Obesity emerged as a risk factor for morbidity and mortality related to 2009 pandemic influenza A (H1N1) infection. However, few studies examine the immune responses to H1N1 vaccine among children and adults of various body mass indices (BMI). Pooling data from 3 trials of unadjuvanted split-virus H1N1 A/California/07/2009 influenza vaccines, we analyzed serologic responses of participants stratified by BMI grouping. A single vaccine dose produced higher hemagglutination inhibition antibody titers at day 21 in obese compared to nonobese adults, but there were no significant differences in responses to H1N1 vaccine among children or adults of various BMI following 2 doses.
body mass index; influenza vaccine; immune response; obesity
Hand hygiene is an effective, low-cost intervention that prevents the spread of multidrug-resistant bacteria. Despite mandatory education and reminders, compliance by physicians in our hospital remained stubbornly low. Our objective was to study whether surveillance by our unit coordinator (secretary) paired with regular feedback to chiefs of service would increase physician hand hygiene compliance in the ICU.
The ICU unit coordinator was trained to observe and measure hand hygiene compliance. Data were collected on hand hygiene compliance at room entry and exit for 9 months. Percentage compliance for each medical and surgical subspecialty was reported to chiefs of service at the end of each month. Comparative rankings by service were widely distributed throughout the physician organization and the medical center.
The hand hygiene compliance rate among physicians increased from 65.1 % to 91.6 % during the study period (p <0.0001). More importantly in the succeeding 24 months after study completion, physician hand hygiene compliance remained >90 % in every month.
Physician hand hygiene compliance increased as a consequence of the surveillance conducted by a full-time ICU team member, leading to a highly significant increase in the number of observations. In turn, this allowed for specific comparative monthly feedback to individual chiefs of service. Over the next 2 years after the study ended, these gains were sustained, suggesting an enduring culture change in physician behavior.
Although research shows treatment for alcohol and drug problems can be effective, persons without stable housing that supports recovery are at risk for relapse. Recovery residences (RRs) for drug and alcohol problems are a growing response to the need for alcohol- and drug-free living environments that support sustained recovery. Research on RRs offers an opportunity to examine how integration of these individuals into a supportive, empowering environment has beneficial impacts on substance use, housing, and other outcomes, as well as benefits for the surrounding community. Research can also lead to the identification of operations and practices within houses that maximize favorable outcomes for residents. However, research on RRs also presents significant obstacles and challenges. Based on our experiences conducting recovery home research for decades, we present suggestions for addressing some of the unique challenges encountered in this type of research.
Recovery Residence; Recovery Home; Oxford House; Sober Living House
While persons with dementia are frequently hospitalized, relatively little is known about the health profile, patterns of health care use, and mortality rates for patients with dementia who access care in the emergency department (ED). We linked data from our hospital system with Medicare and Medicaid claims, Minimum Data Set, and Outcome and Assessment Information Set data to evaluate 175,652 ED visits made by 10,354 individuals with dementia and 15,020 individuals without dementia over 11 years. Survival rates after ED visits and associated charges were examined. Patients with dementia visited the ED more frequently, were hospitalized more often than patients without dementia, and had an increased odds of returning to the ED within 30 days of an index ED visit compared to persons who never had a dementia diagnosis (odds ratio 2.29, P<0.001). Survival rates differed significantly between patients by dementia status (P<0.001). Mean Medicare payments for ED services were significantly higher among patients with dementia. These results show that older adults with dementia are frequent ED visitors who have greater comorbidity, incur higher charges, are admitted to hospitals at higher rates, return to EDs at higher rates, and have higher mortality after an ED visit than patients without dementia.
