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Although previous studies described the production of IgG antibodies in a subgroup of patients with common variable immunodeficiency (CVID) following messenger RNA vaccinations with BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (CVID responders), the functionality of these antibodies in terms of avidity as measured by the dissociation rate constant (k dis) and the antibody response to booster immunization has not been studied. We sought to analyze in CVID responders and healthy individuals, the avidity of anti–SARS-CoV-2 serum antibodies and their neutralization capacity as measured by surrogate virus–neutralizing antibodies in addition to IgG-, IgM-, and IgA-antibody levels and the response of circulating (peripheral blood) follicular T-helper cells after a third vaccination with BNT162b2 SARS-CoV-2 messenger RNA vaccine. Binding IgG, IgA, and IgM serum levels were analyzed by ELISA in patients with CVID responding to the primary vaccination (CVID responders, n = 10) and healthy controls (n = 41). The binding avidity of anti–spike antibodies was investigated using biolayer interferometry in combination with biotin-labeled receptor-binding-domain of SARS-CoV-2 spike protein and streptavidin-labeled sensors. Antigen-specific recall T-cell responses were assessed by measuring activation-induced markers by flow cytometry. After the third vaccination with BNT162b2, IgG-, IgM-, and IgA-antibody levels, surrogate virus–neutralizing antibody levels, and antibody avidity were lower in CVID responders than in healthy controls. In contrast, anti–SARS-CoV-2 spike protein avidity was comparable in CVID responders and healthy individuals following primary vaccination. Follicular T-helper cell response to booster vaccination in CVID responders was significantly reduced when compared with that in healthy individuals. Impaired affinity maturation during booster response provides new insight into CVID pathophysiology. [ABSTRACT FROM AUTHOR]

Accurate methods of identifying patients with suboptimal adherence to cardiometabolic medications are needed, and each approach has benefits and tradeoffs. We used data from a large trial of patients with poorly controlled cardiometabolic disease and evidence of medication non-adherence measured using pharmacy claims data whose adherence was subsequently assessed during a telephone consultation with a clinical pharmacist. We then evaluated if the pharmacist assessment agreed with the non-adherence measured using claims. When pharmacist and claims assessments disagreed, we identified reasons why claims were insufficient and used multivariable modified Poisson regression to identify patient characteristics associated with disagreement. Of 1,069 patients identified as non-adherent using claims (proportion of days covered [PDC] <80%), 646 (60.4%) were confirmed as non-adherent on pharmacist interview. For the 423 patients (39.6%) where the interview disagreed with the claims, the most common reasons were paying cash or using an alternate insurance (36.6%), medication discontinuation or regimen change (32.8%), and recently becoming adherent (26.7%). Compared to patients whose claims and interview both showed non-adherence, patients whose interview disagreed with claims were less likely to miss outpatient office visits (RR:0.91, 95%CI:0.85-0.97) and more likely to have a baseline PDC above the median (RR:1.35, 95%CI:1.10-1.64). Among patients identified as non-adherent by claims, 39.6% were observed to be adherent when assessed during pharmacist consultation. This discrepancy was largely driven by paying out-of-pocket, using alternative insurance, or medication discontinuation or change. These findings have important implications for using pharmacy claims to identify and intervene upon medication non-adherence. [ABSTRACT FROM AUTHOR]

Patient reports of moderate to severe pain are common across the spectrum of chronic kidney disease. The synergistic effects of comorbid depression and anxiety can lead to maladaptive coping responses to pain, namely pain catastrophizing and illness-related post-traumatic stress disorder. If underlying depression and anxiety and associated maladaptive coping responses are not treated, patients can experience an increased perception of pain, worsened disability, decreased quality of life, withdrawal from social activities, and increased morbidity and mortality. Meanwhile, interest in nonpharmacologic treatments for pain that targets coping as well as comorbid anxiety and depression has been increasing, particularly given the significant societal damage that has resulted from the opioid epidemic. Evidence-based, nonpharmacologic treatments have shown promise in treating pain in areas outside of nephrology. Currently, little is known about the effects of these treatments among adults with CKD, and particularly end-stage kidney disease, when chronic pain can become debilitating. In this review, we examine patient-centered concepts related to pain that have received little attention in the nephrology literature. We also describe emerging areas of research, including omics technologies for biomarker discovery and advanced symptom clustering methods for symptom phenotyping, which may be useful to future kidney disease research and treatment. [ABSTRACT FROM AUTHOR]

