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Weight gain and other metabolic sequelae of antipsychotic medications can lead to medication non-adherence, reduced quality of life, increased costs, and premature mortality. Of the approaches to address this, behavioral interventions are less invasive, cost less, and can result in sustained long-term benefits. We investigated behavioral weight management interventions for veterans with mental illness across four medical centers within the Veterans Affairs (VA) Healthcare System. We conducted a 12-month, multi-site extension of our previous randomized, controlled study, comparing treatment and control groups. Veterans (and some non-veteran women) diagnosed with mental illness, overweight (defined as having a BMI over 25), and required ongoing antipsychotic therapy. One group received “Lifestyle Balance” (LB; modified from the Diabetes Prevention Program) consisting of classes and individual nutritional counseling with a dietitian. A second group received less intensive “Usual Care” (UC) consisting of weight monitoring and provision of self-help. Participants completed anthropometric and nutrition assessments weekly for 8 weeks, then monthly. Psychiatric, behavioral, and physical assessments were conducted at baseline and months 2, 6, and 12. Metabolic and lipid laboratory tests were performed quarterly. Participants in both groups lost weight. LB participants had a greater decrease in average waist circumference [F(1,1244) = 11.9, p

Background: Second-generation antipsychotic medications have proven effective for individuals with serious mental illness (SMI) but may cause weight gain and other metabolic sequelae. Investigators designed and assessed a 12-month behavioral intervention for overweight/obese patients with SMI called “Lifestyle Balance” (LB), based on the Diabetes Prevention Program (DPP), which was tested at 4 VA sites.

Background: The delivery of mental health care is shifting to one that is patient-centered and recovery-oriented, with the goal of increasing quality of life. These pilot studies test an adjunctive, holistic, behavioral approach to treating serious mental illness (SMI) and medication-associated weight gain; investigators hypothesized that engagement in a greater number of therapeutic lifestyle changes (TLCs) leads to improvement in quality of life, reduction of psychiatric symptoms, and weight loss.

The Genuine Progress Indicator (GPI) was designed to reveal the trade-offs between costs and benefits of economic growth. Although originally estimated and contrasted with Gross Domestic Product (GDP) at national scales, an interest in a state-level adoption has developed in the United States to inform and guide policy. As GPI scholarship and a community of practice has developed, questions have arisen about the quality and legitimacy of the GPI. To investigate, we apply a composite indicator analysis developed by the Organization for Economic Co-operation and Development (OECD) to fifty US state GPI estimates using a consistent method. We focus on a multi-variate analysis of the structure of the composite, sensitivity to weighting and aggregation assumptions, and the statistical relationship with other well-being indicators. Results are heavily influenced by a small number of components, point to a number of unintended policy outcomes, and have mixed relationships with allied indicators. The study suggests steps towards shared GPI governance among practitioners and researchers, consideration of data parsimony and potential double-counting, and data selection criteria to help fill gaps, prioritize needs, and better articulate the purpose and meaning of GPI.

Latent infection from Toxoplasma gondii (T. gondii) is widespread worldwide and has been associated with cognitive deficits in some but not all animal models and in humans. We tested the hypothesis that latent toxoplasmosis is associated with decreased cognitive function in a large cross-sectional dataset, the National Health and Nutrition Examination Survey (NHANES). There were 4178 participants aged 20-59 years, of whom 19.1% had IgG antibodies against T. gondii. Two ordinary least squares (OLS) regression models adjusted for the NHANES complex sampling design and weighted to represent the US population were estimated for simple reaction time, processing speed and short-term memory or attention. The first model included only main effects of latent toxoplasmosis and demographic control variables, and the second added interaction terms between latent toxoplasmosis and the poverty-to-income ratio (PIR), educational attainment and race-ethnicity. We also used multivariate models to assess all three cognitive outcomes in the same model. Although the models evaluating main effects only demonstrated no association between latent toxoplasmosis and the cognitive outcomes, significant interactions between latent toxoplasmosis and the PIR, between latent toxoplasmosis and educational attainment, and between latent toxoplasmosis and race-ethnicity indicated that latent toxoplasmosis may adversely affect cognitive function in certain groups.

Successful conservation strategies have increasingly looked beyond bounded protected areas and toward integrated landscape approaches that conserve biodiversity while maintaining ecosystem services that benefit human communities and food production. More integrated approaches to conservation are particularly timely in agricultural landscapes, where individual farm-level choices can play a significant role in the management of habitat provisioning, nutrient cycling, recreation amenities, carbon sequestration, and the delivery of clean water. This study presents results of an interdisciplinary analysis with shade coffee farmers in the Pico Duarte region of the Dominican Republic. Findings suggest that small farms, as part of a diversified livelihood strategy, maintain a diverse tree canopy, which supports soil conservation and important watershed services. However, high poverty levels and strong economic pressures to convert to high-input, monoculture crops are threatening native tree species biodiversity a...