survival rate; emergency department; dementia diagnosis
The California Leafy Green Products Handler Marketing Agreement (LGMA) requires leafy green crops within 9 m of the edge of a flooded field not be harvested due to potential contamination (California Leafy Green Products Handler Marketing Board, Commodity Specific Flood Safety Guidelines for the Production and Harvest of Lettuce and Leafy Greens, 2012). Further, previously flooded soils should not be replanted for 60 days. In this study, the suitability of the LGMA metrics for farms in the Mid-Atlantic region of the United States was evaluated. The upper end of a spinach bed (in Beltsville, MD) established on a −5% grade was flooded with water containing 6 log CFU/ml Escherichia coli to model a worst-case scenario of bacterial movement through soil. Escherichia coli prevalence in soil and on foliar tissue was determined by most probable number (MPN) analysis at distances up to 9 m from the edge of the flood for 63 days. While E. coli was quickly detected at the 9-m distance within 1 day in the spring trial and within 3 days in the fall trial, no E. coli was detected on plants outside the flood zone after 14 days. On day 63 for the two trials, E. coli populations in the flood zone soil were higher in the fall than in the spring. Regression analysis predicted that the time required for a 3-log MPN/g (dry weight) decrease in E. coli populations inside the flood zone was within the 60-day LGMA guideline in the spring but would require 90 days in the fall. Overall, data suggest that the current guidelines should be revised to include considerations of field and weather conditions that may promote bacterial movement and survival.
IMPORTANCE This study tracked the movement of Escherichia coli from floodwater across a horizontal plane of soil and the potential for the contamination of distant leafy green produce. The purpose of this study was to address the validity of the California Leafy Green Products Handler Marketing Agreement recommendations for the harvest of leafy green crops after a flooding event. These recommendations were based on the turning radius of farming equipment but did not take into consideration the potential subsurface movement of pathogens in the water through soil. This research shows that further considerations of field slope, temperature, and additional rainfall events may be necessary to provide appropriate guidelines to prevent the harvest of leafy green crops contaminated by enteric pathogens in floodwaters. This study may be used to provide a framework for comprehensive recommendations to growers for good harvesting practices after a flooding event.
We examined the effect of knee osteoarthritis on the rate of torque development (RTD) of the knee extensors in older adults with advanced-stage knee osteoarthritis (OA; n=15) and recreationally-active controls (n=15) of similar age, sex and health status, as well as the relationship between RTD and the size and contractility of single muscle fibers. OA participants had lower RTD when expressed in absolute terms (Nm/ms). There were sex differences in peak RTD (P<0.05), with greater RTD in men, but no group by sex interaction effects for any variables. The lower RTD in OA versus controls was not explained by variation between groups in the fiber type admixture of the muscle, and was mitigated when RTD was normalized to peak torque (PT). In knee OA volunteers, we found strong correlations between the RTD expressed relative to PT and the velocity of contraction of single myosin heavy chain (MHC) I and IIA/X muscle fibers (r=0.652 and 0.862; both P<0.05) and power output of MHC I fibers (r=0.642; P<0.05). In controls, RTD relative to PT was related to fiber cross-sectional area of MHC IIA/X fibers (r=0.707; P<0.05), but not measures of single fiber contractile performance. To our knowledge, these results represent the first demonstration that variation in whole muscle contractile kinetics in patients with advanced-stage knee osteoarthritis and healthy older adults is related, in part, to the size and function of single muscle fibers.
single muscle fiber; velocity; skinned fiber
This is a perspective from the peer session on stable isotope labelling and fluxomics at the Australian & New Zealand Metabolomics Conference (ANZMET) held from 30 March to 1 April 2016 at La Trobe University, Melbourne, Australia. This report summarizes the key points raised in the peer session which focused on the advantages of using stable isotopes in modern metabolomics and the challenges in conducting flux analyses. The session highlighted the utility of stable isotope labelling in generating reference standards for metabolite identification, absolute quantification, and in the measurement of the dynamic activity of metabolic pathways. The advantages and disadvantages of different approaches of fluxomics analyses including flux balance analysis, metabolic flux analysis and kinetic flux profiling were also discussed along with the use of stable isotope labelling in in vivo dynamic metabolomics. A number of crucial technical considerations for designing experiments and analyzing data with stable isotope labelling were discussed which included replication, instrumentation, methods of labelling, tracer dilution and data analysis. This report reflects the current viewpoint on the use of stable isotope labelling in metabolomics experiments, identifying it as a great tool with the potential to improve biological interpretation of metabolomics data in a number of ways.
