CSF from Parkinson disease patients differentially affects cultured microglia and astrocytes.

BACKGROUND: Excessive and abnormal accumulation of alpha-synuclein (α-synuclein) is a factor contributing to pathogenic cell death in Parkinson's disease. The purpose of this study, based on earlier observations of Parkinson's disease cerebrospinal fluid (PD-CSF) initiated cell death, was to determine the effects of CSF from PD patients on the functionally different microglia and astrocyte glial cell lines. Microglia cells from human glioblastoma and astrocytes from fetal brain tissue were cultured, grown to confluence, treated with fixed concentrations of PD-CSF, non-PD disease control CSF, or control no-CSF medium, then photographed and fluorescently probed for α-synuclein content by deconvolution fluorescence microscopy. Outcome measures included manually counted cell growth patterns from day 1-8; α-synuclein density and distribution by antibody tagged 3D model stacked deconvoluted fluorescent imaging. RESULTS: After PD-CSF treatment, microglia growth was reduced extensively, and a non-confluent pattern with morphological changes developed, that was not evident in disease control CSF and no-CSF treated cultures. Astrocyte growth rates were similarly reduced by exposure to PD-CSF, but morphological changes were not consistently noted. PD-CSF treated microglia showed a significant increase in α-synuclein content by day 4 compared to other treatments (p ≤ 0.02). In microglia only, α-synuclein aggregated and redistributed to peri-nuclear locations. CONCLUSIONS: Cultured microglia and astrocytes are differentially affected by PD-CSF exposure compared to non-PD-CSF controls. PD-CSF dramatically impacts microglia cell growth, morphology, and α-synuclein deposition compared to astrocytes, supporting the hypothesis of cell specific susceptibility to PD-CSF toxicity.

Shigellosis in Hidalgo County, Texas 2005--2009: A descriptive study

Shigellosis is a communicable disease harbored primarily by humans. The low infective dose, no vaccine availability, and mild or asymptomatic nature of disease has prevented eradication of Shigella in the United States. In addition, the lack of water and sewage infrastructures which normally contribute to the spread of disease in developing countries, for the most part, is a non-issue in the U.S. making surveillance and risk factor identification important prevention and control measures utilized to reduce the incidence rates of Shigellosis.^ The purpose of this study was to describe the Shigellosis disease burden among the Hidalgo County, Texas population during the 2005-2009 study period and compare these findings with national data available. The potential identification and publication of a health disparity in the form of increased Shigellosis rates among Hidalgo County residents when compared to national rates, especially age-specific rates, are intended to generate public health attention and public health action that will address this issue.^ There were 1,007 confirmed Shigellosis cases reported in Hidalgo County, Texas. An overwhelming majority (79%) of the Shigellosis cases during this time frame occurred in children less than ten years of age. Over the age of 10 through the age of 39, females constituted the majority of cases. Age-specific rates for children four years of age and younger were compared to national rates. The rates for Hidalgo County were higher at 9.2 and 1.8 cases for every one case reported nationally in 2005 and 2006, respectively. The total crude rates of Shigellosis were also higher than the rates available from the Foodborne Diseases Active Surveillance Network (FoodNet) of CDC’s Emerging Infections Program from 2005-2009. As a result, compared to the FoodNet surveillance rates, Hidalgo County experienced above average rates of Shigellosis throughout the study period. The majority of cases were identified in young children under the age of ten.^ The information gathered in this analysis could be used to implement and monitor infection control measures such as hand washing education at facilities that tend to the groups identified at higher risk of infection. In addition, the higher burden of disease found in Hidalgo County requires further study to determine if there are factors associated with an increased risk of Shigellosis in this community and other border communities along the U.S.-Mexico border exist.^