Objective: Self-reported behavior change is used to evaluate the effectiveness of educational outreach interventions delivered to clinicians, such as academic detailing (AD). However, self-reported changes in behavior are often not corroborated with data on actual behavior change. To assess alignment between self-reported practice change intentions and actual opioid prescribing behavior among primary care clinicians after an AD intervention.Methods: We used a difference-in-differences approach to compare pre-post changes in opioid prescribing using data from the Illinois Prescription Monitoring Program. An opioid-focused AD intervention was delivered to primary care clinicians from a large health system in the Chicago metropolitan area from June 2018 to August 2018. Immediately after the AD intervention, clinicians were administered a single-item self-reported practice change measure. Clinicians were categorized into 2 groups on the basis of their responses: (1) intention to change and (2) no-to-moderate intention to change. Outcomes were mean total opioid prescriptions and high-dose opioid prescriptions (≥ 90 morphine milligram equivalents) per clinician per month. Repeated measures linear regression models were used to compare changes in opioid prescribing outcomes between the 2 groups in the 6 months before and after the AD intervention.Results: A total of 149 clinicians were included for analysis. An intention to change was reported by 72 clinicians and no-to-moderate intention to change was reported by 77 clinicians. In the 6 months after the AD intervention, there were 1.48 (95% CI -2.48 to -0.47) fewer total opioid prescriptions and 0.50 (-0.69 to -0.31) fewer high-dose opioid prescriptions per clinician per month in the intention to change group than in the no-to-moderate intention to change group.Conclusion: This study showed considerable alignment between self-reported practice change intentions and actual changes in opioid prescribing behavior. Future opioid-focused educational outreach interventions should consider using standardized single-item practice change measures as an immediate indicator of future behavior change. [ABSTRACT FROM AUTHOR]

Background: Less than half of patients with cardiometabolic disease consistently take prescribed medications. While health insurers and some delivery organizations use claims to measure adherence, most clinicians do not have access during routine interactions. Self-reported scales exist, but their practical utility is often limited by length or cost. By contrast, the accuracy of a new 3-item self-reported measure has been demonstrated in individuals with HIV. We evaluated its concordance with claims-based adherence measures in cardiometabolic disease.Methods: We used data from a recently-completed pragmatic trial of patients with cardiometabolic conditions. After 12 months of follow-up, intervention subjects were mailed a survey with the 3-item measure that queries about medication use in the prior 30 days. Responses were linearly transformed and averaged. Adherence was also measured in claims in month 12 and months 1-12 of the trial using proportion of days covered (PDC) metrics. We compared validation metrics for non-adherence for self-report (average <0.80) compared with claims (PDC <0.80).Results: Of 459 patients returning the survey (response rate: 43.5%), 50.1% were non-adherent in claims in month 12 while 20.9% were non-adherent based on the survey. Specificity of the 3-item metric for non-adherence was high (month 12: 0.83). Sensitivity was relatively poor (month 12: 0.25). Month 12 positive and negative predictive values were 0.59 and 0.52, respectively.Conclusions: A 3-item self-reported measure has high specificity but poor sensitivity for non-adherence versus claims in cardiometabolic disease. Despite this, the tool could help target those needing adherence support, particularly in the absence of claims data. [ABSTRACT FROM AUTHOR]

A limited number of peripheral targets generate pain. Inflammatory mediators can sensitize these. The review addresses targets acting exclusively or predominantly on sensory neurons, mediators involved in inflammation targeting sensory neurons, and mediators involved in a more general inflammatory process, of which an analgesic effect secondary to an anti-inflammatory effect can be expected. Different approaches to address these systems are discussed, including scavenging proinflammatory mediators, applying anti-inflammatory mediators, and inhibiting proinflammatory or facilitating anti-inflammatory receptors. New approaches are contrasted to established ones; the current stage of progress is mentioned, in particular considering whether there is data from a molecular and cellular level, from animals, or from human trials, including an early stage after a market release. An overview of publication activity is presented, considering a IuPhar/BPS-curated list of targets with restriction to pain-related publications, which was also used to identify topics. [ABSTRACT FROM AUTHOR]

Patients with systemic lupus erythematosus (SLE) have a similar risk of myocardial infarction as those with diabetes mellitus (DM). Whether the risk of heart failure (HF) in SLE is similar to the elevated risk in DM is unknown. We sought to estimate the rates and risks for HF hospitalization among US Medicaid patients with SLE and to compare them to those for DM and the general Medicaid population. Using U.S. Medicaid data from 2007–2010, we identified patients with SLE or DM, and a matched cohort from the general Medicaid population and calculated incidence rates (IR), incidence rate ratios (IRR) and adjusted hazard ratios (HR) of a first HF hospitalization. We identified 37,902 SLE (93% female, mean age 40.1 ± 12.1), 76,657 DM (93% female, mean age 40.0 ± 12.1), and 158,695 general Medicaid patients (93% female, mean age 40.2 ± 12.1). The IR per 1000-person years was 6.9 (95% CI 6.3–7.5) for SLE, 6.6 (95% CI 6.2–7.0) for DM, and 1.6 (95% CI 1.5–1.8) for general Medicaid patients. The highest IRR compared to general Medicaid was seen among SLE patients in age group 18–39 (14.7, 95% CI 13.9–15.5). Multivariable-adjusted HRs for HF compared to general Medicaid population were similar for SLE (2.7, 95% CI 2.3–3.1) and DM (3.0, 95% CI 2.6–3.4). The incidence of HF among SLE patients was 2.7-fold higher than general Medicaid patients, and similar to DM. Further investigation into the biologic mechanism of HF among SLE compared to non-SLE and DM patients may shed light on the findings of this study. [ABSTRACT FROM AUTHOR]

