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A classic body-composition method is estimation of total-body skeletal muscle mass (SM, in kg) from 24-h urinary creatinine excretion (in g). Two approaches of unknown validity have been used to calculate SM from creatinine: one assumes a constant ratio of SM to creatinine, the so-called creatinine equivalence (k), and that SM = k X creatinine; the other suggests a highly variable ratio of SM to creatinine and is based on regression equations of the form SM = b + a X creatinine. We explored these two extreme possibilities by measuring SM with whole-body computerized axial tomography and collecting urinary creatinine during meat-free dietary conditions in 12 healthy adult men. Prediction equations were developed in the men that fit these two models: SM = 21.8 X creatinine (SD and CV of the ratio of SM to creatinine: 1.3 kg and 6.0%, respectively) and SM = 18.9 X creatinine + 4.1 (r = 0.92, P = 2.55 X l0(-5), SEE = 1.89 kg). The validity of each model is reviewed in the context of theoretical aspects of creatine-creatinine metabolism. This first investigation of the method of measuring urinary creatinine excretion to determine SM by using modern techniques raises important practical and basic questions related to SM prediction. [ABSTRACT FROM AUTHOR]

Abstract Background The purpose of the study is to describe the impact of oral health-related quality of life (OHRQoL) on the lives of pre-seniors and seniors living in Nova Scotia, Canada. Methods This cross-sectional study involved 1461 participants, grouped by age (pre-seniors [45–64] and seniors [65+]) and residential status (long-term care facility [LTC] or community). OHRQoL was measured using the 14-item Oral Health Impact Profile questionnaire (OHIP-14) in a random digit dialing telephone survey (for community residents) or a face-to-face interview (for LTC residents). Intra-oral examinations were performed by one of six dentists calibrated to W.H.O. standards. Results Approximately one in four pre-seniors and seniors reported at least one OHRQoL impact ‘fairly/very often’. The most commonly reported impacts were within the dimensions ‘physical pain’ and ‘psychological discomfort’. It was found that 12.2% of LTC residents found it uncomfortable to eat any foods ‘fairly/very’ often compared to 7.7% in the community, and 11.6% of LTC residents reported being self-conscious ‘fairly/very often’ compared to 8.2% in the community. Of those residing in the community, pre-seniors (28.8%) reported significantly more impacts than seniors (22.0%); but there were no significant differences in OHRQoL between pre-seniors (21.2%) and seniors (25.3%) in LTC. Pre-seniors living in the community scored significantly higher than community dwelling seniors on prevalence, extent and severity of OHIP-14 scores. Logistic regression revealed that for the community dwelling sample, individuals living in rural areas in addition to those being born outside of Canada were approximately 2.0 times more likely to report an impact ‘fairly/very often’, whereas among the LTC sample, those having a high school education or less were 2.3 times more likely to report an impact. Conclusions Findings indicate that the oral health and OHRQoL of both pre-seniors and seniors in LTC residents is poor. Community dwelling pre-seniors have the highest prevalence rate of oral impacts.

Abstract Background Vascular stents are small tubular scaffolds used in the treatment of arterial stenosis (narrowing of the vessel). Most vascular stents are metallic and are deployed either by balloon expansion or by self-expansion. A shape memory polymer (SMP) stent may enhance flexibility, compliance, and drug elution compared to its current metallic counterparts. The purpose of this study was to describe the fabrication of a laser-activated SMP stent and demonstrate photothermal expansion of the stent in an in vitro artery model. Methods A novel SMP stent was fabricated from thermoplastic polyurethane. A solid SMP tube formed by dip coating a stainless steel pin was laser-etched to create the mesh pattern of the finished stent. The stent was crimped over a fiber-optic cylindrical light diffuser coupled to an infrared diode laser. Photothermal actuation of the stent was performed in a water-filled mock artery. Results At a physiological flow rate, the stent did not fully expand at the maximum laser power (8.6 W) due to convective cooling. However, under zero flow, simulating the technique of endovascular flow occlusion, complete laser actuation was achieved in the mock artery at a laser power of ~8 W. Conclusion We have shown the design and fabrication of an SMP stent and a means of light delivery for photothermal actuation. Though further studies are required to optimize the device and assess thermal tissue damage, photothermal actuation of the SMP stent was demonstrated.