stable-isotope labelling; metabolomics; fluxomics
A simple method for tracing carbon fixation and lipid synthesis in microalgae was developed using a combination of solid-phase extraction (SPE) and negative ion chemical ionisation gas chromatography mass spectrometry (NCI-GC-MS). NCI-GC-MS is an extremely sensitive technique that can produce an unfragmented molecular ion making this technique particularly useful for stable isotope enrichment studies. Derivatisation of fatty acids using pentafluorobenzyl bromide (PFBBr) allows the coupling of the high separation efficiency of GC and the measurement of unfragmented molecular ions for each of the fatty acids by single quadrupole MS. The key is that isotope spectra can be measured without interference from co-eluting fatty acids or other molecules. Pre-fractionation of lipid extracts by SPE allows the measurement of 13C isotope incorporation into the three main lipid classes (phospholipids, glycolipids, neutral lipids) in microalgae thus allowing the study of complex lipid biochemistry using relatively straightforward analytical technology. The high selectivity of GC is necessary as it allows the collection of mass spectra for individual fatty acids, including cis/trans isomers, of the PFB-derivatised fatty acids. The combination of solid-phase extraction and GC-MS enables the accurate determination of 13C incorporation into each lipid pool. Three solvent extraction protocols that are commonly used in lipidomics were also evaluated and are described here with regard to extraction efficiencies for lipid analysis in microalgae.
13C stable isotope measurement; chemical ionisation; gas chromatography; mass spectrometry; solid-phase extractions; algae; lipids
Prolactin (PRL) is well characterized for its roles in initiation and maintenance of lactation, and it also suppresses stress-induced responses. Feeding a high-fat diet (HFD) disrupts activity of the hypothalamic-pituitary-adrenal (HPA) axis. Whether PRL regulates HPA axis activation under HFD feeding is not clear. Male and female wildtype (WT) and PRL knockout (KO) mice were fed either a standard low-fat diet (LFD) or HFD for 12 weeks. Circulating corticosterone (CORT) levels were measured before, during, and after mice were subjected to an acute restraint stress or remained in their home cages as no stress controls. HFD feeding increased leptin levels, but the increase was lower in KO than in WT mice. All stressed female groups and only LFD-fed stressed males had elevated CORT levels compared to their no stress same-sex counterparts regardless of genotype. These results indicated that HFD consumption blunted the HPA axis response to acute stress in males but not females. Additionally, basal hypothalamic CRH content was lower in HFD than LFD males, but was similar among female groups. Furthermore, although basal CORT levels were similar among KO and WT groups, CORT levels were higher in KO mice than their WT counterparts during stress, suggesting that loss of PRL led to greater HPA axis activation. Basal PRL receptor mRNA levels in the choroid plexus were higher in HFD than LFD same-sex counterparts, suggesting activation of central PRL’s action by HFD feeding in both males and females. Current results confirmed PRL’s roles in suppression of the stress-induced HPA axis activation. Although HFD feeding activated central PRL’s action in both sexes, only the male HPA axis was dampened by HFD feeding.
We present DADA2, a software package that models and corrects Illumina-sequenced amplicon errors. DADA2 infers sample sequences exactly, without coarse-graining into OTUs, and resolves differences of as little as one nucleotide. In several mock communities DADA2 identified more real variants and output fewer spurious sequences than other methods. We applied DADA2 to vaginal samples from a cohort of pregnant women, revealing a diversity of previously undetected Lactobacillus crispatus variants.
The treatment goal for recurrent malignant gliomas centers on disease stabilization while minimizing therapy-related side effects. Metronomic dosing of cytotoxic chemotherapy has emerged as a promising option to achieve this objective.
This phase I study was performed using metronomic temozolomide (mTMZ) at 25 or 50 mg/m2/day continuously in 42-day cycles. Correlative studies were incorporated using arterial spin labeling MRI to assess tumor blood flow, analysis of matrix metalloproteinase-2 (MMP-2) and MMP-9 activities in the cerebrospinal fluid (CSF) as surrogates for tumor angiogenesis and invasion, as well as determination of CSF soluble interleukin-2 receptor alpha (sIL-2Rα) levels as a marker of immune modulation.