CLINICAL TRIAL ENROLLMENT IN A MULTIDISCIPLINARY PROSTATE CANCER

Purpose: Clinical oncology trials are hampered by low accrual rates. Less than 5% of adult cancer patients are treated on a clinical trial. We aimed to evaluate clinical trial enrollment in our Multidisciplinary Prostate Cancer Clinic and to assess if a clinical trial initiative, introduced in 2006, increased our trial enrollment.Methods: Prostate cancer patients with non-metastatic disease who were seen in the clinic from 2004 to 2008 were included in the analysis. Men were categorized by whether they were seen before or after the clinical trial enrollment initiative started in 2006. The initiative included posting trial details in the clinic, educating patients about appropriate clinical trial options during the treatment recommendation discussion, and providing patients with documentation of trials offered to them. Univariate and multivariate (MVA) logistic regression analysis evaluated the impact of patient characteristics and the clinical trial initiative on clinical trial enrollment.Results: The majority of the 1,370 men were white (83%), and lived within the surrounding counties or state (69.4%). Median age was 64.2 years. Seventy-three point five percent enrolled in at least one trial and 28.5% enrolled in more than one trial. Sixty-seven percent enrolled in laboratory studies, 18% quality of life studies, 13% novel studies, and 3.7% procedural studies. On MVA, men seen in later years (p < 0.0001) were more likely to enroll in trials. The proportion of men enrolling increased from 38.9% to 84.3% (p<0.0001) after the clinical trial initiative. On MVA, older men (p < 0.0001) were less likely to enroll in clinical trials. There was a trend toward men in the high-risk group being more likely to participate in clinical trials (p = 0.056). There was a second trend for men of Hispanic, Asian, Native American and Indian decent being less likely to participate in clinical trials (p = 0.054).Conclusion: Clinical trial enrollment in the multidisciplinary clinic increased after introduction of a clinical trial initiative. Older men were less likely to enroll in trials. We speculate we achieved high enrollment rates because 1) specific trials are discussed at time of treatment recommendations, 2) we provide a letter documenting offered trials and 3) we introduce patients to the research team at the same clinic visit if they are interested in trial participation.

Hormone therapy and physical activity as predictors of lung cancer risk and survival: The California Teachers Study

Cigarette smoking is responsible for the majority of lung cancer cases worldwide; however, a proportion of never smokers still develop lung cancer over their lifetime, prompting investigation into additional factors that may modify lung cancer incidence, as well as mortality. Although hormone therapy (HT), physical activity (PA), and lung cancer have been previously examined, the associations remain unclear. This study investigated exposure to HT and PA that may modulate underlying mechanisms of lung cancer etiology and progression among women by using existing, de-identified data from the California Teachers Study (CTS).^ The CTS cohort, established in 1995–1996, has 133,479 active and retired female teachers and administrators, recruited through the California State Teachers Retirement System, and followed annually for cancer diagnosis, death, and change of address. Each woman enrolled in the CTS returned a questionnaire covering a wide variety of issues related to cancer risk and women's health, including recent and past HT use and physical activity, as well as active and environmental cigarette smoke exposure. Complete data to assess the associations between HT and lung cancer risk and survival were available for 60,592 postmenopausal women. Between 1995 and 2007, 727 of these women were diagnosed with invasive lung cancer; 441 of these died. Complete data to assess the associations between PA and lung cancer risk and survival were available for 118,513 women. Between 1995 and 2007, 853 of these women were diagnosed with invasive lung cancer; 516 of these died.^ After careful adjustment for smoking habits and other potential confounders, no measure of HT use was associated with lung cancer risk; however, any HT use (vs. no use) was associated with a decrease in lung-cancer-specific mortality. Specifically, among women who only used estrogen (E-only), decreases in lung cancer mortality were seen for recent use, but not for former use; no association was observed for estrogen plus progestin (E+P). Furthermore, among former users of HT, a statistically significant decrease in lung cancer mortality was observed for E-only use within 5 years prior to baseline, but not for E-only use >5 years prior to baseline. Neither long-term recreational PA nor recent recreational PA alone were associated with lung cancer risk; however, among women with a BMI<25 and ever smokers, high long-term moderate+strenuous PA was associated with a decrease in lung cancer risk. Women with non-local disease showed a decrease in lung cancer mortality associated with increasing duration of strenuous long-term activity, and 1.50-3.00 h/wk/y of recent moderate or recent strenuous PA. Long-term moderate PA was associated with decreased lung cancer mortality in never smokers, whereas recent moderate PA was associated with increased lung cancer mortality in current smokers. ^ Placing our findings in the context of the current literature, HT does not appear to be associated with lung cancer risk and previous studies reporting a protective effect of HT use on lung cancer risk may be subject to residual confounding by smoking. Looking at our findings regarding PA overall, the evidence still remains inconclusive regarding whether or not physical activity influence lung cancer risk or mortality. Our results suggest that recreational PA may associated with decreased lung cancer risk among women with BMI<25 and ever smoking-women; however, residual confounding by smoking should be strongly considered. To our knowledge, this is the first study to investigate lifetime recreational PA and lung cancer mortality among women. Our results contribute to the growing body of knowledge regarding non-smoking-related risk factors for lung cancer incidence and mortality among women. Given the potential clinical and interventional significance, further study and validation of these findings is warranted.^

Minority preferences and disease types for non-emergent emergency department usage in a CHIP population