Abstract Objective Systemic lupus erythematosus (SLE), which is associated with increased stroke risk, is more prevalent and often more severe among Blacks, Asians, and Hispanics than Whites. We examined racial/ethnic variation in stroke rates and risks, overall and by hemorrhagic versus ischemic subtype, among SLE patients. Methods Within Medicaid (2000–2010), we identified patients aged 18–65 with SLE (≥ 3 ICD-9 710.0 codes, ≥ 30days apart) and ≥12 months of continuous enrollment. Subjects were followed from index date to first stroke event, death, disenrollment, or end of follow-up. Race/ethnicity-specific annual event rates were calculated for stroke overall and by subtypes (hemorrhagic vs. ischemic). We used Cox proportional hazard models to estimate hazard ratios (HR) of stroke by race/ethnicity, adjusting for comorbidities and the competing risk of death. Results Of 65,788 SLE patients, 93.1% were female. Racial/ethnic breakdown was 42% Black, 38% White, 16% Hispanic, 3% Asian, and 1% American Indian/Alaska Natives. Mean follow-up was 3.7 ± 3.0years. After multivariable adjustment, Blacks were at increased risk of overall stroke (HR 1.34 [95%CI 1.18–1.53), hemorrhagic stroke (HR 1.42 [1.00–2.01]), and ischemic stroke (HR 1.33 [1.15–1.52]) compared to Whites. Hispanics were at increased risk of overall stroke (HR 1.25 [1.06–1.47)] and hemorrhagic stroke (HR 1.79 [95% CI 1.22–2.61]), but not ischemic stroke, compared to Whites. Conclusion Among SLE patients enrolled in Medicaid, we observed elevated stroke risk (overall and by subtype) among Blacks and Hispanics compared to Whites, suggesting the importance of early recognition and screening for stroke risk factors among Blacks and Hispanics. [ABSTRACT FROM AUTHOR]

Background Compliance with retainer wear is one of the most challenging aspects of orthodontic treatment and is a concern to all orthodontists. Objectives To determine whether there is a statistically significant difference in compliance in retainer wear during the first year posttreatment. Methods A total of 320 patients were randomly selected from the electronic health records of the University of Pittsburgh, Department of Orthodontics and Dentofacial Orthopedics (Pittsburgh, Pennsylvania). The records were hand-searched for completeness, with age, sex, retainer type, and insurance as the categories. Incomplete records were immediately excluded. A descriptive analysis of the frequency and percentage distribution of variables was made. Categorical data were tested with Fisher exact tests and continuous data with analysis of variance. Results Patient compliance between the 15- to 18-year-old age group and the group older than 24 years, treatment duration over 30 months, Hawley retainers, and state insurance all proved significant ( P < 0.05). Conclusions Compliance with retainer wear declines substantially from the initial visit to the final visit. The most compliant patients over this time period wore the Hawley retainer. Patients with state insurance are the least compliant at both time points. [ABSTRACT FROM AUTHOR]

Primary headaches may be accompanied by increased intracranial blood flow induced by the release of the potent vasodilator calcitonin gene-related peptide (CGRP) from activated meningeal afferents. We aimed to record meningeal and medullary blood flow simultaneously and to localize the sites of CGRP release in rodent preparations in vivo and ex vivo . Blood flow in the exposed rat parietal dura mater and the medulla oblongata was recorded by laser Doppler flowmetry, while the dura was stimulated by topical application of 60 mM potassium chloride (KCl). Samples of jugular venous plasma and cerebrospinal fluid (CSF) collected from the cisterna magna were analysed for CGRP concentrations using an enzyme immunoassay. In a hemisected rat skull preparation lined with dura mater the CGRP releasing effect of KCl superfusion was examined. Superfusion of the dura mater with KCl decreased meningeal blood flow unless alpha-adrenoceptors were blocked by phentolamine, whereas the medullary blood flow was increased. The same treatment caused increased CGRP concentrations in jugular plasma and CSF and induced significant CGRP release in the hemisected rat skull preparation. Anaesthesia of the trigeminal ganglion by injection of lidocaine reduced increases in medullary blood flow and CGRP concentration in the CSF upon meningeal KCl application. CGRP release evoked by depolarisation of meningeal afferents is accompanied by increased blood flow in the medulla oblongata but not the dura mater. This discrepancy can be explained by the smooth muscle depolarising effect of KCl and the activation of sympathetic vasoconstrictor mechanisms. The medullary blood flow response is most likely mediated by CGRP released from activated central terminals of trigeminal afferents. Increased blood supply of the medulla oblongata and CGRP release into the CSF may also occur in headaches accompanying vigorous activation of meningeal afferents. [ABSTRACT FROM AUTHOR]