The production of ecosystem goods and services has increased significantly in the last 100 years, while the capacity of ecosystems to generate supporting and regulating services has decreased. In this context, agriculture and livestock production have become major concerns. At the same time, livestock, particularly dairy cows, play a key role and can serve to improve ecosystems, production, and rural livelihoods. We randomly selected and conducted semistructural interviews with 61 dairy family farmers from four cooperatives in the Encosta da Serra Geral Region of the Atlantic rainforest in Santa Catarina, Brazil. The goal was to analyze their production and viewpoints about environmental variables after adopting management-intensive grazing (MIG). The overall results showed that when farmers changed from semi-confinement and continuous grazing to MIG they perceived improvements in production, livelihoods, and ecosystem services. Moreover, according to farmers’ insights, MIG could be a tool to increase wat...

Purpose (1) To assess the prevalence of rural primary care physician (PCP) bypass, a behavior in which residents travel farther than necessary to obtain health care, (2) To examine the role of community and non-health-care-related characteristics on bypass behavior, and (3) To analyze spatial bypass patterns to determine which rural communities are most affected by bypass. Methods Data came from the Montana Health Matters survey, which gathered self-reported information from Montana residents on their health care utilization, satisfaction with health care services, and community and demographic characteristics. Logistic regression and spatial analysis were used to examine the probability and spatial patterns of bypass. Results Overall, 39% of respondents bypass local health care. Similar to previous studies, dissatisfaction with local health care was found to increase the likelihood of bypass. Dissatisfaction with local shopping also increases the likelihood of bypass, while the number of friends in a community, and commonality with community reduce the likelihood of bypass. Other significant factors associated with bypass include age, income, health, and living in a highly rural community or one with high commuting flows. Conclusions Our results suggest that outshopping theory, in which patients bundle services and shopping for added convenience, extends to primary health care selection. This implies that rural health care selection is multifaceted, and that in addition to perceived satisfaction with local health care, the quality of local shopping and levels of community attachment also influence bypass behavior.

Higher education in the global North, and exported elsewhere, is complicit in driving the planet&rsquo, s socio-ecological crises by teaching how to most effectively marginalize and plunder Earth and human communities. As students and activists within the academic system, we take a firm stand to arrest this cycle, and to redirect education toward teaching how to create conditions for all life to thrive. In this paper, we articulate a research and education agenda for co-constructing knowledge and wisdom, and propose shifts in the &lsquo, ologies from the current, destructive modes to intended regenerative counterparts. We offer to shift from an ontology of separation to that of interconnectedness, from an epistemology of domination to that of egalitarian relationship, and from an axiology of development to that of plural values for world- and meaning-making. Such paradigm shifts reflect the foundational aspirations of the consilient transdiscipline of ecological economics. We analyze several introductory university textbooks in economics, law, and natural sciences, to demonstrate how destructive &lsquo, ologies are taught in North American universities, and how such teaching implicitly undermines critical inquiry and effective challenge. Our strategy for change is to provide a new theoretical framework for education: the regenerative &lsquo, ologies of the Ecozoic&rsquo, based on biophysicality, embedded relationality, pluralism, and the sustainable well-being of all members in the community of life.

BackgroundInfectious diseases might affect cognitive aging and dementia risk, possibly via neuroinflammation. Similarly, risk factors for cardiovascular and cerebrovascular diseases are associated with cognitive function and dementia. We hypothesized that cardiovascular risk factors moderate the association of exposure to infectious diseases with cognitive function.MethodsWe studied 5662 participants aged 20 to 59 years from the third National Health and Nutrition Examination Survey (1988-1994) in the United States. We used linear regression to investigate whether the Framingham general cardiovascular risk index moderated the association of infection burden based on exposure to eight different infectious diseases with cognitive functioning as measured by the Symbol Digit Substitution, Serial Digit Learning, and Reaction Time tests.ResultsThe multiplicative interaction between the infection-burden index and the cardiovascular-risk index was associated with performance on the Symbol Digit Substitution (B = .019 [95% CI: .008, .031], p < .001) but not on the Serial Digit Learning (B = .034 [95% CI: -.025, .094]) or for Reaction Time (B = -.030 [95% CI: -.848, .787]). Participants with a lower cardiovascular risk appeared to be more resilient against the potential adverse effects of higher infection burden on the Symbol Digit Substitution task.ConclusionsParticipants at zero risk for a cardiovascular event in the next 10 years had no differences in processing speed with increasing exposure to infectious disease, whereas participants with higher risk for a cardiovascular event had worse processing speed with increased exposure to infectious disease.

Many studies have addressed whether delinquent behavior is associated with various aspects of schooling and academics. However, this research has been limited to examining unidirectional effects. Building on Thornberry's interactional theory, we develop a conceptual model that posits reciprocal associations among delinquent behavior, school attachment, and academic achievement. The model is tested with two waves from the Add Health data set (n = 9,381) that include measures of transcript grade point average (GPA). The results of a set of structural equation models provide evidence that academic achievement is associated with less delinquent behavior over time, as well as with higher school attachment. However, the effects of delinquency are limited to an attenuating effect on subsequent school attachment; delinquency does not directly influence academic achievement. Thus, we find only partial support for interactional theory.