Background and Purpose: Near-peer teaching is an innovative approach to teaching the skills of supervising and precepting while benefiting students with different levels of experience and academic training. This study describes near-peer activities in skills-based laboratory courses that provided opportunities for one-on-one teaching to benefit learners in the introductory lab courses while simultaneously training more advanced students for future supervisory and precepting roles., Educational Activity & Setting: Three community pharmacy near-peer teaching simulations were designed and implemented: 1) Patient Counseling and Medication Adherence, 2) Dispensing and Patient Counseling, and 3) Drug Utilization Review and Prescriber Calls. These activities took place over two semesters of a pharmacy skills lab with all first- and third-year Doctor of Pharmacy students., Findings: In Autumn 2019, 80% (111/139) of P1s and 67% (80/119) of P3s responded to the course evaluation survey. In Spring 2020, 73% (100/137) of P1s and 68% (80/118) of P3s responded to the course evaluation survey. The P3s reported increased confidence in their ability to provide meaningful feedback, while P1s reported increased confidence in communicating with patients and healthcare providers. Performance data revealed that most P1s and P3s completed dispensing and communication activities accurately using a near-peer approach. Overall, the P1s and P3s felt the activities were valuable learning experiences., Summary: The near-peer activities described in this study fill a gap in the training of pharmacy graduates for future precepting and supervisory roles. Evaluation of these near-peer activities suggest that both junior and senior learners benefit from simulated preceptor-intern interactions, supporting this innovative approach to address supervisory and precepting responsibilities., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective : It is unknown whether the relative contribution to energy imbalance in amyotrophic lateral sclerosis (ALS) is due to decreased energy intake, or increased energy expenditure from hyper-metabolism and/or physical activity, or both. Methods : We studied 10 free-living sporadic ALS subjects with mild to moderate disease and 10 matched healthy controls to address this question. We estimated energy intake by 24-h recall in ALS subjects and three-day food diary in all. We estimated body composition by dual energy X-ray absorptiometry and resting metabolic rate by indirect calorimetry; and measured total daily energy expenditure (TEE) and physical activity-energy expenditure using doubly labeled water. Results : Daily energy intake was no different between ALS subjects and controls. Despite lower fat-free mass, unadjusted TEE was higher in ALS subjects than controls (2844 ± 319 vs. 2505 ± 261 kcal/d, p  = 0.005 by paired t -test). Compared to controls, hyper-metabolism occurred in 80% of ALS subjects. Physical activity-energy expenditure was higher in ALS subjects than controls (718 ± 262 kcal/d vs. 487 ± 196 kcal/d, p  = 0.04). In controls, energy intake matched TEE; in ALS subjects TEE was higher than energy intake. Conclusions : We found higher TEE in ALS subjects than controls, with larger contribution to difference from physical activity-energy expenditure than hyper-metabolism. Although daily energy intake in ALS subjects was similar to that in controls, they were unable to compensate for increased energy needs. To accurately determine energy balance and optimize nutrition in ALS, future studies should consider measuring energy intake, energy expenditure, and physical activity.

Introduction:  Total knee arthroplasty (TKA) is now being performed in the outpatient setting, and often the postoperative pain is managed with opioid analgesics. Non-opioid pain management modalities are in crucial demand, and we propose a surgical technique that can potentially result in less pain and the decrease in the use of opioid analgesia following TKA. The purpose of this study was to investigate the safety and efficacy of a novel peripheral nerve block (PNB) that includes a single injection and catheter placement for a continuous regional nerve block in total knee arthroplasty., Methods:  Fifty-six patients underwent TKA by a single surgeon utilizing the novel method. Patient-reported outcomes were entered into an outcomes database and compared to an aggregate of over 3,500 comparative TKA patients. A visual analog scale (VAS) evaluated perioperative pain. Patient perioperative opioid usage, expectations of pain control, the incidence of common side effects, and the average hospital length of stay (LOS) were collected., Results:  Compared to the aggregate of patients in the database, the patients who received the novel surgeon-placed adductor canal block (ACB) and catheter placement reported findings that suggest this technique can possibly lead to a decrease in the severity of pain in addition to a reduction in side effects and the need for opioid analgesia. LOS for these patients was short, and patient satisfaction scores were excellent for the surgeon performing this technique., Conclusions: Using the placement technique described, surgeons can reproducibly perform a single injection of PNB and place an indwelling catheter in the adductor canal through direct visualization of the muscles that make up the borders of the adductor canal. This technique offers potential advantages over pain management modalities that can be elucidated in further studies. The power of this study is limited due to these findings having not been analyzed for statistical significance., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Matthews et al.)

