Racial and Ethnic Differences in Cardiovascular Disease Risk Factors in U.S. Older Women: Findings from Behavioral Risk Factor Surveillance Survey, 2003 & 2004

The purpose of this study was to examine racial and ethnic variations in the modifiable CVD risk factors in older women (65 years and older). The study data was drawn from the merged 2003 and 2004 national Behavioral Risk Factor Surveillance Survey (BRFSS). Multinomial regression analyses for indicator outcome and multiple logistic regression analyses for binary outcomes were performed to determine the relationship between each of the six dependent variable and the independent variables. Compared to older white women, older black women had significantly higher odds of hypertension, diabetes and obesity. No significant association was found between Hispanics and hypertension. However Hispanics were found to be more likely to have diabetes and no leisure-time physical activity compared to whites. Hispanics were also found to have lower odds of smoking compared to whites. American Indian and Alaskan Native (AIAN) s were found to have significantly higher odds of diabetes and obesity compared to whites. No significant association between AIANs and smoking was found. Overall, there are striking racial and ethnic differences in the CVD risk factors among older U.S women after controlling for socio-economic status. It is evident from these findings that in designing interventions to reduce cardiovascular risks for elderly women, clearly “one size does not fit all.” These findings highlight the need for development and implementation of appropriate public health programs aimed at these various target communities

Differences in risk factors for children with special health care needs (CSHCN) receiving needed specialty care by socioeconomic status

<p>Abstract</p> <p>Background</p> <p>The purpose of this study is to identify factors affecting CSHCN's receiving needed specialty care among different socioeconomic levels. Previous literature has shown that Socioeconomic Status (SES) is a significant factor in CHSHCN receiving access to healthcare. Other literature has shown that factors of insurance, family size, race/ethnicity and sex also have effects on these children's receipt of care. However, this literature does not address whether other factors such as maternal education, geographic location, age, insurance type, severity of condition, or race/ethnicity have different effects on receiving needed specialty care for children in each SES level.</p> <p>Methods</p> <p>Data were obtained from the National Survey of Children with Special Health Care Needs, 2000–2002. The study analyzed the survey which studies whether CHSCN who needed specialty care received it. The analysis included demographic characteristics, geographical location of household, severity of condition, and social factors. Multiple logistic regression models were constructed for SES levels defined by federal poverty level: < 199%; 200–299%; ≥ 300%.</p> <p>Results</p> <p>For the poorest children (,199% FPL) being uninsured had a strong negative effect on receiving all needed specialty care. Being Hispanic was a protective factor. Having more than one adult in the household had a positive impact on receipt of needed specialty care but a larger number of children in the family had a negative impact. For the middle income group of children (200–299% of FPL severity of condition had a strong negative association with receipt of needed specialty care.</p> <p>Children in highest income group (> 300% FPL) were positively impacted by living in the Midwest and were negatively impacted by the mother having only some college compared to a four-year degree.</p> <p>Conclusion</p> <p>Factors affecting CSHCN receiving all needed specialty care differed among socioeconomic groups. These differences should be addressed in policy and practice. Future research should explore the CSHCN population by income groups to better serve this population</p

Impaired Chromatin Remodelling at STAT1-Regulated Promoters Leads to Global Unresponsiveness of Toxoplasma gondii-Infected Macrophages to IFN-γ

Intracellular pathogens including the apicomplexan and opportunistic parasite Toxoplasma gondii profoundly modify their host cells in order to establish infection. We have shown previously that intracellular T. gondii inhibit up-regulation of regulatory and effector functions in murine macrophages (MΦ) stimulated with interferon (IFN)-γ, which is the cytokine crucial for controlling the parasites' replication. Using genome-wide transcriptome analysis we show herein that infection with T. gondii leads to global unresponsiveness of murine macrophages to IFN-γ. More than 61% and 89% of the transcripts, which were induced or repressed by IFN-γ in non-infected MΦ, respectively, were not altered after stimulation of T. gondii-infected cells with IFN-γ. These genes are involved in a variety of biological processes, which are mostly but not exclusively related to immune responses. Analyses of the underlying mechanisms revealed that IFN-γ-triggered nuclear translocation of STAT1 still occurred in Toxoplasma-infected MΦ. However, STAT1 bound aberrantly to oligonucleotides containing the IFN-γ-responsive gamma-activated site (GAS) consensus sequence. Conversely, IFN-γ did not induce formation of active GAS-STAT1 complexes in nuclear extracts from infected MΦ. Mass spectrometry of protein complexes bound to GAS oligonucleotides showed that T. gondii-infected MΦ are unable to recruit non-muscle actin to IFN-γ-responsive DNA sequences, which appeared to be independent of stimulation with IFN-γ and of STAT1 binding. IFN-γ-induced recruitment of BRG-1 and acetylation of core histones at the IFN-γ-regulated CIITA promoter IV, but not β-actin was diminished by >90% in Toxoplasma-infected MΦ as compared to non-infected control cells. Remarkably, treatment with histone deacetylase inhibitors restored the ability of infected macrophages to express the IFN-γ regulated genes H2-A/E and CIITA. Taken together, these results indicate that Toxoplasma-infected MΦ are unable to respond to IFN-γ due to disturbed chromatin remodelling, but can be rescued using histone deacetylase inhibitors

Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages

Macrophages play an essential role in the early immune response against Toxoplasma and are the cell type preferentially infected by the parasite in vivo. Interferon gamma (IFNγ) elicits a variety of anti-Toxoplasma activities in macrophages. Using a genome-wide CRISPR screen we identify 353 Toxoplasma genes that determine parasite fitness in naїve or IFNγ-activated murine macrophages, seven of which are further confirmed. We show that one of these genes encodes dense granule protein GRA45, which has a chaperone-like domain, is critical for correct localization of GRAs into the PVM and secretion of GRA effectors into the host cytoplasm. Parasites lacking GRA45 are more susceptible to IFNγ-mediated growth inhibition and have reduced virulence in mice. Together, we identify and characterize an important chaperone-like GRA in Toxoplasma and provide a resource for the community to further explore the function of Toxoplasma genes that determine fitness in IFNγ-activated macrophages

Using cost and health impacts to prioritize the targeted testing of tuberculosis in the United States

Purpose: Evaluation improves efficiency and effectiveness. Current U.S. tuberculosis (TB) control policies emphasize the treatment of latent TB infection (LTBI). However, this policy, if not targeted, may be inefficient. We determined the efficiency of a state-law mandated TB screening program and a non state-law mandated one in terms of cost, morbidity, treatment, and disease averted. Methods: We evaluated two publicly funded metropolitan TB prevention and control programs through retrospective analyses and modeling. Main outcomes measured were TB incidence and prevalence, TB cases averted, and cost. Results: A non state-law mandated TB program for homeless persons in Tarrant County screened 4.5 persons to identify one with LTBI and 82 persons to identify one with TB. A state-law mandated TB program for jail inmates screened 109 persons to identify one with LTBI and 3274 persons to identify one with TB. The number of patients with LTBI treated to prevent one TB case was 12.1 and 15.3 for the homeless and jail inmate TB programs, respectively. Treatment of LTBI by the homeless and jail inmate TB screening programs will avert 11.9 and 7.9 TB cases at a cost of $14,350 and$34,761 per TB case, respectively. Conclusions: Mandated TB screening programs should be risk-based, not population-based. Non mandated targeted testing for TB in congregate settings for the homeless was more efficient than state-law mandated targeted testing for TB among jailed inmates

AMPA GluA1-flip targeted oligonucleotide therapy reduces neonatal seizures and hyperexcitability

<div><p>Glutamate-activated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA-Rs) mediate the majority of excitatory neurotransmission in brain and thus are major drug targets for diseases associated with hyperexcitability or neurotoxicity. Due to the critical nature of AMPA-Rs in normal brain function, typical AMPA-R antagonists have deleterious effects on cognition and motor function, highlighting the need for more precise modulators. A dramatic increase in the flip isoform of alternatively spliced AMPA-R GluA1 subunits occurs post-seizure in humans and animal models. GluA1-flip produces higher gain AMPA channels than GluA1-flop, increasing network excitability and seizure susceptibility. Splice modulating oligonucleotides (SMOs) bind to pre-mRNA to influence alternative splicing, a strategy that can be exploited to develop more selective drugs across therapeutic areas. We developed a novel SMO, GR1, which potently and specifically decreased GluA1-flip expression throughout the brain of neonatal mice lasting at least 60 days after single intracerebroventricular injection. GR1 treatment reduced AMPA-R mediated excitatory postsynaptic currents at hippocampal CA1 synapses, without affecting long-term potentiation or long-term depression, cellular models of memory, or impairing GluA1-dependent cognition or motor function in mice. Importantly, GR1 demonstrated anti-seizure properties and reduced post-seizure hyperexcitability in neonatal mice, highlighting its drug candidate potential for treating epilepsies and other neurological diseases involving network hyperexcitability.</p></div

A single ICV injection of GR1 provided a long-lasting reduction in GluA1-flip expression without adverse effects on cognition.

<p>Mice were a given ICV injection of GR1 (4 μg) at P10, <b>(a)</b> Real-time PCR showed GR1 reduced GluA1-flip in the cortex and hippocampus at all time-points from 2–60 d after administration (n = 4–5; p < 0.001). <b>(b)</b> GluA1-flop expression levels, measured in same samples as in panel <b>a</b>, were only marginally different between the GR1-treated and saline-treated controls. <b>(c)</b> GR1-treated mice did not show impairment in Y maze performance when tested at P30, compared to saline-treated controls (p > 0.05; n = 8–9). <b>(d)</b> In the object recognition paradigm, GR1-injected mice showed similar preferences for exploring novel objects as saline-injected controls (p > 0.05 between groups; same cohort of mice as in panel <b>c</b>). GluA1-flip expression was analyzed by one-sample Student’s t-test with bonferoni correction, novel object preference by unpaired two-sample two-tailed t-tests, and Y-maze performance by Fischer’s exact test.</p