Nine subjects were enrolled and toxicity consisted of primarily grade 1 or 2 hematological and gastrointestinal side effects; only one patient had a grade 3 elevated liver enzyme level that was reversible. Tumor blood flow was variable across subjects and time, with two experiencing a transient increase before a decrease to below baseline level while one exhibited a gradual drop in blood flow over time. MMP-2 activity correlated with overall survival but not with progression free survival, while MMP-9 activity did not correlate with either outcome parameters. Baseline CSF sIL-2Rα level was inversely correlated with time from initial diagnosis to first progression, suggesting that subjects with higher sIL-2Rα may have more aggressive disease. But they lived longer when treated with mTMZ, probably due to drug-related changes in T-cell constituency.
mTMZ possesses efficacy against recurrent malignant gliomas by altering blood flow, slowing invasion and modulating antitumor immune function.
Metronomic temozolomide; Recurrent glioma; Arterial spin labeling; Matrix metalloproteinase; Interleukin
The health literacy demands of the healthcare system often exceed the health literacy skills of Americans. This article reviews the development of the Health Literacy Universal Precautions (HLUP) Toolkit, commissioned by the Agency for Healthcare Research and Quality and designed to help primary care practices structure the delivery of care as if every patient may have limited health literacy. The development of the toolkit spanned 2 years and consisted of 3 major tasks: (1) developing individual tools (modules explaining how to use or implement a strategy to minimize the effects of low health literacy), using existing health literacy resources when possible, (2) testing individual tools in clinical practice and assembling them into a prototype toolkit, and (3) testing the prototype toolkit in clinical practice. Testing revealed that practices will use tools that are concise and actionable and are not perceived as being resource intensive. Conducting practice self-assessments and generating enthusiasm among staff were key elements for successful implementation. Implementing practice changes required more time than anticipated and some knowledge of quality improvement techniques. In sum, the HLUP Toolkit holds promise as a means of improving primary care for people with limited health literacy, but further testing is needed.
Health literacy; Quality improvement
High-throughput sequencing of PCR-amplified taxonomic markers (like the 16S rRNA gene) has enabled a new level of analysis of complex bacterial communities known as microbiomes. Many tools exist to quantify and compare abundance levels or OTU composition of communities in different conditions. The sequencing reads have to be denoised and assigned to the closest taxa from a reference database. Common approaches use a notion of 97% similarity and normalize the data by subsampling to equalize library sizes. In this paper, we show that statistical models allow more accurate abundance estimates. By providing a complete workflow in R, we enable the user to do sophisticated downstream statistical analyses, whether parametric or nonparametric. We provide examples of using the R packages dada2, phyloseq, DESeq2, ggplot2 and vegan to filter, visualize and test microbiome data. We also provide examples of supervised analyses using random forests and nonparametric testing using community networks and the ggnetwork package.
microbiome; taxonomy; community analysis
The mosquito Aedes aegypti (L.) is a major vector of viral diseases like dengue fever, Zika and chikungunya. Aedes aegypti exhibits high morphological and behavioral variation, some of which is thought to be of epidemiological significance. Globally distributed domestic Ae. aegypti have often been grouped into (i) the very pale variety queenslandensis and (ii) the type form. Because the two color forms co-occur across most of their range, there is interest in understanding how freely they interbreed. This knowledge is particularly important for control strategies that rely on mating compatibilities between the release and target mosquitoes, such as Wolbachia releases and SIT. To address this question, we analyzed nuclear and mitochondrial genome-wide variation in the co-occurring pale and type Ae. aegypti from northern Queensland (Australia) and Singapore.
We typed 74 individuals at a 1170 bp-long mitochondrial sequence and at 16,569 nuclear SNPs using a customized double-digest RAD sequencing. 11/29 genotyped individuals from Singapore and 11/45 from Queensland were identified as var. queenslandensis based on the diagnostic scaling patterns. We found 24 different mitochondrial haplotypes, seven of which were shared between the two forms. Multivariate genetic clustering based on nuclear SNPs corresponded to individuals’ geographic location, not their color. Several family groups consisted of both forms and three queenslandensis individuals were Wolbachia infected, indicating previous breeding with the type form which has been used to introduce Wolbachia into Ae. aegypti populations.
Aedes aegypti queenslandensis are genomically indistinguishable from the type form, which points to these forms freely interbreeding at least in Australia and Singapore. Based on our findings, it is unlikely that the presence of very pale Ae. aegypti will affect the success of Aedes control programs based on Wolbachia-infected, sterile or RIDL mosquitoes.