This study examined the relationship between a European Union (EU) citizens’ degrees of concern toward human trafficking and demographic characteristics, attitudes toward immigrants, and proximity variables (such as geographic region, the number of immigrants, and the percentage of immigrants within their country) using the Eurobarometer 2003 (N = 15,650), which surveyed participants in 15 EU countries. A regression analysis found that older citizens, female citizens, citizens with strong attitudes toward immigrants, citizens who lived in countries that were main routes of illegal immigration, and citizens who lived in regions with more immigrants show more concern about trafficking.

Purpose Posttraumatic stress disorder (PTSD) is an important clinical problem, but little is known about PTSD in rural, nonclinical populations. To better understand PTSD in rural areas, we examined the prevalence and risk and protective factors in urban, rural, and highly rural communities in Montana for both subclinical posttraumatic stress symptoms (PTSS) and PTSD. Methods We compared the prevalence of PTSS and PTSD in urban, rural, and highly rural communities in bivariate and multivariable regression analyses using self-reported cross-sectional survey data from the Montana Health Matters study (N = 3,512), a state-representative household-based survey done in 2010-2011. We also explore potential risk and protective factors for PTSS and PTSD and whether risk and protective factors for each differ by rurality. Findings There were no differences in the level of PTSS by rurality in bivariate or multivariate models, and the bivariate relationship between rurality and PTSD became nonsignificant in a multivariate model. Only locus of control was predictive for PTSS; however, gender, age, marital status, income, employment status, community fit, locus of control, and religiosity were associated with PTSD. Some risk and protective factors operate differently by rurality. Conclusions Although our findings are subject to weaknesses common to cross-sectional data and are based on questionnaire reports, it appears that there are different risk and protective factors for PTSS and PTSD, suggesting that PTSD may be qualitatively different from PTSS. Furthermore, differences in risk and protective factors across urban and rural communities suggest more attention is needed to understand PTSD in rural communities.

The long-term survival of plasma cells is entirely dependent on signals derived from their environment. These extrinsic factors presumably induce and sustain the expression of antiapoptotic proteins of the Bcl-2 family. It is uncertain whether there is specificity among Bcl-2 family members in the survival of plasma cells and whether their expression is linked to specific extrinsic factors. We found here that deletion of the gene encoding the antiapoptotic protein Mcl-1 in plasma cells resulted in rapid depletion of this population in vivo. Furthermore, we found that the receptor BCMA was needed to establish high expression of Mcl-1 in bone marrow but not spleen plasma cells and that establishing this survival pathway preceded the component of plasma cell differentiation that depends on the transcriptional repressor Blimp-1. Our results identify a critical role for Mcl-1 in the maintenance of plasma cells.

Obesity has been on the rise in the US and worldwide for the last several decades. Obesity has been associated with chronic disease development, such as certain types of cancer, type 2 diabetes, cardiovascular disease, and liver diseases. Previously, we reported that obesity promotes DMBA-induced mammary tumor development using the obese Zucker rat model. The intestinal microbiota is composed of a diverse population of obligate and facultative anaerobic microorganisms, and these organisms carry out a broad range of metabolic activities. Obesity has been linked to changes in the intestinal microbiota, but the composition of the bacterial populations in lean and obese Zucker rats has not been carefully studied. Therefore, the objective of this study was to determine the effects of obesity on the gut microbiota in this model. Lean and obese female Zucker rats (n = 16) were fed an AIN-93G-like diet for 8 weeks. Rats were weighed twice weekly, and fecal samples were collected at the beginning and end of the experiment. 16S rRNA gene sequencing was used to evaluate the composition of the fecal bacterial populations. At the outset of the study, the lean rats exhibited much lower ratios of the Firmicutes to Bacteroidetes phyla than the obese rats, but after 60 days, this ratio in the lean rats exceeded that of the obese. This shift was associated with reductions in the Bacteroidaceae, S24-7 and Paraprevotellaceae families in the lean rats. Obese rats also showed increased levels of the genus Akkermansia at day 60. PCoA plots of beta diversity showed clustering of the different test groups, indicating clear differences in intestinal microbiota populations associated with both the time point of the study and the lean or obese status in the Zucker rat model for obesity.

Reaction of the diarylgermylene Ge(ArMe6)2 [ArMe6 = C6H3-2,6-(C6H2-2,4,6-(CH3)3)2] with various inorganic acids (HCN, HN3, and HBF4) led to the facile oxidation of the germanium atom to yield the corresponding Ge(IV) products (ArMe6)2Ge(H)X (X = CN (1), N3 (2), F (3)). The cationic germanium–water complex [(ArMe6)2GeH(OH2)][SO3CF3] (4) was prepared by treating Ge(ArMe6)2 with triflic acid in the presence of trace amounts of moisture. The reactions provide an efficient method of installing a variety of functional groups at a germanium atom and can be used in the preparation of germanium complexes that are analogous to lighter carbon species. The tin species Sn(ArMe6)2 was also oxidized to the Sn(IV) analogue of 3. In all reactions, no evidence of arene elimination was observed, which was in contrast to the reaction of the stannylene (or bulkier germylenes) with hydrogen or ammonia, which yielded H(ArMe6), [(ArMe6)Sn(μ-H)]2, and [(ArMe6)Sn(μ-NH2)]2.

