Using e-modules for acquisition of complex diabetes skills in diabetes care providers in Rwanda.

Type 1 Diabetes (T1D) is life-threatening without appropriate treatment. Though pediatric endocrinology care is limited in Rwanda, a decentralized health system allows access to local non-communicable disease (NCD) nurses through a network of 42 district hospitals. Recent rapid expansion of internet access in the country makes virtual diabetes education initiatives possible. We investigated whether Rwandan NCD nurses receiving diabetes education via online e-modules could make similar educational gains in insulin adjustment skills (IAS) compared to NCD nurses educated in a conference-style setting, and whether they would maintain equivalent competency at 1 year after education. We randomized 21 district hospitals and their NCD nurses to participate in a 1.5-day educational conference centered around care of type 1 diabetes (Group 1), while nurses from the remaining 21 hospitals (Group 2) received accommodation and access to equivalent educational materials in e-module form. Both groups were requested to review initial course materials at 4, 8, and 12 months. Ten-point IAS assessments were administered before and after education or review at each time point. Groups 1 and 2 had equal improvement after education (+2.0 vs. +2.0, p = 0.47) and equal final score at baseline (6.0 vs. 6.0, p = 0.74). However, both groups showed a diminishing improvement over time, so that any gains were lost by 4 months in Group 1 and 8 months in Group 2. Group 1 showed greater attrition in participation over time (19% vs 58% continued participation at one year, p = 0.002). Groups did not differ in subjective confidence in IAS after education. Both groups identified existing or potential access barriers to their respective educational method. While further modifications should be trialed to ensure equitable access and to maintain long-term engagement, online education is a feasible method to teach complex subspecialty skills to providers working in low-resource settings.

Plant species richness at archaeological sites suggests ecological legacy of Indigenous subsistence on the Colorado Plateau.

Humans have both intentional and unintentional impacts on their environment, yet identifying the enduring ecological legacies of past small-scale societies remains difficult, and as such, evidence is sparse. The present study found evidence of an ecological legacy that persists today within an semiarid ecosystem of western North America. Specifically, the richness of ethnographically important plant species is strongly associated with archaeological complexity and ecological diversity at Puebloan sites in a region known as Bears Ears on the Colorado Plateau. A multivariate model including both environmental and archaeological predictors explains 88% of the variation in ethnographic species richness (ESR), with growing degree days and archaeological site complexity having the strongest effects. At least 31 plant species important to five tribal groups (Navajo, Hopi, Zuni, Ute Mountain Ute, and Apache), including the Four Corners potato (Solanum jamesii), goosefoot (Chenopodium sp.), wolfberry (Lycium pallidum), and sumac (Rhus trilobata), occurred at archaeological sites, despite being uncommon across the wider landscape. Our results reveal a clear ecological legacy of past human behavior: even when holding environmental variables constant, ESR increases significantly as a function of past investment in habitation and subsistence. Consequently, we suggest that propagules of some species were transported and cultivated, intentionally or not, establishing populations that persist to this day. Ensuring persistence will require tribal input for conserving and restoring archaeo-ecosystems containing "high-priority" plant species, especially those held sacred as lifeway medicines. This transdisciplinary approach has important implications for resource management planning, especially in areas such as Bears Ears that will experience greater visitation and associated impacts in the near future.

An Initial Assessment of the Utility of Validated Alcohol and Drug Screening Tools in Predicting 30-Day Readmission to Adult General Medicine Wards.

Previous studies have identified drug and alcohol use as risk factors for readmission using claims data, but not by using substance use screening scores. This preliminary study tested the hypothesis that prevalence of 30-day readmission would be higher among patients screening positive on the 10-item Alcohol Use Disorders Identification Test (AUDIT-10) or the 10-item Drug Abuse Screening Test (DAST-10) tools at intake than among the general patient population. Social workers screened 4708 adult inpatients using prescreening questions followed by the AUDIT-10 and/or DAST-10. Patients with positive screens were followed for readmissions within 30 days of discharge. A positive screening score on the AUDIT-10 or DAST-10 instrument at intake was associated with higher risk of readmission to the general medicine wards within 30 days; this relationship appears complex and subject to mediation. Post hoc chart review found that the majority of readmissions among patients with positive screens were not immediately attributable to substance use. Further study is needed to verify these preliminary findings.