Objective. To determine the impact of the holistic redesign of top 200 medications learning activities within a Doctor of Pharmacy (PharmD) curriculum by comparing student performances on a comprehensive examination before and after the redesign. Methods. During a curricular revision at The Ohio State University College of Pharmacy that began with the class of 2020, learning activities involving the top 200 medications were implemented that involved repeated retrieval and mastery concepts, alignment with therapeutic coursework, and autonomous learning regarding the top 200 medications. A high-stakes comprehensive top 200 medications examination was administered to students at the end of their third professional year both before and after implementation of these activities. The difference in the percentage of students who achieved a satisfactory score on the comprehensive examination was compared between cohorts prior to and following the curricular redesign. Results. The study analyzed results from 134, 130, and 120 students from three PharmD classes (one before and two after the redesign of top 200 medications activities). Following the redesign, a higher percentage of students achieved a satisfactory score of 85% on the examination (class of 2020: 116/130, 89.2%; class of 2022: 107/120, 89.2%) compared to before the redesign (class of 2019: 88/134, 65.7%). Conclusion. The combination of repeated retrieval and mastery, alignment with therapeutic coursework, and development of autonomous learning can significantly increase student knowledge and retention of top 200 medications., (© 2023 American Association of Colleges of Pharmacy.)

Objectives: Treatment of opioid use disorder with methadone is highly effective. Methadone is dispensed from opioid treatment programs under regulated circumstances. However, diversion of take-home doses can occur and is difficult to detect. We wanted to test the application of a handheld ultraviolet light absorption spectrometer to detect the concentration of methadone in take-home bottles that were suspected of being altered by the patient., Methods: Standardized dilutions of methadone hydrochloride oral concentrate were used to calibrate absorption wavelengths and then compared to take homes from suspected and unsuspected bottles to see if measured concentrations differed from expected doses., Results: Ten standardized "control" doses were analyzed to determine 99% confidence intervals. These were compared to 104 samples "not-of-concern" obtained randomly over a 10-month period. An additional 103 methadone bottles of concern from 27 patients showed 15 bottles with <25 % and 8 with <75 % of expected concentrations., Conclusions: A handheld, low-cost ultraviolet light spectrometer detected altered take-home doses of methadone. This assay presents a simple and effective method for methadone clinics to perform inhouse analysis on "call back" methadone doses. It allows individual clinics to define diversion rates of their patient body, while allowing state and federal agencies to better understand how much prescribed methadone is diverted for illicit uses., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Objective. To evaluate the interrater reliability of a universal evaluator rubric used to assess student pharmacist communication skills during patient education sessions. Methods. Six US schools and colleges of pharmacy each submitted 10 student videos of a simulated community pharmacy patient education session and recruited two raters in each of the five rater groups (faculty, standardized patients, postgraduate year one residents, student pharmacists, and pharmacy preceptors). Raters used a rubric containing 20 items and a global assessment to evaluate student communication of 12 videos. Agreement was computed for individual items and overall rubric score within each rater group, and for each item across all rater groups. Average overall rubric agreement scores were compared between rater groups. Agreement coefficient scores were categorized as no to minimal, weak, moderate, strong, or almost perfect agreement. Results. Fifty-five raters representing five rater groups and six pharmacy schools evaluated student communication. Item agreement analysis for all raters revealed five items with no to minimal or weak agreement, 10 items with moderate agreement, one item with strong agreement, and five items with almost perfect agreement. Overall average agreement across all rater groups was 0.73 (95% CI, 0.66-0.81). The preceptor rater group exhibited the lowest agreement score of 0.68 (95% CI, 0.58-0.78), which significantly deviated from the overall average. Conclusion. While strong or almost perfect agreement scores were not observed for all rubric items, overall average interrater reliability results support the use of this rubric in a variety of raters to assess student pharmacist communication skills during patient education sessions., (© 2022 American Association of Colleges of Pharmacy.)

Cells regulate their cell volume, but cell volumes may change in response to metabolic and other perturbations. Many metabolomics experiments use cultured cells to measure changes in metabolites in response to physiological and other experimental perturbations, but the metabolomics workflow by mass spectrometry only determines total metabolite amounts in cell culture extracts. To convert metabolite amount to metabolite concentration requires knowledge of the number and volume of the cells. Measuring only metabolite amount can lead to incorrect or skewed results in cell culture experiments because cell size may change due to experimental conditions independent of change in metabolite concentration. We have developed a novel method to determine cell volume in cell culture experiments using a pair of stable isotopically labeled phenylalanine internal standards incorporated within the normal liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics workflow. This method relies on the flooding-dose technique where the intracellular concentration of a particular compound (in this case phenylalanine) is forced to equal its extracellular concentration. We illustrate the LC-MS/MS technique for two different mammalian cell lines. Although the method is applicable in general for determining cell volume, the major advantage of the method is its seamless incorporation within the normal metabolomics workflow.