An experimental and DFT investigation of the mechanism of the coupling of methylisocyanide and C-H activation mediated by the germylene (germanediyl) Ge(Ar(Me6))2 (Ar(Me6) = C6H3-2,6(C6H2-2,4,6-Me3)2) showed that it proceeded by initial MeNC adduct formation followed by an isomerization involving the migratory insertion of the MeNC carbon into the Ge-C ligand bond. Addition of excess MeNC led to sequential insertions of two further MeNC molecules into the Ge-C bond. The insertion of the third MeNC leads to methylisocyanide methyl group C-H activation to afford an azagermacyclopentadienyl species. The X-ray crystal structures of the 1:1 (Ar(Me6))2GeCNMe adduct, the first and final insertion products (Ar(Me6))GeC(NMe)Ar(Me6) and (Ar(Me6))GeC(NHMe)C(NMe)C(Ar(Me6))NMe were obtained. The DFT calculations on the reaction pathways represent the first detailed mechanistic study of isocyanide oligomerization by a p-block element species.

Although highly heritable, adult height is also associated with numerous environmental factors, including exposure to infection. Particularly in developing regions of the world, infection burden appears to slow growth during childhood. Using a large database representative of the US population, we examined associations between adult height and leg length and an infection-burden index based on past exposure to Toxocara species, Toxoplasmosis gondii, cytomegalovirus, hepatitis A, hepatitis B, hepatitis C, herpes simplex virus 1, and herpes simplex virus 2. In models controlled for age, sex, educational attainment, socioeconomic status, and race-ethnicity, we found that the infection-burden index predicted height (β=-0.10 [95% CI: -0.15, -0.05], p .0010.001) but not leg length (β=-0.04 [95% CI: -0.12, 0.04], p=0.357). Both sex and race-ethnicity moderated this association. In addition, exposures to Toxocara species, cytomegalovirus, and hepatitis A were each individually associated with reduced height and reduced leg length. While associations between growth and infection have been found principally in children in developing regions of the world, our findings suggest that the effects of infection on height may persist into adulthood even in developed nations.

The facile heterodehydrocoupling of a range of primary or secondary amines and even ammonia with pinacolborane (HBPin) was accomplished using {ArMe6Sn(μ-OMe)}2 (1, ArMe6 = C6H3-2,6-(C6H2-2,4,6-Me3)2) as pre-catalysts for a catalytically active tin(II) hydride. The more sterically hindered pre-catalyst 2, {AriPr4Sn(μ-OMe)}2 (AriPr4 = C6H3-2,6-(C6H3-2,6-iPr2)2) facilitated the dehydrocoupling only of primary amines with HBPin, and at an increased rate relative to the less crowded {ArMe6Sn(μ-OMe)}2. Also presented is {ArMe6Sn(μ-NEt2)}2 (3), which can be converted into the structurally characterizable {ArMe6Sn(μ-NEt2)(μ-H)SnArMe6} (4) via the addition of pinacol borane. This, alongside stoichiometric studies, give insight into the mechanism of the catalysis.

Changes in behaviour and cognition have been associated with latent infection from the apicomplexan protozoan Toxoplasma gondii (Nicolle et Manceaux, 1908) in both animal and human studies. Further, neuropsychiatric disorders such as schizophrenia have also been associated with latent toxoplasmosis. Previously, we found no association between T. gondii immunoglobulin G antibody (IgG) seropositivity and depression in human adults between the ages of 20 and 39 years (n = 1 846) in a sample representative of the United States collected by the Centers for Disease Control as part of a National Health and Nutrition Examination Survey (NHANES) from three datasets collected between 1999-2004. In the present study, we used NHANES data collected between 2009 and 2012 that included subjects aged 20 to 80 years (n = 5 487) and used the Patient Health Questionnaire 9 (PHQ-9) to assess depression with the overall aim of testing the stability of the results of the prior study. In the current study, the seroprevalence of T. gondii was 13%. The percentage of subjects reporting clinical levels of depression assessed with the PHQ-9 was 8%. As before, we found no association between T. gondii IgG seroprevalence and depression (OR = 1.01, 95% CI = 0.81-1.25; p = 0.944) while controlling for sex, educational attainment, race-ethnicity, age, poverty-to-income ratio and cigarette smoking. We also found no positive associations between anti-T. gondii antibody titre and depression (OR = 1.00, 95% CI = 0.96-1.06; p = 0.868). Moreover, we found no association between T. gondii seroprevalence or antibody titre and suicidal ideation (seroprevalence: OR = 1.22, 95% CI = .85-1.75; p = 0.277, titre: OR = 1.05, 95% CI = 0.98-1.14; p = 0.177). Defining depression to also include subjects currently taking antidepressant medication even with non-elevated questionnaires did not find evidence of a positive association between latent toxoplasmosis and depression. In the present study, neither T. gondii seroprevalence nor anti-T. gondii antibody titre was positively associated with depression or suicidal ideation among subjects aged 20 to 80 years.