TRPV4 ion channels have a broad expression profile and were shown to contribute to enhanced pain sensation in inflammation. Directly blocking TRPV4 might run the risk of interfering with normal physiology, and has prompted to explore the interaction with the scaffolding protein AKAP79, an approach successfully used for TRPV1 channels. HEK293t cells express AKAP79, additional transfection did not sensitize human TRPV4. Application of trypsin facilitated responses to TRPV4 agonist GSK1016790A. Using a specific protease-activated receptor 2 agonist, involvement of an A-kinase anchoring protein in TRPV4 activation was demonstrated by inhibition with AKAP inhibitor peptide Ht31. TRPV4 has substantial sequence similarity to TRPV1 in the range interacting with AKAP79. A synthetic peptide, resembling these amino acids and extended by a positive region for transmembrane uptake, was tested. Sensitization of TRPV4 responses could be reduced after exposure to this 771–781::TAT peptide but not by a scrambled control peptide. This validates the concept of targeting the interaction between TRPV4 and AKAP79 and controlling increased TRPV4 activity. [ABSTRACT FROM AUTHOR]

Acidosis occurs in a variety of pathophysiological and painful conditions where it is thought to excite or contribute to excitation of nociceptive neurons. Despite potential clinical relevance the principal receptor for sensing acidosis is unclear, but several receptors have been proposed. We investigated the contribution of the acid-sensing ion channels, transient receptor potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin type 1 (TRPA1) to peripheral pain signaling. We first established a human pain model using intraepidermal injection of the TRPA1 agonist carvacrol. This resulted in concentration-dependent pain sensations, which were reduced by experimental TRPA1 antagonist A-967079. Capsaicin-induced pain was reduced by the TRPV1 inhibitor BCTC. Amiloride was used to block acid-sensing ion channels. Testing these antagonists in a double-blind and randomized experiment, we probed the contribution of the respective channels to experimental acidosis-induced pain in 15 healthy human subjects. A continuous intraepidermal injection of pH 4.3 was used to counter the buffering capacity of tissue and generate a prolonged painful stimulation. In this model, addition of A-967079, BCTC or amiloride did not reduce the reported pain. In conclusion, target-validated antagonists, applied locally in human skin, have excluded the main hypothesized targets and the mechanism of the human acidosis-induced pain remains unclear.Perspective: An acidic milieu is a trigger of pain in many clinical conditions. The aim of this study was to identify the contribution of the currently hypothesized sensors of acid-induced pain in humans. Surprisingly, inhibition of these receptors did not alter acidosis-induced pain. [ABSTRACT FROM AUTHOR]

Introduction Using a quasi-experimental design, we implemented the Patient-Centered Medical Home for Kidney Disease (PCMH-KD), a comprehensive, multidisciplinary care team to improve quality of life and healthcare coordination for adult chronic hemodialysis (CHD) patients. This paper highlights our experience in the first two years of the study. We focus on the process dimensions of Reach , Adoption , and Implementation within the context of the RE-AIM framework. Materials and methods We established a new PCMH-KD model at two outpatient dialysis centers. During the intervention phase, adult patients were recruited for participation and data collection. We monitored RE-AIM measures to identify areas for potential adaptation of the care model. Results During the start-up phase, we engaged patients and stakeholders in planning the intervention, established the new PCMH-KD team, and trained new and continuing clinicians and staff at two dialysis centers. In the intervention phase we recruited 155 patients to participate. Patients had individual visits with the PCP (40%) and the CHWs (92%) ( Reach ). Patient feedback informed procedures for appointment scheduling ( Adoption ). The new PCMH-KD team members were consistent in their roles. With staff changes, some responsibilities were adapted for cross coverage ( Implementation ). Implications After one year of start-up and one year of intervention, active monitoring of Reach, Implementation and Adoption measures have facilitated necessary adaptions in the planned intervention to accommodate scheduling demands and patient feedback in the PCMH-KD model. Insights from this trial may inform care of CHD patients more broadly. [ABSTRACT FROM AUTHOR]

• First self-similar solution for subcritical discharges from vessels for ideal gases. • One dimensionless number sufficient to characterise isentropic, adiabatic discharge. • Practical correlation sufficient to determine discharge duration. • Validation against a parameter study of CFD simulations. Based on the Bernoulli's equation Fischer and Boettcher (2021) developed a model to predict the transient gas discharge from a vessel. Their dimensionless number was able to capture a variation of the molar mass, temperature, vessel volume and opening diameter and showed constant values for these. The influence of the gas, though, could not be completely captured. In this work we improve the model by optimizing the pressure loss coefficient, modifying the dimensionless number and solving the differential equation for determining the pressure over time using the 4th-order Runge-Kutta method. The model was extended to include the influence of the ambient pressure. These improvements lead to the first similarity correlation valid for arbitrary gases. Multiple numerical simulations are performed with ANSYS CFX to verify the similarity model. A grid independence study showed differences below 1 %. The mean deviation between the numerical simulation and the similarity-model is 1.939 %. [ABSTRACT FROM AUTHOR]