Background. Of the over five million annual pediatric visits to U.S. emergency departments, one-third to one-half are for non-emergent conditions. Minorities are more likely to utilize the emergency department (ED) for non-emergent conditions. Very little research has analyzed the role of illness type, perceived need, or family preferences in explaining this disparity. ^ Objectives. This study examined racial-ethnic differences in preferences for care among non-emergent users of the ED. ^ Research design. A random selection of pediatric non-emergent ED users within a single CHIP managed care plan were surveyed regarding attitudes and health care preferences. Preferences for ED utilization were analyzed by racial-ethnic category, controlling for illness type, child and guardian age, education level, language, and perceived need. ^ Results. A total of 250 families were surveyed. Most respondents reported having a regular doctor, satisfaction with their physician, and ready access to their physician. Fifteen percent of White, 39% of Hispanic, and 38% of Black families reported they preferred the emergency department for ill care. In multivariate analysis, Whites families were significantly less likely to prefer the emergency department for ill visits (odds ratio, 0.12; 95% confidence interval 0.03-0.55) compared to Blacks and Hispanics. ^ Conclusions. Racial-ethnic disparities in non-emergent ED utilization may be partially explained by different preferences for care. ^ Key words: children, emergency department, preferences for care, disparities ^

Anti-glomerular basement membrane glomerulonephritis: Characterization of an epitope, antibody response, and the potential role of IL-4Ralpha in disease progression

Anti-Glomerular Basement Membrane Glomerulonephritis (anti-GBM GM) is one of the earliest described autoimmune disorders. Patients present with proteinuria, anti-GBM antibodies, and renal failure. Studies have implicated a T Helper 1 (TH1) response in disease induction and a T Helper 2 (TH2) response for disease progression. A 13 amino acid long peptide sequence spanning residues 28 through 40 [pCol(28–40)] of the Collagen IV α3 non-collagen domain (Col IV α3 NCD) is immunogenic and induces anti-GBM GN. In order to fully understand disease initiation, this peptide was further characterized. Peptides were created containing one amino acid substitution for the entire length of pCol(28–40) and induction of anti-GBM GN was monitored. When residues 31, 33, or 34 contained the substitution, anti-GBM GN was unable to be induced. Thus, residues 31, 33, and 34 of pCol(28–40) are required for induction of anti-GBM. Glomerular injury is observed as early as 14 days post anti-GBM GN induction. However, the presence of anti-GBM antibodies is not observed until 20 days post immunization. An enlarged lymph node adjacent to the diseased kidney exhibits B cell activation after renal injury and produces antibodies toward GBM. Thus, anti-GBM antibodies are a consequence of the initial renal injury. Differences between disease susceptible and disease resistant rat strains exist in the expression of IL-4Rα, a major player in the TH2 response. IL-4Rα signaling is regulated by soluble IL-4Rα (sIL-4Rα). Low expression levels of sIL-4Rα result in the stabilization of IL-4 binding, while elevated expression sequesters IL-4. Quantitative PCR experiments noted low siL-4Rα expression levels in disease susceptible rats. Induction of an immune response toward sIL-4Rα in this strain was responsible for delayed disease progression in 15 out of the 17 experimental animals. Antibody transfer and in vivo biological activity experiments confirmed that delayed disease development was due to anti-sIL-4Rα antibodies. Together these experiments indicate that a T-cell epitope is required for activation of a TH1 autoimmune response and anti-GBM antibodies are a consequence of renal injury. More importantly, a role for IL-4Rα signaling is implicated in the progression of anti-GBM GN. ^

The relationship between supermarket nutrient movements and the mortality rates from fat-associated and non-fat-associated cardiovascular disease: Development of an ecologic method for determining community food patterns

Supermarket nutrient movement, a community food consumption measure, aggregated 1,023 high-fat foods, representing 100% of visible fats and approximately 44% of hidden fats in the food supply (FAO, 1980). Fatty acid and cholesterol content of foods shipped from the warehouse to 47 supermarkets located in the Houston area were calculated over a 6 month period. These stores were located in census tracts with over 50% of a given ethnicity: Hispanic, black non-Hispanic, or white non-Hispanic. Categorizing the supermarket census tracts by predominant ethnicity, significant differences were found by ANOVA in the proportion of specific fatty acids and cholesterol content of the foods examined. Using ecological regression, ethnicity, income, and median age predicted supermarket lipid movements while residential stability did not. No associations were found between lipid movements and cardiovascular disease mortality, making further validation necessary for epidemiological application of this method. However, it has been shown to be a non-reactive and cost-effective method appropriate for tracking target foods in populations of groups, and for assessing the impact of mass media nutrition education, legislation, and fortification on community food and nutrient purchase patterns. ^