When students fail to meet minimum competence standards on summative pharmacy skills-based assessments, remediation can be used to ensure student readiness for progression. Skills-based remediation is challenging as a high volume of resources is required to develop an action plan that addresses the heterogeneity in student needs and to create and execute another assessment equivalent to the initial assessment. Although many Doctor of Pharmacy (PharmD) programs face these same challenges, there is no consensus on how to best address them. Recently, faculty from six PharmD programs convened to share ideas and approaches to overcoming these challenges. This commentary aims to define remediation as it pertains to summative skills-based assessments, share our consensus views regarding remediation best practices, and highlight areas where there is more work to be done. Our intent is to advance the ongoing conversation and empower institutions to develop their own effective and impactful skills-based remediation policies, procedures, and activities., (© 2021 American Association of Colleges of Pharmacy.)

Objective. To assess the impact of the Patient Voices series on Doctor of Pharmacy (PharmD) students. Methods. A series of patient speakers and integrated simulation activities focused on underserved populations, otherwise known as the Patient Voices series, was embedded into a pharmacy skills laboratory curriculum. First-year PharmD students' self-ratings of confidence were compared on pre- and post-course surveys. Using evaluations from first-year introductory pharmacy practice experiences (IPPEs), student self-evaluation data were compared to preceptor evaluations of student performance. Open-ended responses to course evaluations from first- and second-year PharmD students and student reflections from third-year PharmD students were assessed using conventional content analysis to identify and characterize student perceptions. Results. Significant increases were observed in first-year students' confidence to show empathy (mean, 4.2 to 4.7) and to interact with patients from underserved communities (mean, 2.2 to 4.2). Preceptor ratings of students' empathy were consistent with the students' self-rated abilities, while students' self-ratings on cultural sensitivity were higher than the preceptors' ratings. Qualitative analysis of course evaluation surveys and reflections revealed common themes identified by students, such as understanding different perspectives, increased empathy for patients, and the value of including this content in the curriculum. Conclusion. Student confidence to interact with patients from a variety of underserved populations increased following introduction of the Patient Voices series into the PharmD curriculum. Students perceived the series to be a valuable learning experience., (© 2021 American Association of Colleges of Pharmacy.)

Chemotherapy remains the standard of care for most cancers worldwide, however development of chemoresistance due to the presence of the drug-effluxing ATP binding cassette (ABC) transporters remains a significant problem. The development of safe and effective means to overcome chemoresistance is critical for achieving durable remissions in many cancer patients. We have investigated the energetic demands of ABC transporters in the context of the metabolic adaptations of chemoresistant cancer cells. Here we show that ABC transporters use mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer cells. We further demonstrate that the loss of methylation-controlled J protein (MCJ) (also named DnaJC15), an endogenous negative regulator of mitochondrial respiration, in chemoresistant cancer cells boosts their ability to produce ATP from mitochondria and fuel ABC transporters. We have developed MCJ mimetics that can attenuate mitochondrial respiration and safely overcome chemoresistance in vitro and in vivo. Administration of MCJ mimetics in combination with standard chemotherapeutic drugs could therefore become an alternative strategy for treatment of multiple cancers.

Peptide identification by liquid chromatography-mass spectrometry (LC-MS) requires retention and elution of peptides from the LC column. Although medium and hydrophobic peptides are readily retained by the C18 columns that are commonly used in proteomics, short and hydrophilic peptides are not retained nor measured by MS due to their elution in the void volume after sample injection. These nonretained peptides can possess important post-translational modifications, such as glycosylation or phosphorylation. We describe a total retention LC-MS method that employs a reverse phase C18 column and porous graphitic carbon (PGC) column to retain both hydrophobic and hydrophilic peptides for LC-MS analysis. Our setup uses a single valve with a trapping column and two LC pumps run at low microliter/minute flow rates to deliver separate gradients to parallel capillary C18 and PGC columns. Our capillary LC system balances the need for high sensitivity with ease of implementation as compared to other 2D LC systems that use nanocolumns with multiple trapping columns and multiport valves. We demonstrate the utility of the method identifying hydrophilic peptides that went undetected when only a C18 nanocolumn was used. These missed hydrophilic peptides include tripeptides and N-glycosylated species.