Significantly reducing weather and climate prediction uncertainty requires global observations with substantially higher information content than present observations provide. While GPS occultations have provided a major advance, GPS observations of the atmosphere are limited by wavelengths chosen specifically to minimize interaction with the atmosphere. Significantly more information can be obtained via satellite to satellite occultations made at wavelengths chosen specifically to characterize the atmosphere. Here we describe such a system that will probe cm- and mmwavelength water vapor absorption lines called the Active Temperature, Ozone and Moisture Microwave Spectrometer (ATOMMS). Profiling both the speed and absorption of light enables ATOMMS to profile temperature, pressure and humidity simultaneously, which GPS occultations cannot do, as well as profile clouds and turbulence. We summarize the ATOMMS concept and its theoretical performance. We describe field measurements made with a prototype ATOMMS instrument and several important capabilities demonstrated with those ground based measurements including retrieving temporal variations in path-averaged water vapor to 1%, in clear, cloudy and rainy conditions, up to optical depths of 17, remotely sensing turbulence and determining rain rates. We conclude with a vision of a future ATOMMS low Earth orbiting satellite constellation designed to take advantage of synergies between observational needs for weather and climate, ATOMMS unprecedented orbital remote sensing capabilities and recent cubesat technological innovations that enable a constellation of dozens of very small spacecraft to achieve many critical, but as yet unfulfilled, monitoring and forecasting needs.

Toxoplasma gondii (T. gondii) seropositivity may be associated with decreased memory in older adults. To further investigate the association between T. gondii seropositivity and memory in non-demented older adults, we obtained serum samples from 114 non-demented older adults evaluated by the Alzheimer’s Disease and Research Center at Washington University in St. Louis Missouri, USA. We determined T. gondii seropositivity and anti-T. gondii IgG antibody titer and examined associations with memory function while controlling for socioeconomic status, education level, age, and apolipoprotein E4 status. There were few associations between T. gondii seropositivity or anti-T. gondii IgG antibodies and memory, although there was some support suggesting an interaction between anti-T. gondii and sex. In the seropositive-only sample, there was an inverse relationship between anti-T. gondii titer and performance on the selective reminding test. Overall, we found little evidence of an association between impaired memory function and T. gondii seropositivity and anti-T gondii IgG antibodies in this sample of non-demented older adults.

We sequenced and annotated the complete 7,170,504-bp genome of a novel secondary metabolite-producing Streptomyces strain, Streptomyces albus SM254, isolated from copper-rich subsurface fluids at ~220-m depth within the Soudan Iron Mine (Soudan, MN, USA).

Toxoplasma gondii (Nicolle et Manceaux, 1908) is an intracellular parasite that can cause ongoing latent infection persisting for the duration of a non-definitive host's life. Affecting approximately one-third of the world's population, latent toxoplasmosis has been associated with neuropsychological outcomes and a previous report suggested an association between latent toxoplasmosis and adult height. Given the large number of people with latent toxoplasmosis and its potential associations with human height, we sought to better understand the association between latent toxoplasmosis and human morphology by evaluating seropositivity for T. gondii and multiple body measures reported in the National Health and Nutrition Examination Survey III (NHANES III) and in the more recent continuous NHANES data sets from the United States Centers for Disease Control and Prevention for which data on T. gondii are available. In these analyses, latent toxoplasmosis was not associated with any of the body measures assessed in the NHANES datasets even after taking into account interactions between latent toxoplasmosis and testosterone suggesting that in these samples, latent toxoplasmosis is not associated with adult morphology including height.

Although research has found a positive relationship between various forms of adolescent religious involvement and educational outcomes, little research has examined connections to educational attainment. Using a nationally representative sample of youth (the National Longitudinal Study of Adolescent Health—Add Health), we examine the extent to which adolescent religiosity facilitates educational attainment (i.e., high school completion and college enrollment) and whether informal mentorships formed during adolescence with religious and nonreligious adults can help explain the link between adolescent religious involvement and educational attainment. The findings confirm that, like academic outcomes, religious youth are more likely to complete high school and enroll in college even when controlling for other individual and interpersonal factors that affect educational attainment. Furthermore, informal mentorships, particularly those with adults who have official religious positions (e.g., priest, minister, rabbi) play an important role in college enrollment.

Neutrophils are an important cellular component of the innate immune system that provides immediate protection to the host from infection. Neutrophil infiltration into inflamed peripheral tissues during infection is beneficial for immunity through phagocytosis of microbes, the release of antimicrobial factors, and secretion of proinflammatory cytokines. Recent reports further suggest that spleen-infiltrating neutrophils play a role in the adaptive immune response by providing survival signals to B cells. However, neutrophils may have detrimental effects on immunity in inflammatory diseases where their recruitment to lymphoid tissues and activation occur abnormally. To determine the contribution of neutrophils that reside in secondary lymphoid tissues to adaptive immunity, direct evaluation of the functional properties of tissue-resident neutrophils is required. We have developed a modified magnetic bead isolation approach for purifying neutrophils from inflamed spleens of autoimmune-prone mice by negative selection. Using this approach, we yielded neutrophils with greater than 90% purity without compromising cell viability. Equally important, the isolation procedure had little effect on the activation of neutrophils and did not impair phagocytic function. Thus, isolation of spleen-resident neutrophils by this optimized approach could be useful for interrogating the functional role of murine neutrophils in normal and abnormal immune responses.