Aedes aegypti, the most important vector of dengue and Zika, greatly varies in body color and behavior. Two domestic forms of this mosquito, the very pale queenslandensis and the browner type, are often found together in populations around the globe. Knowing how freely they interbreed is important for the control strategies such as releases of Wolbachia and sterile males. To address this question, we used RAD sequencing to genotype samples of both forms collected in Singapore and northern Queensland. We did not find any association between the mitochondrial or nuclear genome-wide variation and color variation in these populations. Rather, “paleness” is likely to be a quantitative trait under some environmental influence. We also detected several queenslandensis individuals with the Wolbachia infection, indicating free interbreeding with the type form which has been used to introduce Wolbachia into Ae. aegypti populations. Overall, our data show that the very pale queenslandensis are not genomically separate, and their presence is unlikely to affect the success of Aedes control programs based on Wolbachia-infected, sterile or RIDL mosquitoes.
Hedgehog (Hh) proteins function in cell/cell signaling processes linked to human embryo development and the progression of several types of cancer. Here we describe an optical assay of hedgehog cholesterolysis, a unique autoprocessing event critical for Hh function. The assay uses a recombinant FRET-active hedgehog precursor whose cholesterolysis can be monitored continuously in multi-well plates (dynamic range, 4; Z’, 0.7), offering advantages in throughput over conventional SDS-PAGE assays. Application of the optical assay in a pilot small molecule screen produced a novel cholesterolysis inhibitor (apparent IC50, 5×10−6 M) that appears to inactivate hedgehog covalently by a SNAr mechanism.
Deficits in quality end-of-life care for nursing home (NH) residents are well known. Palliative care is promoted as an approach to improve quality. The Palliative Care Survey (PCS) is designed to measure NH staff palliative care knowledge and practice.
To comparing palliative care knowledge and practices across NH staff roles using the PCS, and to examine relationships between facility characteristics and PCS scores.
The PCS was administered to frontline NH staff—certified nursing assistants (CNAs), licensed practical nurses (LPNs), registered nurses (RNs), and social workers (SWs)—in 51 facilities in 2012. Descriptive statistics were calculated by job role. Linear mixed effects models were used to identify facility and individual factors associated with palliative care practice and knowledge.
The analytic sample included 1200 surveys. CNAs had significantly lower practice and knowledge scores compared to LPNs, RNs, and SWs (P < 0.05). LPNs had significantly lower psychological, end-of-life, and total knowledge scores than RNs (P < 0.05 for all). Although knowledge about physical symptoms was uniformly high, end-of-life knowledge was notably low for all staff. A one-point higher facility star rating was significantly associated with a 0.06 increase in family communication score (P = 0.003; 95% CI: 0.02–0.09; SE = 0.02). Higher penetration of hospice in the NH was associated with higher end-of-life knowledge (P = 0.003; parameter estimate = 0.006; 95% CI: 0.002–0.010; SE = 0.002). Sixty-two percent of respondents stated that, with additional training, they would be interested in being leaders in palliative care.
Given observed differences in palliative care practice and knowledge scores by staff training, it appears the PCS is a useful tool to assess NH staff. Low end-of-life knowledge scores represent an important target for quality improvement.
Nursing home; palliative care; end of life; hospice
Previous studies showed that sub-MIC levels of β-lactam antibiotics stimulate biofilm formation in most methicillin-resistant Staphylococcus aureus (MRSA) strains. Here, we investigated this process by measuring the effects of sub-MIC amoxicillin on biofilm formation by the epidemic community-associated MRSA strain USA300. We found that sub-MIC amoxicillin increased the ability of USA300 cells to attach to surfaces and form biofilms under both static and flow conditions. We also found that USA300 biofilms cultured in sub-MIC amoxicillin were thicker, contained more pillar and channel structures, and were less porous than biofilms cultured without antibiotic. Biofilm formation in sub-MIC amoxicillin correlated with the production of extracellular DNA (eDNA). However, eDNA released by amoxicillin-induced cell lysis alone was evidently not sufficient to stimulate biofilm. Sub-MIC levels of two other cell wall-active agents with different mechanisms of action—d-cycloserine and fosfomycin—also stimulated eDNA-dependent biofilm, suggesting that biofilm formation may be a mechanistic adaptation to cell wall stress. Screening a USA300 mariner transposon library for mutants deficient in biofilm formation in sub-MIC amoxicillin identified numerous known mediators of S. aureus β-lactam resistance and biofilm formation, as well as novel genes not previously associated with these phenotypes. Our results link cell wall stress and biofilm formation in MRSA and suggest that eDNA-dependent biofilm formation by strain USA300 in low-dose amoxicillin is an inducible phenotype that can be used to identify novel genes impacting MRSA β-lactam resistance and biofilm formation.