Background: Approximately half of patients with chronic cardiometabolic conditions are nonadherent with their prescribed medications. Interventions to improve adherence have been only modestly effective because they often address single barriers to adherence, intervene at single points in time, or are imprecisely targeted to patients who may not need adherence assistance.Objective: To evaluate the effect of a multicomponent, behaviorally tailored pharmacist-based intervention to improve adherence to medications for diabetes, hypertension, and hyperlipidemia.Trial Design: The STIC2IT trial is a cluster-randomized pragmatic trial testing the impact of a pharmacist-led multicomponent intervention that uses behavioral interviewing, text messaging, mailed progress reports, and video visits. Targeted patients are those who are nonadherent to glucose-lowering, antihypertensive, or statin medications and who also have evidence of poor disease control. The intervention is tailored to patients' individual health barriers and their level of health activation. We cluster-randomized 14 practice sites of a large multispecialty group practice to receive either the pharmacist-based intervention or usual care. STIC2IT has enrolled 4,076 patients who will be followed up for 12months after randomization. The trial's primary outcome is medication adherence, assessed using pharmacy claims data. Secondary outcomes are disease control and health care resource utilization.Conclusion: This trial will determine whether a technologically enabled, behaviorally targeted pharmacist-based intervention results in improved adherence and disease control. If effective, this strategy could be a scalable method of offering tailored adherence support to those with the greatest clinical need. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: This study aimed to analyze interreader agreement and diagnostic accuracy of Liver Imaging Reporting and Data System (LI-RADS) in comparison to a nonstandardized 5-point scale and to assess reader acceptance of LI-RADS for clinical routine.Materials and Methods: Eighty-four consecutive patients at risk for hepatocellular carcinoma who underwent liver magnetic resonance imaging were included in this Health Insurance Portability and Accountability Act-compliant retrospective study. Four readers rated the likelihood of hepatocellular carcinoma for 104 liver observations using LI-RADS criteria and a 5-point Likert scale (LIKERT) based on subjective impression in two separate reading sessions. Interreader agreement was assessed using kappa statistics (κ). Diagnostic accuracy was assessed with receiver operating characteristic analysis. Reader acceptance was evaluated with a questionnaire. A sub-analysis of LI-RADS's major features (arterial phase hyper-enhancement, washout, capsule appearance, and threshold growth) and scores for lesions 1.5 cm was performed.Results: LI-RADS showed similar overall interreader agreement compared to LIKERT (κ, 0.44 [95%CI: 0.37, 0.52] and 0.35 [95%CI: 0.27, 0.43]) with a tendency toward higher interreader agreement for LI-RADS. Interreader agreement (κ) was 0.51 (95%CI: 0.38, 0.65) for arterial phase hyper-enhancement, 0.52 (95%CI: 0.39, 0.65) for washout, 0.37 (95%CI: 0.23, 0.52) for capsule appearance, and 0.50 (95%CI: 0.38, 0.61) for threshold growth. Overall interreader agreement for LI-RADS categories was similar between observations <1.5 cm and observations >1.5 cm. Overall diagnostic accuracy for LIKERT and LI-RADS was comparable (area under the receiver operating characteristic curve, 0.86 and 0.87). Readers fully agreed with the statement "A short version of LI-RADS would facilitate the use in clinical routine" (median, 5.0; interquartile range, 2.25).Conclusions: LI-RADS showed similar interreader agreement and diagnostic accuracy compared to nonstandardized reporting. However, further reduction of complexity and refinement of imaging features may be needed. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the use of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI)-derived fat- and liver function-measurements for prediction of future liver remnant (FLR) growth after portal vein occlusion (PVO) in patients scheduled for major liver resection.Methods: Forty-five patients (age, 59 ± 13.9 y) who underwent Gd-EOB-DTPA-enhanced liver MRI within 24 ± 18 days prior to PVO were included in this study. Fat-Signal-Fraction (FSF), relative liver enhancement (RLE) and corrected liver-to-spleen ratio (corrLSR) of the FLR were calculated from in- and out-of-phase (n=42) as well as from unenhanced T1-weighted, and hepatocyte-phase images (n=35), respectively. Kinetic growth rate (KGR, volume increase/week) of the FLR after PVO was the primary endpoint. Receiver operating characteristics analysis was used to determine cutoff values for prediction of impaired FLR-growth.Results: FSF (%) showed significant inverse correlation with KGR (r=-0.41, p=0.008), whereas no significant correlation was found with RLE and corrLSR. FSF was significantly higher in patients with impaired FLR-growth than in those with normal growth (%FSF, 8.1 ± 9.3 vs. 3.0 ± 5.9, p=0.02). ROC-analysis revealed a cutoff-FSF of 4.9% for identification of patients with impaired FLR-growth with a specificity of 82% and sensitivity of 47% (AUC 0.71 [95%CI:0.54-0.87]). Patients with impaired FLR-growth according to the FSF-cutoff showed a tendency towards higher postoperative complication rates (posthepatectomy liver failure in 50% vs. 19%).Conclusions: Liver fat-content, but not liver function derived from Gd-EOB-DTPA-enhanced MRI is a predictor of FLR-growth after PVO. Thus, liver MRI could help in identifying patients at risk for insufficient FLR-growth, who may need re-evaluation of the therapeutic strategy. [ABSTRACT FROM AUTHOR]