Using modeling and rehearsal to teach fire safety to children with autism.

We evaluated the efficacy of an instructional procedure to teach young children with autism to evacuate settings and notify an adult during a fire alarm. A multiple baseline design across children showed that an intervention that included modeling, rehearsal, and praise was effective in teaching fire safety skills. Safety skills generalized to novel settings and maintained during a 5-week follow-up in both training and generalization settings.

The Effectiveness of Direct Instruction in Teaching Students with Autism Spectrum Disorder to Answer "Wh-" Questions.

Research on the effects of Direct Instruction (DI) among students with Autism Spectrum Disorder (ASD) has only recently emerged. A benefit of DI is that it can be implemented with groups of students, which makes it potentially a cost effective method of instruction for some skills. In this study, we examined the effects of DI on teaching secondary students with ASD to answer three "wh-" questions. Using a multiple probe design across behaviors, results indicated the participants mastered two of the three "wh-" question types and made progress with the remaining question type. These results are discussed along with implications for educators instructing students with ASD.

BREATHE: a pilot study of a one-day retreat to reduce burnout among mental health professionals.

OBJECTIVE: Staff burnout is a frequent problem for mental health providers and may be associated with negative outcomes for providers, consumers, and organizations. This study tested an intervention to reduce staff burnout. METHODS: Community mental health providers were invited to participate in a day-long training session to learn methods to reduce burnout. A Web-based survey was given at time of registration, before the intervention, and again six weeks later. RESULTS: Eighty-four providers participated in the training, and follow-up data were available for 74. Six weeks after the day-long training, staff reported significant decreases in emotional exhaustion and depersonalization and significant increases in positive views toward consumers. There were no significant changes in providers' sense of personal accomplishment, job satisfaction, or intention to leave their position. Ninety-one percent of the staff reported the training to be helpful. CONCLUSIONS: This brief intervention is feasible, is acceptable to staff, and may improve burnout and staff attitudes.

Pleiotropic effects of mutations that alter the Sinorhizobium meliloti cytochrome c respiratory system.

Using transposon mutagenesis, mutations have been isolated in several genes (ccdA, cycM, ccmC, ccmB and senC) that play a role in Sinorhizobium meliloti cytochrome metabolism. As in other bacteria, mutations in the S. meliloti ccdA, ccmB and ccmC genes resulted in the absence of all c-type cytochromes. However, the S. meliloti ccdA mutant also lacked cytochrome oxidase aa(3), a defect that does not appear to have been reported for other bacteria. The aa(3)-type cytochromes were also missing from a mutant strain with an insertion into the gene encoding the haem-containing subunit (SU)I of aa(3) cytochrome c oxidase, but not in mutants unable to make SUII or SUIII, indicating that CcdA probably plays a role in assembling SUI. The cytochrome-deficient mutants also had other free-living phenotypes, including a significant decrease in growth rate on rich media and increased motility on minimal media. A senC mutant also had significantly decreased motility, but the motility and growth properties of the cycM mutant were unchanged. Unlike similar mutants in Bradyrhizobium japonicum and Rhizobium leguminosarum, an S. meliloti Rm1021 cycM mutant contained cytochrome oxidase aa(3). Cytochrome maturation in strain Rm1021 appeared to be similar to maturation in other rhizobia, but there were some differences in the cytochrome composition of the strain, and respiration chain function and assembly.

IL-10 inhibits lipopolysaccharide-induced CD40 gene expression through induction of suppressor of cytokine signaling-3.