Growing evidence demonstrates that human mesenchymal stromal cells (MSCs) modify their in vivo anti-inflammatory actions depending on the specific inflammatory environment encountered. Understanding this better is crucial to refine MSC-based cell therapies for lung and other diseases. Using acute exacerbations of cystic fibrosis (CF) lung disease as a model, the effects of ex vivo MSC exposure to clinical bronchoalveolar lavage fluid (BALF) samples, as a surrogate for the in vivo clinical lung environment, on MSC viability, gene expression, secreted cytokines, and mitochondrial function were compared with effects of BALF collected from healthy volunteers. CF BALF samples that cultured positive for Aspergillus sp. (Asp) induced rapid MSC death, usually within several hours of exposure. Further analyses suggested the fungal toxin gliotoxin as a potential mediator contributing to CF BALF-induced MSC death. RNA sequencing analyses of MSCs exposed to either Asp+ or Asp- CF BALF samples identified a number of differentially expressed transcripts, including those involved in interferon signaling, antimicrobial gene expression, and cell death. Toxicity did not correlate with bacterial lung infections. These results suggest that the potential use of MSC-based cell therapies for CF or other lung diseases may not be warranted in the presence of Aspergillus .

Lysine cannot be synthesized by most higher organisms and, therefore, is an indispensable amino acid (IAA) that must be consumed in adequate amounts to maintain protein synthesis. Although lysine is an abundant amino acid in body proteins, lysine is limited in abundance in many important food sources (e.g. grains). Older observations assigned importance to lysine because animals fed a lysine-deficient diet did not lose weight as fast as animals placed upon other IAA-deficient diets, leading to the theory that there may be a special pool of lysine or metabolites that could be converted to lysine. The first step in the lysine catabolic pathway is the formation of saccharopine and then 2-aminoadipic acid, processes that are mitochondrial. The catabolism of 2-aminoadipic acid proceeds via decarboxylation to a series of CoA esters ending in acetyl-CoA. In mammals, the liver appears to be the primary site of lysine catabolism. In humans, the metabolic and oxidative response of lysine to diets either restricted in protein or in lysine is consistent with what has been measured for other IAAs with isotopically labeled tracers. Intestinal microflora are known to metabolize urea to ammonia and scavenge nitrogen (N) for the synthesis of amino acids. Studies feeding 15N-ammonium chloride or 15N-urea to animals and to humans, demonstrate the appearance of 15N-lysine in gut microbial lysine and in host lysine. However, the amount of 15N-lysine transferred to the host is difficult to assess directly using current methods. It is important to understand the role of the gut microflora in human lysine metabolism, especially in conditions where dietary lysine intake may be limited, but better methods need to be devised., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

GrainGenes (https://wheat.pw.usda.gov or https://graingenes.org) is an international centralized repository for curated, peer-reviewed datasets useful to researchers working on wheat, barley, rye and oat. GrainGenes manages genomic, genetic, germplasm and phenotypic datasets through a dynamically generated web interface for facilitated data discovery. Since 1992, GrainGenes has served geneticists and breeders in both the public and private sectors on six continents. Recently, several new datasets were curated into the database along with new tools for analysis. The GrainGenes homepage was enhanced by making it more visually intuitive and by adding links to commonly used pages. Several genome assemblies and genomic tracks are displayed through the genome browsers at GrainGenes, including the Triticum aestivum (bread wheat) cv. 'Chinese Spring' IWGSC RefSeq v1.0 genome assembly, the Aegilops tauschii (D genome progenitor) Aet v4.0 genome assembly, the Triticum turgidum ssp. dicoccoides (wild emmer wheat) cv. 'Zavitan' WEWSeq v.1.0 genome assembly, a T. aestivum (bread wheat) pangenome, the Hordeum vulgare (barley) cv. 'Morex' IBSC genome assembly, the Secale cereale (rye) select 'Lo7' assembly, a partial hexaploid Avena sativa (oat) assembly and the Triticum durum cv. 'Svevo' (durum wheat) RefSeq Release 1.0 assembly. New genetic maps and markers were added and can be displayed through CMAP. Quantitative trait loci, genetic maps and genes from the Wheat Gene Catalogue are indexed and linked through the Wheat Information System (WheatIS) portal. Training videos were created to help users query and reach the data they need. GSP (Genome Specific Primers) and PIECE2 (Plant Intron Exon Comparison and Evolution) tools were implemented and are available to use. As more small grains reference sequences become available, GrainGenes will play an increasingly vital role in helping researchers improve crops., (Published by Oxford University Press 2019.)