As rural communities undergo substantial demographic and economic changes, understanding the migration intentions and their antecedents of rural elderly persons becomes increasingly important. Using data drawn from a survey of adults from 24 rural Utah communities conducted in 2008, we examine whether rural residents 60 years of age or older plan to remain in their present communities (N= 621). We use structural equation models (SEM) to estimate the relationships between a variety of individual and community-level background measures, including perceptions of local service quality, leaving one's community for health care, Internet use, attachment to and satisfaction with community, and plans to age in place. Results suggest that even as the rural context of economic decline, population loss, and distance to medical services may reduce the viability of staying in a community, a desire to remain in the community is primarily a function of perceptions of the quality of local services and community satisfaction. This research highlights the need to better understand the interplay between the availability of medical services and perceptions of distance as well as to understand the complex relationship between individual and community level characteristics for migration intentions.

The impact of upstream integration and plating process conditions on the electrochemical filling of through-silicon vias (TSV) was investigated. For the same plating process, persistent bottom voiding was eliminated by tuning of the etch process. Thermal desorption mass spectrometry analysis showed the presence of chemical residues consistent with post-etch cleaning chemistry. The coverage of barrier and seed layers deposited by physical vapor deposition was investigated with TEM analysis, and found to be marginal in the vicinity of the bottom of high aspect ratio vias. From the plating side, the process was partitioned and tuned for bottom and top filling. Partial-fill studies were beneficial to identify the onset of bottom up fill for isolated and dense vias. By combining optimized upstream processing and plating process approaches with Generation 3 additive chemistry, bottom up fill was demonstrated for high aspect ratio features > 100 um deep. Finally, significant throughput improvement was shown by tuning the current-density-versus-time profile of the established baseline process.

SAMP1/YitFcs mice serve as a model of Crohn's disease, and we have used them to assess gastritis. Gastritis was compared in SAMP1/YitFcs, AKR, and C57BL/6 mice by histology, immunohistochemistry, and flow cytometry. Gastric acid secretion was measured in ligated stomachs, while anti-parietal cell antibodies were assayed by immunofluorescence and enzyme-linked immunosorbent spot assay. SAMP1/YitFcs mice display a corpus-dominant, chronic gastritis with multifocal aggregates of mononuclear cells consisting of T and B lymphocytes. Relatively few aggregates were observed elsewhere in the stomach. The infiltrates in the oxyntic mucosa were associated with the loss of parietal cell mass. AKR mice, the founder strain of the SAMP1/YitFcs, also have gastritis, although they do not develop ileitis. Genetic studies using SAMP1/YitFcs-C57BL/6 congenic mice showed that the genetic regions regulating ileitis had comparable effects on gastritis. The majority of the cells in the aggregates expressed the T cell marker CD3 or the B cell marker B220. Adoptive transfer of SAMP1/YitFcs CD4+ T helper cells, with or without B cells, into immunodeficient recipients induced a pangastritis and duodenitis. SAMP1/YitFcs and AKR mice manifest hypochlorhydria and anti-parietal cell antibodies. These data suggest that common genetic factors controlling gastroenteric disease in SAMP1/YitFcs mice regulate distinct pathogenic mechanisms causing inflammation in separate sites within the digestive tract.

The veterinary cephalosporin drug ceftiofur is rapidly degraded in the bovine intestinal tract. A cylinder-plate assay was used to detect microbiologically active ceftiofur, and high-performance liquid chromatography-mass spectrometry analysis was used to quantify the amount of ceftiofur remaining after incubation with bovine intestinal anaerobic bacteria, which were isolated from colon contents or feces from 8 cattle. Ninety-six percent of the isolates were able to inactivate ceftiofur to some degree, and 54% actually degraded the drug. None of 9 fungal isolates inactivated or degraded ceftiofur. Facultative and obligate anaerobic bacterial species that inactivated or degraded ceftiofur were identified with Vitek and Biolog systems, respectively. A subset of ceftiofur degraders also degraded the chemically similar drug ceftriaxone. Most of the species of bacteria that degraded ceftiofur belonged to the genera Bacillus and Bacteroides . PCR analysis of bacterial DNA detected specific β-lactamase genes. Bacillus cereus and B. mycoides isolates produced extended-spectrum β-lactamases and metallo-β-lactamases. Seven isolates of Bacteroides spp. produced multiple β-lactamases, including possibly CepA, and metallo-β-lactamases. Isolates of Eubacterium biforme , Bifidobacterium breve , and several Clostridium spp. also produced ceftiofur-degrading β-lactamases. An agar gel overlay technique on isoelectric focusing separations of bacterial lysates showed that β-lactamase enzymes were sufficient to degrade ceftiofur. These results suggest that ceftiofur is inactivated nonenzymatically and degraded enzymatically by multiple β-lactamases from bacteria in the large intestines of cattle.