Costimulation between T cells and APCs is required for adaptive immune responses. CD40, an important costimulatory molecule, is expressed on a variety of cell types, including macrophages and microglia. The aberrant expression of CD40 is implicated in diseases including multiple sclerosis, rheumatoid arthritis, and Alzheimer's disease, and inhibition of CD40 signaling has beneficial effects in a number of animal models of autoimmune diseases. In this study, we discovered that IL-10, a cytokine with anti-inflammatory properties, inhibits LPS-induced CD40 gene expression. We previously demonstrated that LPS induction of CD40 in macrophages/microglia involves both NF-kappaB activation and LPS-induced production of IFN-beta, which subsequently activates STAT-1alpha. IL-10 inhibits LPS-induced IFN-beta gene expression and subsequent STAT-1alpha activation, but does not affect NF-kappaB activation. Our results also demonstrate that IL-10 inhibits LPS-induced recruitment of STAT-1alpha, RNA polymerase II, and the coactivators CREB binding protein and p300 to the CD40 promoter, as well as inhibiting permissive histone H3 acetylation (AcH3). IL-10 and LPS synergize to induce suppressor of cytokine signaling (SOCS)-3 gene expression in macrophages and microglia. Ectopic expression of SOCS-3 attenuates LPS-induced STAT activation, and inhibits LPS-induced CD40 gene expression, comparable to that seen by IL-10. These results indicate that SOCS-3 plays an important role in the negative regulation of LPS-induced CD40 gene expression by IL-10.

IFN-beta-induced SOCS-1 negatively regulates CD40 gene expression in macrophages and microglia.

Costimulation between T cells and antigen-presenting cells is required for adaptive immune responses. CD40, a costimulatory molecule, is expressed in macrophages and microglia. The aberrant expression of CD40 is involved in human diseases including multiple sclerosis, rheumatoid arthritis, and Alzheimer's disease. CD40 expression is induced by a variety of stimuli, including IFN-gamma and lipopolysaccharide (LPS). In this study, we describe the molecular basis by which IFN-beta, a cytokine with immunomodulatory properties, regulates CD40 gene expression. IFN-beta induces CD40 expression in macrophages and microglia at the transcriptional level, and GAS elements in the CD40 promoter are required for IFN-beta-induced CD40 promoter activity. The critical role of signal transducers and activators of transcription-1alpha (STAT-1alpha) in this response was confirmed by utilizing primary microglia from STAT-1alpha deficient mice. IFN-beta induces suppressor of cytokine signaling-1 (SOCS-1) gene expression, which inhibits cytokine signaling by inhibiting activation of STAT proteins. The ectopic expression of SOCS-1 abrogates IFN-beta-mediated STAT-1alpha activation and inhibits IFN-beta-induced CD40 expression. IFN-beta-induced recruitment of STAT-1alpha and RNA Pol II and permissive histone modifications on the CD40 promoter are also inhibited by SOCS-1 overexpression. These novel results indicate that IFN-beta-induced SOCS-1 plays an important role in the negative regulation of IFN-beta-induced CD40 gene expression.

LPS induces CD40 gene expression through the activation of NF-kappaB and STAT-1alpha in macrophages and microglia.

CD40 is expressed on various immune cells, including macrophages and microglia. Aberrant expression of CD40 is associated with autoimmune inflammatory diseases such as multiple sclerosis and rheumatoid arthritis. Interaction of Toll-like receptor-4 (TLR4) with the Gram-negative bacteria endotoxin lipopolysaccharide (LPS) results in the induction of an array of immune response genes. In this study, we describe that LPS is a strong inducer of CD40 expression in macrophages and microglia, which occurs at the transcriptional level and involves the activation of the transcription factors nuclear factor-kappaB (NF-kappaB) and signal transducer and activator of transcription 1alpha (STAT-1alpha). LPS-induced CD40 expression involves the endogenous production of the cytokine interferon-beta (IFN-beta), which contributes to CD40 expression by the activation of STAT-1alpha. Blocking IFN-beta-induced activation of STAT-1alpha by IFN-beta-neutralizing antibody reduces LPS-induced CD40 gene expression. Furthermore, LPS induces acetylation and phosphorylation of histones H3 and H4 and the recruitment of NF-kappaB, STAT-1alpha, and RNA polymerase II on the CD40 promoter in vivo in a time-dependent manner, all events important for CD40 gene transcription. These results indicate that both LPS-induced NF-kappaB activation and endogenous production of IFN-beta that subsequently induces STAT-1alpha activation play critical roles in the transcriptional activation of the CD40 gene by LPS.

Increasing rates of nasal carriage of methicillin-resistant Staphylococcus aureus in healthy children.

