contributed most to an excess hazard for mobility limitations among low educated persons. In another study, Nusselder et al.17 found that in the Belgian population, back complaints and arthritis contributed most to educational disparities in years lived with functional mobility limitations among men, and that arthritis and chronic nonspecific lung disease contributed most among women.The latter study clearly showed that substantial differences exist in the prevalence of and in the disabling impact of chronic diseases, and suggested that both contribute to the total disparity in disability. Because these 2 aspects may require an entirely different intervention approach, knowing their relative contribution to disparities in disability is crucial for policy development. To our knowledge, no study has investigated to what extent the total inequality in the burden of disability is explained by differences in the prevalence of diseases and by differences in the disabling impact. Our aim in this study was to assess contributions of differences in the prevalence and the disabling impact of specific diseases to educational disparities in the prevalence of disability.     

Prospectively measured 10-year changes in health-related quality of life and comparison with cross-sectional estimates in a population-based cohort of adult women and men

Purpose

To prospectively assess changes in health-related quality of life (HRQOL) over 10 years, by age and sex, and to compare measured within-person change to estimates of change based on cross-sectional data.

Methods

Participants in the Canadian Multicentre Osteoporosis Study completed the 36-item short form (SF-36) in 1995/1997 and 2005/2007. Mean within-person changes for domain and summary components were calculated for men and women separately, stratified by 10-year age groups. Projected changes based on published age- and sex-stratified cross-sectional data were also calculated. Mean differences between the two methods were then estimated, along with the 95 % credible intervals of the differences.

Results

Data were available for 5,569/9,423 (59.1 %) of the original cohort. Prospectively collected 10-year changes suggested that the four physically oriented domains declined in all but the youngest group of men and women, with declines in the elderly men exceeding 25 points. The four mentally oriented domains tended to improve over time, only showing substantial declines in vitality and role emotional in older women, and all four domains in older men. Cross-sectional estimates identified a similar pattern of change but with a smaller magnitude, particularly in men. Correspondence between the two methods was generally high.

Conclusions

Changes in HRQOL may be minimal over much of the life span, but physically oriented HRQOL can decline substantially after middle age. Although clinically relevant declines were more evident in prospectively collected data, differences in 10-year age increments of cross-sectional data may be a reasonable proxy for longitudinal changes, at least in those under 65 years of age. Results provide additional insight into the natural progression of HRQOL in the general population.