Microporous metal formates with the α-Mg(fa) 2 structure (fa = formate, − OOCH) have attracted considerable interest as materials for the storage and separation of small guest molecules. In this study, dispersion-corrected density-functional theory (DFT-D) calculations are employed to calculate the interaction energies for five guest molecules (acetylene, carbon dioxide, methane, nitrogen, hydrogen) adsorbed in the pores of metal formates with different metal centres (Mg, Mn, Fe, Co, Zn). For each guest-adsorbent combination, the average interaction strength is calculated as Boltzmann-weighted average of the DFT-D interaction energies obtained for individual adsorption sites. For systems for which experimentally measured heats of adsorption have been reported, the averaged energies agree very well with experimental values. Therefore, the DFT-D results can be used to predict the potential of metal formates as adsorbents for different applications. While metal formates may be of limited use for many gas storage applications due to their small free volume, the high affinity of Co(fa) 2 and Zn(fa) 2 towards methane and acetylene could render them interesting for storage applications in which the affinity is more important than the uptake capacity. With regard to gas separation and purification, Co(fa) 2 emerges as the most attractive system for the selective adsorption of acetylene and carbon dioxide over other species, while Zn(fa) 2 and Mg(fa) 2 are more promising for the separation of methane from nitrogen or hydrogen. Correlations between the averaged interaction energies and simple descriptors of pore size and pore volume are analysed. [ABSTRACT FROM AUTHOR]

Bioclimatic conditions are thought to have an impact on the frequency of dental abscesses but previous studies have suffered from small patient cohorts, methodological obstacles, and restriction to a single site resulting in limited geographic and meteorological variability. The aim of the present study was to investigate the influence of environmental temperature and barometric pressure on the frequency of dental abscesses. Three maxillofacial and two dental clinics in Vienna retrospectively provided a total of 19,218 patients with dentoalveolar abscesses who were treated by intraoral incision between 1998 and 2011. Daily records from six local meteorological stations were consulted to assess daily meteorological parameters. Univariate and multivariate hurdle count regression models were fitted to estimate the effect of daily average barometric pressure and temperature on registered abscess frequencies. Temporal confounders causing variance of the observed abscess frequencies – such as weekday, business day, and month – were taken into consideration. On days of low barometric pressure a significant rise in dental abscess frequency was observed, even when adjusting for confounders. Environmental temperature, in contrast, did not show any effect. In conclusion, bioclimatic conditions affect health as low barometric pressure increases the number of patients with dental abscesses. [ABSTRACT FROM AUTHOR]

Background It was the purpose of this paper to analyze structural, functional, and electrophysiologic variables that may determine preserved overhead function for patients with massive rotator cuff tears. Methods Nineteen patients (20 shoulders) were prospectively included in either the pseudoparalytic (n = 9) or the non-pseudoparalytic group (n = 11). Fatty infiltration was graded according to Goutallier, and anterior (subscapularis) and posterior (infraspinatus and teres minor) tear extension was graded 0 (no involvement) to 4 (full tear) on magnetic resonance imaging. Glenohumeral and scapulothoracic rhythm was assessed by fluoroscopic motion analysis, and electromyographic evaluation of the deltoid muscle was performed. Results We found no significant difference of fatty infiltration of the supraspinatus (3.9 vs 3.6), infraspinatus (3.9 vs 3.8), and teres minor (1.7 vs 0.6) or of the posterior tear extension (2.6 vs 2.0) between pseudoparalytic and non-pseudoparalytic shoulders. Global tear extension in the parasagittal plane (205° vs 163°) and subscapularis involvement (2.6 vs 1.2), however, showed significant differences between the two groups, and no patient with a full-thickness supraspinatus and infraspinatus tear with extension into the inferior half of the subscapularis was able to lift the arm to 90°. Fluoroscopic assessment revealed almost total loss of active glenohumeral abduction in the pseudoparalytic group. Conclusion Despite global tear extension, the single most important predictor for preserved shoulder function is the integrity of the inferior subscapularis insertion. Furthermore, electromyographic evaluation identifies a well-differentiated deltoid innervation as beneficial for a well-preserved shoulder function, but it does not protect from pseudoparalysis. [ABSTRACT FROM AUTHOR]