Antiviral Abs, for example those produced in response to influenza virus infection, are critical for virus neutralization and defense against secondary infection. While the half-life of Abs is short, Ab titers can last a lifetime due to a subset of the Ab-secreting cells (ASCs) that is long lived. However, the mechanisms governing ASC longevity are poorly understood. Here, we have identified a critical role for extrinsic cytokine signals in the survival of respiratory tract ASCs in a mouse model of influenza infection. Irradiation of mice at various time points after influenza virus infection markedly diminished numbers of lung ASCs, suggesting that they are short-lived and require extrinsic factors in order to persist. Neutralization of the TNF superfamily cytokines B lymphocyte stimulator (BLyS; also known as BAFF) and a proliferation-inducing ligand (APRIL) reduced numbers of antiviral ASCs in the lungs and bone marrow, whereas ASCs in the spleen and lung-draining lymph node were surprisingly unaffected. Mice deficient in transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), a receptor for BLyS and APRIL, mounted an initial antiviral B cell response similar to that generated in WT mice but failed to sustain protective Ab titers in the airways and serum, leading to increased susceptibility to secondary viral challenge. These studies highlight the importance of TACI signaling for the maintenance of ASCs and protection against influenza virus infection.

Previous observational and quasi-experimental studies in sub-Saharan Africa have suggested the effectiveness of youth-targeted HIV prevention interventions using sport as an educational tool. No studies have yet assessed the effect of similar programs in the Caribbean. A quasi-experimental trial was conducted to assess the effectiveness of a sports-based intervention in six migrant settlements in the Puerto Plata Province of the Dominican Republic. A total of 397 structured interviews were conducted with 140 adolescents prior to, immediately following, and four months following 10-hour interventions using the Grassroot Soccer curriculum. Interview responses were coded, aggregated into composite scores, and analyzed using logistic regression, adjusting for baseline differences as well as age, sex, community, and descent. At post-intervention, significant differences were observed between groups in HIV-related knowledge (adjOR = 13.02, 95% CI = 8.26, 20.52), reported attitudes (adjOR = 12.01, 95% CI = 7.61, 18.94), and reported communication (adjOR = 3.13, 95% CI = 1.91, 5.12). These differences remained significant at four-month follow-up, though declines in post-intervention knowledge were observed in the Intervention group while gains in knowledge and reported attitudes were observed in the Control group. Results suggest that this sports-based intervention could play a valuable role in HIV prevention efforts in the Caribbean, particularly those targeting early adolescents. Further evaluation of sports-based interventions should include indicators assessing behavioral and biological outcomes, longer-term follow-up, a larger sample, randomization of study participants, and strenuous efforts to minimize loss-to-follow-up.

The aim of this study was to determine how laser in situkeratomileusis (LASIK) affects quality of life (QOL) and to identify factors that may affect satisfaction after LASIK. A total of 104 patients with a mean age of 29±6, treated with LASIK for myopia and astigmatism, were enrolled in a prospective study. High (90%) and low (10%) contrast visual acuity (CVA) were measured under photopic and scotopic conditions before surgery and at 3 months later. A multidimensional QOL scale (Institute for Eye Research multidimensional QOL scale), which assesses psychological characteristics, personality traits, cosmesis, frequency, and tolerance to disturbing visual and ocular symptoms, and overall satisfaction with vision correction, was also used. Paired rank tests were used to compare preoperative and postoperative vision and QOL scores. Correlations and a multiple linear regression were used to describe the relationship between CVA, QOL, and satisfaction after LASIK. Significant postoperative changes included increased satisfaction following LASIK (P

Murine Aim2 and Ifi202 genes (encoding for the Aim2 and p202 proteins) are members of the IFN-inducible Ifi200 gene family. The Aim2 deficiency in mice activates IFN signaling and stimulates the expression of the lupus susceptibility gene, the Ifi202, located within the NZB autoimmunity 2 (Nba2) interval. Given that the deficiency in the expression of the Fcgr2b gene (encoding for the inhibitory FcγRIIB receptor) is associated with increased lupus susceptibility in mice, we investigated whether the Aim2 protein could regulate the expression of Fcgr2b gene. In this article, we report that Aim2 deficiency in mice suppresses the expression of the FcγRIIB receptor. Interestingly, the Fcgr2b-deficient cells expressed increased levels of the IFN-β, activated IFN signaling, and expressed reduced levels of the Aim2 protein. Treatment of splenic cells with IFN-α or -γ reduced levels of the FcγRIIB mRNA and protein and also decreased the activity of the FcγRIIB p(−729/+585) Luc reporter. Moreover, levels of the FcγRIIB receptor were significantly higher in the Stat1-deficient splenic cells than in the wild-type cells. Accordingly, increased expression of IFN-β in lupus-prone B6.Nba2-ABC mice, as compared with non–lupus-prone C57BL/6 (B6) or B6.Nba2-C mice, was associated with reduced expression of the FcγRIIB receptor. Notably, overexpression of the p202 protein in cells decreased the expression of the Aim2 gene, activated the IFN response, and suppressed the expression of the Fcgr2b gene. These observations demonstrate that the expression of Aim2 protein is required to maintain the expression of the Fcgr2b gene and also predict epistatic interactions between the Ifi200 genes and the Fcgr2b gene within the Nba2 interval.