Face cleanliness is a core component of the SAFE (Surgery, Antibiotics, Facial cleanliness, and Environmental improvements) strategy for trachoma control. Understanding knowledge, attitudes, and behaviors related to face washing may be helpful for designing effective interventions for improving facial cleanliness.
In April 2014, a mixed methods study including focus groups and a quantitative cross-sectional study was conducted in the East Gojjam zone of the Amhara region of Ethiopia. Participants were asked about face washing practices, motivations for face washing, use of soap (which may reduce bacterial load), and fly control strategies.
Overall, both knowledge and reported practice of face washing was high. Participants reported they knew that washing their own face and their children’s faces daily was important for hygiene and infection control. Although participants reported high knowledge of the importance of soap for face washing, quantitative data revealed strong variations by community in the use of soap for face washing, ranging from 4.4% to 82.2% of households reporting using soap for face washing. Cost and forgetfulness were cited as barriers to the use of soap for face washing. Keeping flies from landing on children was a commonly cited motivator for regular face washing, as was trachoma prevention.
Interventions aiming to improve facial cleanliness for trachoma prevention should focus on habit formation (to address forgetfulness) and address barriers to the use of soap, such as reducing cost. Interventions that focus solely on improving knowledge may not be effective for changing face-washing behaviors.
Facial cleanliness is a core component of the SAFE (Surgery, Antibiotics, Facial cleanliness, and Environmental improvements) strategy for trachoma control. We conducted a mixed methods study in a trachoma hyperendemic region of rural Ethiopia to better understand knowledge, attitudes, and behaviors related to face washing. Overall, knowledge of the benefits of face washing was high, and participants reported regularly engaging in face washing practices. However, the use of soap for face washing varied more between communities. Participants cited cost and forgetting to use soap as the primary barriers to using soap for face washing. Trachoma prevention, including keeping flies from landing on children’s faces, was a commonly-cited motivator for face washing discussed in focus groups. Given the near-universal knowledge of the benefits of face washing, interventions focused on changing face washing behavior for trachoma control should focus on habit formation and removal of barriers to the use of soap rather than simply educational interventions.
C-reactive protein (CRP) is a risk factor for cardiovascular disease and mortality; it is known to be positively associated with obesity but there is some evidence that this association differs by race or sex. We used nationally representative data of adults aged >50 years to investigate sex and race modifiers of the associations between obesity and CRP in non-Hispanic White males (n=3,517) and females (n=4,658), and non-Hispanic Black males (n=464) and females (n=826). Using multiple linear regression models with the natural logarithm of CRP as the dependent variable, we sequentially included body mass index (BMI), a body shape index (ABSI), and socioeconomic, health and health behavior covariates in the model. The association between BMI and CRP was significantly stronger in females than males. Obese White females had mean CRP values slightly above 3 mg/liter (vs 2 for White males) and Black females had mean CRP values >4 mg/liter (vs 3 for Black males). More than 50% of Black females in the United States have obesity. Continued research into racial and sex differences in the relationship between obesity, inflammation, and health risks may ultimately lead to more personalized weight loss recommendations.
Obesity; C-reactive protein; Sex Differences; Race; Aged
Clinical decision support systems (CDSSs) can help clinicians assess cardiovascular disease (CVD) risk and manage CVD risk factors by providing tailored assessments and treatment recommendations based on individual patient data. The goal of this systematic review was to examine the effectiveness of CDSSs in improving screening for CVD risk factors, practices for CVD-related preventive care services such as clinical tests and prescribed treatments, and management of CVD risk factors.