BACKGROUND: Prior studies, including one from our institution performed in 2001, suggest that nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) occurs infrequently in the healthy pediatric population (0.2-2.2%). However, infections caused by community-associated MRSA have increased remarkably in recent years. As a result, we restudied the prevalence of MRSA nasal colonization in healthy children, comparing results from 2001 and 2004. PATIENTS AND METHODS: Nasal swabs were collected from 500 children presenting for health maintenance visits. Samples were cultured quantitatively, and MRSA isolates were confirmed by growth on selective media, coagulase testing and the presence of the mecA resistance gene. MRSA isolates were further analyzed for antibiotic susceptibilities, genetic relatedness by pulsed field gel electrophoresis and polymerase chain reaction for the detection of the gene encoding Panton-Valentine leukocidin. RESULTS: There were 182 children (36.4%) colonized with S. aureus, and 46 (9.2%) colonized with MRSA. This is significantly higher than the MRSA colonization rate in 2001 (0.8%; P < 0.001). There were no significant associations between potential risk factors and MRSA colonization except for having a family member work in a hospital (odds ratio, 2.0; 95% confidence interval, 1.03-4.1). Pulsed field gel electrophoresis revealed heterogeneity of circulating strains, and the Panton-Valentine leukocidin gene locus was detected in 10 of 46 MRSA isolates (22%). CONCLUSION: Nasal MRSA colonization in healthy children in Nashville has increased significantly in the past 3 years. As colonization typically precedes infection, this increase may be a major factor in the emergence of community-associated MRSA as a pathogen of healthy children.

Class II major histocompatibility complex transactivator (CIITA) inhibits matrix metalloproteinase-9 gene expression.

Matrix metalloproteinases (MMPs) are a family of structurally related proteins with the collective capability to degrade all components of the extracellular matrix. Although MMP-mediated degradation of the extracellular matrix occurs physiologically, numerous pathological conditions exhibit increased MMP levels and excessive matrix degradation. Previous work from our laboratory has shown that interferon-gamma inhibits MMP-9 expression in a manner dependent upon STAT-1alpha. Here we extend our previous observations and show that the class II major histocompatibility complex transactivator (CIITA), a transcriptional target of STAT-1alpha, is also capable of inhibiting MMP-9 expression. By using stable cell lines that inducibly express CIITA or various mutant forms of CIITA, we show that CIITA requires the ability to bind the CREB-binding protein (CBP) to effectively inhibit MMP-9 expression. Furthermore, we show that CIITA-mediated inhibition of the MMP-9 gene does not rely on the transcriptional capability of CIITA. These findings support a model wherein CIITA inhibits MMP-9 expression by binding to and sequestering CBP, which reduces the levels of CBP at the MMP-9 promoter, inhibits levels of acetylated histone 3 at the MMP-9 promoter, and subsequently inhibits MMP-9 expression.

A comparative study of four serological tumor markers for the detection of breast cancer.

Breast cancer is currently the third most common cause of cancer in the world. Circulating tumor antigens are often used as a minimally invasive tool for noting breast cancer progression. The objective of this study was to compare four tumor antigens (CA 15-3, CA 27.29, alpha-fetoprotein [AFP], and carcinoembryonic antigen [CEA]) for their diagnostic efficacy in breast cancer patients. It was hypothesized that CA 15-3 would proved to be superior to CA 27.29, CEA, and AFP in assay performance. Tumor marker assays were performed according to the manufacturers' directions. Assays used in this study were CA 15-3 and CA 27.29 (Fujirebio Diagnostics/Centocor Inc.), AFP (Abbott Inc.), and CEA (Hybritech Inc.). A total of 554 patient samples were obtained from an area hospital, plus 200 healthy adult samples which were used for the determination of normal reference intervals. The patients included patients with no disease (184), with non-malignant disease (11), with breast cancer (87), and with other types of cancer (272). Diagnostic percent sensitivities for each marker were: CA 15-3 (63%), CA 27.29 (39%), CEA (22%), and AFP (22%). Diagnostic specificities for each marker were comparable, ranging from 80-88%. Analytical parameters were evaluated for the assays and compared favorably. We concluded that CA 15-3 was the best tumor antigen for use as a diagnostic aid and monitoring agent.