The type I cGMP-dependent protein kinases (PKG I) serve essential physiological functions, including smooth muscle relaxation, cardiac remodeling, and platelet aggregation. These enzymes form homodimers through their N-terminal dimerization domains, a feature implicated in regulating their cooperative activation. Previous investigations into the activation mechanisms of PKG I isoforms have been largely influenced by structures of the cAMP-dependent protein kinase (PKA). Here, we examined PKG Iα activation by cGMP and cAMP by engineering a monomeric form that lacks N-terminal residues 1-53 (Δ53). We found that the construct exists as a monomer as assessed by whole-protein MS, size-exclusion chromatography, and small-angle X-ray scattering (SAXS). Reconstruction of the SAXS 3D envelope indicates that Δ53 has a similar shape to the heterodimeric RIα-C complex of PKA. Moreover, we found that the Δ53 construct is autoinhibited in its cGMP-free state and can bind to and be activated by cGMP in a manner similar to full-length PKG Iα as assessed by surface plasmon resonance (SPR) spectroscopy. However, we found that the Δ53 variant does not exhibit cooperative activation, and its cyclic nucleotide selectivity is diminished. These findings support a model in which, despite structural similarities, PKG Iα activation is distinct from that of PKA, and its cooperativity is driven by in trans interactions between protomers., (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)

We present a study of hydration in ALS patients and its effects on survival. This was a multicenter study over 48 weeks in 80 ALS patients who underwent 250 individual measurements using doubly labeled water (DLW). Total body water (TBW) and water turnover (a surrogate for water intake) were 3.4% and 8.6% lower, respectively, in patients compared to age- and gender-matched healthy controls, and both significantly decreased over study duration. In 20% of patients, water turnover measured over 10 d was 2 standard deviations below the mean value in healthy controls. In a separate clinic cohort of 208 patients, water intake estimated from a de novo equation created from common clinical endpoints was a prognostic indicator of survival. Regardless of nutritional state assessed by BMI, survival was two-fold longer in the group above the median for estimated water intake, suggesting that hydration may be a more important predictor of survival than malnutrition. Risk factors for poor hydration were identified. Water intake equations recommended by US Centers for Medicare and Medicaid Services in healthy elderly were inaccurate for use in ALS patients. We developed equations to estimate TBW and water intake in ALS patients for use in clinics to accurately estimate hydration and improve clinical care.

Background: Population health management uses proactive, targeted interventions to improve health outcomes., Objectives: To compare the effectiveness of and time required for 2 pharmacist-driven population health management interventions to improve vitamin B12 monitoring in patients taking metformin., Methods: Physicians were randomized to 1 of 2 population health management interventions. For all patients of physicians assigned to the patient portal intervention, a pharmacist communicated need for vitamin B12 monitoring directly to the patient using an electronic patient portal. For all patients of physicians assigned to the office visit intervention, a pharmacist communicated monitoring recommendations to the physician prior to a scheduled office visit through the electronic health record. The proportion of patients in each group who received vitamin B12 monitoring 30 days after the intervention was quantified., Results: A total of 489 patients of 26 physicians within 5 general internal medicine clinics who had taken metformin for at least 1 year and had not received vitamin B12 monitoring within the past year were identified. The intervention delivered as part of an office visit resulted in increased serum vitamin B12 monitoring compared with the intervention using electronic communication through a patient portal (odds ratio = 4.05; 95% CI = 1.22, 13.46; P = 0.03). The office visit intervention and the patient portal intervention took an average of 8.2 and 0.9 minutes per patient, respectively., Conclusions: Population health management completed during the course of office visits was more effective at increasing vitamin B12 monitoring and required more time than an intervention delivered through an electronic patient portal., (© The Author(s) 2016.)