Systemic lupus erythematosus and its preclinical lupus-prone mouse models are autoimmune disorders involving the production of pathogenic autoantibodies. Genetic predisposition to systemic lupus erythematosus results in B cell hyperactivity, survival of self-reactive B cells, and differentiation to autoantibody-secreting plasma cells (PCs). These corrupt B cell responses are, in part, controlled by excess levels of the cytokine BAFF that normally maintains B cell homeostasis and self-tolerance through limited production. B cell maturation Ag (BCMA) is a receptor for BAFF that, under nonautoimmune conditions, is important for sustaining enduring Ab protection by mediating survival of long-lived PCs but is not required for B cell maturation and homeostasis. Through analysis of two different lupus-prone mouse models deficient in BCMA, we identify BCMA as an important factor in regulating peripheral B cell expansion, differentiation, and survival. We demonstrate that a BCMA deficiency combined with the lpr mutation or the murine lupus susceptibility locus Nba2 causes dramatic B cell and PC lymphoproliferation, accelerated autoantibody production, and early lethality. This study unexpectedly reveals that BCMA works to control B cell homeostasis and self-tolerance in systemic autoimmunity.

In zebrafish (Danio rerio), iridophores are specified from neural crest cells and represent a tractable system for examining mechanisms of cell fate and differentiation. Using this system, we have investigated the role of cAMP protein kinase A (PKA) signaling in pigment cell differentiation. Activation of PKA with the adenylyl cyclase activator forskolin reduces the number of differentiated iridophores in wildtype larvae, with insignificant changes to melanophore number. Inhibition of PKA with H89 significantly increases iridophore number, supporting a specific role for PKA during iridophore development. To determine the effects of altering PKA activity on iridophore and melanophore gene expression, we examined expression of iridophore marker pnp4a, melanophore marker mitfa, and the mitfa repressor foxd3. Consistent with our cell counts, forskolin significantly decreased pnp4a expression as detected by in situ hybridization and quantification of pnp4a+ cells. Forskolin had the opposite effect on mitfa and foxd3 gene activity, increasing the area of expression. As mitfa/nacre mutants have extra iridophores as compared to wildtype larvae, we examined the function of mitfa during PKA-sensitive iridophore development. Forskolin treatment of mitfa/nacre mutants did significantly reduce the number of iridophores but to a lesser extent than that observed in treated wildtype larvae. Taken together, our data suggests that PKA inhibits iridophore development in a subset of iridophore precursors, potentially via a foxd3-independent pathway.

In the 50 years or so that polychlorinated biphenyls (PCBs) were manufactured in the USA and elsewhere, they were widely used in numerous applications because of their desirable properties. The purpose of this paper is to review and summarize in one place the factual information about the uses of PCBs, as well as to correct some misconceptions that have arisen over the years. The focus is on applications in the USA for which there is ample documentation. However, use patterns were probably similar worldwide.Review.PCBs were used primarily as electrical insulating fluids in capacitors and transformers and also as hydraulic, heat transfer, and lubricating fluids. PCBs were blended with other chemicals as plasticizers and fire retardants and used in a range of products including caulks, adhesives, plastics, and carbonless copy paper. In the USA, PCBs were manufactured from 1929 through mid-1977, although many products remained in service for decades after the manufacture of PCBs was terminated. This article reviews the historic uses of PCBs in the USA and discusses, where possible, the relative sales volumes. Especially with smaller volume, military, and third-party uses, documenting a use and/or differentiating between a commercial use and an experimental test batch is not possible.A major contribution of this paper is to differentiate reported commercial applications of PCBs that can be documented from those which cannot. Undocumented uses may include actual minor uses as well as reported applications that are unlikely ever to have been commercialized.

Homeostatic scaling of glutamatergic and GABAergic transmission is triggered by prolonged alterations in synaptic neuronal activity. We have previously described a presynaptic mechanism for synaptic homeostasis and plasticity that involves scaling the level of vesicular glutamate (VGLUT1) and gamma-aminobutyric acid (GABA) (VGAT) transporter biosynthesis. These molecular determinants of vesicle filling and quantal size are regulated by neuronal activity in an opposite manner and bi-directionally. Here, we report that a striking induction of VGLUT2 mRNA and synaptic protein is triggered by a prolonged increase in glutamatergic synaptic activity in mature neocortical neuronal networks in vitro together with two determinants of inhibitory synaptic strength, the neuronal activity-regulated pentraxin (Narp), and glutamate decarboxylase (GAD65). Activity-dependent induction of VGLUT2 and Narp exhibits a similar intermediate-early gene response that is blocked by actinomycin D and tetrodotoxin, by inhibitors of ionotropic glutamate receptors and L-type voltage-gated calcium channels, and is dependent on downstream signaling via calmodulin, calcium/calmodulin-dependent protein kinase (CaMK) and extracellular signal-regulated kinase 1/2 (ERK1/2). The co-induction of VGLUT2 and Narp triggered by prolonged gamma-aminobutyric acid type A receptor blockade is independent of brain-derived nerve growth factor and TrkB receptor signaling. VGLUT2 protein induction occurs on a subset of cortically derived synaptic vesicles in excitatory synapses on somata and dendritic processes of multipolar GABAergic interneurons, recognized sites for the clustering of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate receptors by Narp. We propose that VGLUT2 and Narp induction by excitation-transcription coupling leads to increased glutamatergic transmission at synapses on GABAergic inhibitory feedback neurons as part of a coordinated program of Ca(2+)-signal transcription involved in mechanisms of homeostatic plasticity after prolonged hyperactivity.