An existing systematic review (search period, January 1975–January 2011) of CDSSs for any condition was initially identified. Studies of CDSSs that focused on CVD prevention in that review were combined with studies identified through an updated search (January 2011–October 2012). Data analysis was conducted in 2013.
A total of 45 studies qualified for inclusion in the review. Improvements were seen for recommended screening and other preventive care services completed by clinicians, recommended clinical tests completed by clinicians, and recommended treatments prescribed by clinicians (median increases of 3.8, 4.0, and 2.0 percentage points, respectively). Results were inconsistent for changes in CVD risk factors such as systolic and diastolic blood pressure, total and low-density lipoprotein cholesterol, and hemoglobin A1C levels.
CDSSs are effective in improving clinician practices related to screening and other preventive care services, clinical tests, and treatments. However, more evidence is needed from implementation of CDSSs within the broad context of comprehensive service delivery aimed at reducing CVD risk and CVD-related morbidity and mortality.
The challenges associated with developing more effective treatments for neurologic and psychiatric illness such as Alzheimer’s disease and schizophrenia are considerable. Both the symptoms and the pathophysiology of these conditions are complex and poorly understood and the clinical presentations across different patients can be very heterogeneous. Moreover, it has become apparent that the reductionist approach to drug discovery for these illnesses that has dominated the field for decades (i.e., the development of highly selective compounds or other treatment modalities focused on a very specific pathophysiologic target) has not been widely successful. Accordingly, a variety of new strategies have emerged including the development of “multitarget-directed ligands” (MTDLs), the development and/or identification of compounds that exhibit “multifunctional” activity (e.g., pro-cognitive plus neuroprotective, pro-cognitive plus antipsychotic activity), “repurposing” strategies for existing compounds that have other clinical indications, and novel “adjunctive” treatment strategies that might enhance the efficacy of the currently available treatments. Interestingly, a variety of ligands at nicotinic acetylcholine receptors (nAChRs) appear to have the potential to fulfill one or more of these desirable properties (i.e., multifunctional, repurposing, or adjunctive treatment potential). The purpose of this review (while not all-inclusive) is to provide an overview of a variety of nAChR ligands that demonstrate potential in these categories, particularly, “multifunctional” properties. Due to their densities in the mammalian brain and the amount of literature available, the review will focus on ligands of the high affinity α4β2 nAChR and affinity α7 nAChR.
Alzheimer’s disease; Mild Cognitive Impairment; Schizophrenia; Cholinergic; Memory
Students identified with learning disabilities experience markedly lower levels of science and mathematics achievement than students who are not identified with a learning disability. Seemingly compounding their disadvantage, students with learning disabilities also complete more credits in non-core coursework—traditionally considered non-academic coursework—than students who are not identified with a learning disability. The Education Longitudinal Study of 2002, a large national dataset with both regular and special education high school students, is utilized to determine whether credit accumulation in certain types of non-core coursework, such as Technology and Communications courses, is associated with improved science and math course-taking outcomes for students with learning disabilities. Results show that credit accumulation in Technology and Communications coursework uniquely benefits the science course-taking, and comparably benefits the math course-taking, of students identified with learning disabilities in contrast to students who are not identified with a learning disability.
Course-taking; vocational; career and technology education; elective; math; science; learning disabilities; high school; academic achievement
The antecedents of elevated blood pressure (BP) and its major consequences (cardiovascular disease and stroke) begin in childhood. Higher levels of BP early in life track into adulthood and are associated with subclinical target organ damage in children and adults. Diet behaviors, including the choice of high sodium containing foods, are established during childhood. On average, children, ages 2‐19, consume more than 3,100 mg of sodium per day, with substantially greater sodium intakes in boys than girls. Importantly, studies show that lowering sodium intake in children lowers blood pressure. In view of this evidence, US Dietary Guidelines recommend a reduced sodium intake in children. Current federal nutrition standards include a step‐wise reduction in the sodium levels of school meals. The ultimate goal is to help children achieve daily sodium intakes that do not exceed upper levels recommended by the Institute of Medicine and the Dietary Guidelines for Americans. In summary, available data are sufficiently strong to recommend a lower sodium intake beginning in early in life as an effective and well‐tolerated approach to reducing BP in children. Current efforts to weaken nutrition standards for school meals undermine an effective strategy aimed at improving the health of our children and our nation.