Nitrogen dioxide (NO2) is an environmental air pollutant and endogenously generated oxidant that contributes to the exacerbation of respiratory disease and can function as an adjuvant to allergically sensitize to an innocuous inhaled Ag. Because uric acid has been implicated as a mediator of adjuvant activity, we sought to determine whether uric acid was elevated and participated in a mouse model of NO2-promoted allergic sensitization. We found that uric acid was increased in the airways of mice exposed to NO2 and that administration of uricase inhibited the development of OVA-driven allergic airway disease subsequent to OVA challenge, as well as the generation of OVA-specific Abs. However, uricase was itself immunogenic, inducing a uricase-specific adaptive immune response that occurred even when the enzymatic activity of uricase had been inactivated. Inhibition of the OVA-specific response was not due to the capacity of uricase to inhibit the early steps of OVA uptake or processing and presentation by dendritic cells, but occurred at a later step that blocked OVA-specific CD4(+) T cell proliferation and cytokine production. Although blocking uric acid formation by allopurinol did not affect outcomes, administration of ultra-clean human serum albumin at protein concentrations equivalent to that of uricase inhibited NO2-promoted allergic airway disease. These results indicate that, although uric acid levels are elevated in the airways of NO2-exposed mice, the powerful inhibitory effect of uricase administration on allergic sensitization is mediated more through Ag-specific immune deviation than via suppression of allergic sensitization, a mechanism to be considered in the interpretation of results from other experimental systems., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2016 by The American Association of Immunologists, Inc.)

The Triticeae Toolbox (; T3) is the database schema enabling plant breeders and researchers to combine, visualize, and interrogate the wealth of phenotype and genotype data generated by the Triticeae Coordinated Agricultural Project (TCAP). T3 enables users to define specific data sets for download in formats compatible with the external tools TASSEL, Flapjack, and R; or to use by software residing on the T3 server for operations such as Genome Wide Association and Genomic Prediction. New T3 tools to assist plant breeders include a Selection Index Generator, analytical tools to compare phenotype trials using common or user-defined indices, and a histogram generator for nursery reports, with applications using the Android OS, and a Field Plot Layout Designer in development. Researchers using T3 will soon enjoy the ability to design training sets, define core germplasm sets, and perform multivariate analysis. An increased collaboration with GrainGenes and integration with the small grains reference sequence resources will place T3 in a pivotal role for on-the-fly data analysis, with instant access to the knowledge databases for wheat and barley. T3 software is available under the GNU General Public License and is freely downloadable., (Copyright © 2016 Crop Science Society of America.)

We recently reported that lowering the high, habitual palmitic acid (PA) intake in ovulating women improved insulin sensitivity and both inflammatory and oxidative stress. In vitro studies indicate that PA can activate both cell membrane toll-like receptor-4 and the intracellular nucleotide oligomerization domain-like receptor protein (NLRP3). To gain further insight into the relevance to human metabolic disease of dietary PA, we studied healthy, lean and obese adults enrolled in a randomized, crossover trial comparing 3-week, high-PA (HPA) and low-PA/high-oleic-acid (HOA) diets. After each diet, both hepatic and peripheral insulin sensitivities were measured, and we assessed cytokine concentrations in plasma and in supernatants derived from lipopolysaccharide-stimulated peripheral blood mononuclear cells (PBMCs) as well as proinflammatory gene expression in skeletal muscle. Insulin sensitivity was unaffected by diet. Plasma concentration of tumor necrosis factor-α was higher during the HPA diet. Lowering the habitually high PA intake by feeding the HOA diet resulted in lower secretion of interleukin (IL)-1β, IL-18, IL-10, and tumor necrosis factor-α by PBMCs, as well as lower relative mRNA expression of cJun and NLRP3 in muscle. Principal components analysis of 156 total variables coupled to analysis of covariance indicated that the mechanistic pathway for the differential dietary effects on PBMCs involved changes in the PA/OA ratio of tissue lipids. Our results indicate that lowering the dietary and tissue lipid PA/OA ratio resulted in lower leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes, but the relevance to diabetes risk is uncertain., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Palmitic acid (PA) is associated with higher blood concentrations of medium-chain acylcarnitines (MCACs), and we hypothesized that PA may inhibit progression of FA β-oxidation. Using a cross-over design, 17 adults were fed high PA (HPA) and low PA/high oleic acid (HOA) diets, each for 3 weeks. The [1-(13)C]PA and [13-(13)C]PA tracers were administered with food in random order with each diet, and we assessed PA oxidation (PA OX) and serum AC concentration to determine whether a higher PA intake promoted incomplete PA OX. Dietary PA was completely oxidized during the HOA diet, but only about 40% was oxidized during the HPA diet. The [13-(13)C]PA/[1-(13)C]PA ratio of PA OX had an approximate value of 1.0 for either diet, but the ratio of the serum concentrations of MCACs to long-chain ACs (LCACs) was significantly higher during the HPA diet. Thus, direct measurement of PA OX did not confirm that the HPA diet caused incomplete PA OX, despite the modest, but statistically significant, increase in the ratio of MCACs to LCACs in blood., (Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.)