Cellular responsiveness to external stimuli can be altered by extracellular mediators which activate membrane receptors, in turn signalling to the intracellular space via calcium, cyclic nucleotides, membrane lipids or enzyme activity. These signalling events trigger a cascade leading to an effector which can be a channel, an enzyme or a transcription factor. The effectiveness of these intracellular events is enhanced when they are maintained in close proximity by anchoring proteins, which assemble complexes of signalling molecules such as kinases together with their targets, and in this way enhance both the speed and the precision of intracellular signalling. The A kinase anchoring protein (AKAP) family are adaptor proteins originally named for their ability to associate Protein Kinase A and its targets, but several other enzymes bound by AKAPs have now been found and a wide variety of target structures has been described. This review provides an overview of anchoring proteins involved in pain signalling. The key anchoring proteins and their ion channel targets in primary sensory neurons responding to painful stimuli (nociceptors) are discussed. [ABSTRACT FROM AUTHOR]

Objective: Mastication may be able to activate endogenous pain inhibitory mechanisms and therefore lead to modulation of nociceptive processing. The purpose of this study was to examine the possible effect of food consistency on noxious input from the spinal system. Methods: Three groups of adult male Sprague-Dawley rats were given an injection of complete Freund adjuvant in a hind paw 10 days after eating soft or hard food (one group received a saline injection--the control group [C]; the other group (D) received no injection). Nocifensive behavior was assessed with the use of the hot plate and tail flick assays at 1, 3, 6, and 12 hours and at 6.5 days after injection for groups A/B, and c-Fos activity was assessed in the brain after testing. Groups C/D had hot plate testing at 1 hour and 6.5 days. The data were analyzed by general linear modeling and 1-way analysis of variance. Results: There was a small increase in the hot plate percent maximum possible effect (MPE) from -45.7 to -61.1 in group A over the length of the experiment, but a very small decrease for group B over the same period (-33.5 to -28.8). For the saline control group, there was a small increase toward 0 %MPE over the same time frame (-15.0 to 1.7). The %MPE differences were significant between groups A and C (P < .0005), but not significant between the other groups (F = 13.34, df = 2, P = .001, observed power = 99%). Using the pooled results (all time points), the differences between all groups were significant (P < .0005). There were no significant differences in the tail flick test. c-Fos was mainly observed in the raphe pallidus area with significant differences between groups A and B at 3 and 6 hours after injection of CFA (P = .027 and .022, respectively). Conclusions: The results of this study indicate that food consistency (hardness) influences nocifensive behavior in this animal model via a descending pathway operating at the supraspinal level. [ABSTRACT FROM AUTHOR]

Highlights: [•] 5(10)-Estrene-3β,17α-diol is an essential reference material for doping analysis in horse-racing laboratories. [•] A stereoselective synthesis of this compound is described. [•] The 3β alcohol was obtained via asymmetric transfer hydrogenation using Noyori catalyst. [•] Final purification was performed according to a chemoenzymatic process. [Copyright &y& Elsevier]

• Analytical model for subcritical discharge from a vessel for ideal gases. • Validation against CFD Simulations. • Correlation for discharge duration without any further fluid mechanical knowledge. • Two dimensionless numbers sufficient to cover discharge duration. Based on the Bernoulli's equation a fast and accurate model is developed to predict the transient gas discharge from a pressure vessel. The system is considered adiabatic, isentropic, compressible, and subcritical and the gas is considered ideal. Based on an energy balance, a simplified method is presented to check whether the system can be assumed to be adiabatic. The opening of the vessel should be at least five outlet diameters D 2 away from the other walls or corners in order to fulfil the assumption that the flow velocity inside the vessel is negligible. The model is compared with CFD simulations, which are performed with ANSYS CFX©. Furthermore, a new dimensionless number is introduced, which takes into account the gas and vessel properties. In combination with the developed discharge model and a conducted parameter study, a universal correlation for estimating the discharge duration is developed. The application does not require any further knowledge of fluid mechanics, making it a quick estimation tool for everyone. The model is able to calculate isentropic cooling and the resulting transient behaviour with a deviation from the simulation of <12%. The model and the correlation for the dimensionless number are able to capture the discharge behaviour of any gases and vessels that meet the requirements listed above. The correlation is a fast and accurate tool for estimating safety problems in process engineering. [ABSTRACT FROM AUTHOR]