We propose graphical diagnostic tools to assess the fit of a bivariate accelerated lifetime regression model. Using univariate residuals for each response measurement in a pair, we assess their dependence structure via the bivariate probability integral transformation of univariate residuals, which we call V-residuals. To reduce the computational burden associated with plots of V-residuals, as well as some uncertainty associated with parameter estimation, we next develop K-residuals. We also devise adjusted V- and K-residuals to account for right censoring of any response. Via simulation studies, we examine the statistical behaviour of Q-Q plots of the estimated K-residuals, and demonstrate the potential of these plots to identify an appropriate choice of frailty distribution in bivariate modeling. We apply our proposed diagnostic tools to the Diabetic Retinopathy Study and assess the goodness of fit of various models fitted to these study data using different choices of frailty distributions combined with several baseline survivor functions.

Our objective was to explore if creatine kinase (CK) levels correlate with survival in amyotrophic lateral sclerosis (ALS), and whether a correlation is independent of other well-studied predictors such as location of onset, gender, age, fat free mass, spasticity, cramps, and fasciculations. We analyzed data from 80 ALS patients from a 48-week non-interventional longitudinal multicenter nutrition study with long term follow-up. The overall mean CK was 214 ± 191.8 U/l (range 22-1992 U/l). Forty-five percent of patients had at least one high CK value (> 200 U/l), and about half maintained a high CK value, but there was no trend over the study period. Male gender and extremity onset were significantly associated with high CK. In univariate analysis, age, bioelectric impedance spectroscopy (BIS) fat free mass, spasticity, and fasciculations were not associated with CK level. There was an association between CK and muscle cramps (p < 0.001). In survival analysis, low CK (≤ 200 U/l) was associated with a longer overall survival (p = 0.02), when adjusting for location of onset, age, race, gender, BIS fat free mass, and study site. In conclusion, CK may be a useful marker for ALS survival, which has implications for clinical care and the design of future clinical trials.

Background: Patients with amyotrophic lateral sclerosis (ALS) experience progressive limb weakness, muscle atrophy, and dysphagia, making them vulnerable to insufficient energy intake. Methods to estimate energy requirements have not been devised for this patient group., Objective: The goal was to develop equations to estimate energy requirements of ALS patients., Design: We enrolled 80 ALS participants at varying stages of their illness and studied them every 16 wk over 48 wk. At each time, we determined total daily energy expenditure (TDEE) in the home setting over a 10-d period by using the doubly labeled water method. We then developed statistical models to estimate TDEE by using factors easily obtained during a routine clinical visit., Results: The most practical TDEE models used the Harris-Benedict, Mifflin-St Jeor, or Owen equations to estimate resting metabolic rate (RMR) and 6 questions from the revised ALS Functional Rating Scale (ALSFRS-R) that relate to physical activity. We developed a Web-based calculator to facilitate its use. In the research setting, measuring body composition with bioelectrical impedance spectroscopy enabled the estimation of RMR with the Rosenbaum equation and the same 6 questions from the ALSFRS-R to estimate TDEE. By using these models, the estimate of TDEE for nutritional maintenance was ±500 kcal/d across the spectrum of ALS progression., Conclusions: Our results emphasize the importance of physical function and body composition in estimating TDEE. Our predictive equations can serve as a basis for recommending placement of a feeding gastrostomy in ALS patients who fail to meet their energy requirements by oral intake.

Background: Tissue factor (TF), an in vivo initiator of blood coagulation, is a transmembrane protein and has two disulfides in the extracellular domain. The integrity of one cysteine pair, Cys186-Cys209, has been hypothesized to be essential for an allosteric "decryption" phenomenon, presumably regulating TF procoagulant function, which has been the subject of a lengthy debate. The conclusions of published studies on this subject are based on indirect evidences obtained by the use of reagents with potentially oxidizing/reducing properties., Methods: The status of disulfides in recombinant TF1-263 and natural placental TF in their non-reduced native and reduced forms was determined by mass-spectrometry. Functional assays were performed to assess TF cofactor function., Results: In native proteins, all four cysteines of the extracellular domain of TF are oxidized. Reduced TF retains factor VIIa binding capacity but completely loses the cofactor function., Conclusion: The reduction of TF disulfides (with or without alkylation) eliminates TF regulation of factor VIIa catalytic function in both membrane dependent FX activation and membrane independent synthetic substrate hydrolysis., General Significance: Results of this study advance our knowledge on TF structure/function relationships., (Copyright © 2013 Elsevier B.V. All rights reserved.)