Objective: The incidence of hospital-acquired Clostridium difficile infection (CDI) has increased rapidly over the past decade; patients undergoing major surgery, including coronary artery bypass grafting (CABG), are at particular risk. Intravenous vancomycin exposure has been identified as an independent risk factor for CDI, but this is controversial. It is not known whether vancomycin administered for surgical site infection prophylaxis increases the risk of CDI. Methods: Using data from the Premier Perspective Comparative Database, we assembled a cohort of 69,807 patients undergoing CABG surgery between 2004 and 2010 who received either a cephalosporin alone (65.1%) or a cephalosporin plus vancomycin (34.9%) on the day of surgery. Patients were observed for CDI until discharge from the index hospitalization. In these groups, we evaluated the comparative rate of postoperative CDI with Cox models; confounding was addressed using propensity scores. Results: In all, 77 (0.32%) of the 24,393 patients receiving a cephalosporin plus vancomycin and 179 (0.39%) of the 45,414 patients receiving a cephalosporin alone had postoperative CDI (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.56-0.95). After adjusting for confounding variables with either propensity score matching or stratification, there was no meaningful association between adjuvant vancomycin exposure and postoperative CDI (HR, 0.85; 95% CI, 0.61-1.19; and HR, 0.85; 95% CI, 0.63-1.15, respectively). Results of multiple sensitivity analyses were similar to the main findings. Conclusions: After adjustment for patient and surgical characteristics, a short course of prophylactic vancomycin was not associated with an increased risk of CDI among patients undergoing CABG surgery. [Copyright &y& Elsevier]

Abstract: This work describes the design and implementation of an auction system using secure multiparty computation techniques. Our aim is to produce a system that is practical under actual field constraints on computation, memory, and communication. The underlying protocol is privacy-preserving, that is, the winning bid is determined without information about the losing bids leaking to either the auctioneer or other bidders. Practical implementation of the protocol is feasible using circuit-based cryptographic proofs along with additively homomorphic bit commitment. Moreover, we propose the development of a Proof Certificate standard. These certificates convey sufficient information to recreate the cryptographic proofs and verify them offline. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate the accuracy and confidence in diagnosing liver metastases using combined gadolinium-EOB-DTPA (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI)/diffusion-weighted imaging (DWI) in comparison to Gd-EOB-DTPA enhanced MRI and DWI alone. Materials and methods: Forty-three patients (age, 58±13 years) with 89 liver lesions (28 benign, 61 malignant) underwent liver MRI for suspected liver metastases. Three image sets (DWI, Gd-EOB-DTPA and combined Gd-EOB-DTPA/DWI) in combination with unenhanced T1- and T2-weighted images were reviewed by three readers. Detection rates of focal liver lesions were assessed and diagnostic accuracy was evaluated by calculating the areas under the receiver-operating-characteristics curve (AUC). Confidence in diagnosis was evaluated on a 3-point scale. Histopathology and imaging follow-up served as the standard of reference. Results: Detection of liver lesions and confidence in final diagnosis for all readers were significantly higher for the combined Gd-EOB-DTPA/DWI dataset than for DWI. The combination of DWI and Gd-EOB-DTPA rendered a significantly higher confidence in final diagnosis (2.44 vs. 2.50) than Gd-EOB-DTPA alone for one reader. For two readers, accuracy in diagnosis of liver metastases was significantly higher for Gd-EOB-DTPA/DWI (AUCs of 0.84 and 0.83) than for DWI datasets (AUCs of 0.73 and 0.72). Adding DWI to Gd-EOB-DTPA did not significantly increase diagnostic accuracy as compared to Gd-EOB-DTPA imaging alone. Conclusion: Addition of DWI sequences to Gd-EOB-DTPA enhanced MRI did not significantly increase diagnostic accuracy as compared to Gd-EOB-DTPA enhanced MRI alone in the diagnosis of liver metastases. However, the increase in diagnostic confidence might justify acquisition of DWI sequences in a dedicated MRI protocol. [Copyright &y& Elsevier]

Abstract: The anti-diabetic drug glibenclamide inhibits K(ATP) channels in pancreatic β-cells and stimulates insulin release. It also causes adverse effects, among which are abdominal pain, gastrointestinal disturbances and nocturia. We report that glibenclamide activates human TRPA1 in a concentration range that is commonly used to induce inhibition of K(ATP) channels in vitro. Glibenclamide generates calcium transients in HEK293t cells transiently transfected with human TRPA1, which are inhibited by the selective TRPA1 antagonist HC030031 and also evokes outwardly rectifying currents mediated by recombinant TRPA1. Glibenclamide activates a subpopulation of mouse primary sensory neurons, most of which are also sensitive to the selective TRPA1 agonist mustard oil. This glibenclamide sensitivity is completely abolished by genetic ablation of TRPA1. Taken together, our data demonstrate that glibenclamide is an agonist of human TRPA1, which may explain some of the adverse effects of the drug. [Copyright &y& Elsevier]

Illicit drug use has been associated with chronic kidney disease (CKD) in select populations, but it is unknown whether the same association exists in the general population. By using data from the National Health and Nutrition Examination Survey 2005–2008, we conducted a cross-sectional analysis of 5861 adults who were questioned about illicit drug use, including cocaine, methamphetamines, and heroin, during their lifetime. The primary outcome was CKD as defined by an estimated glomerular filtration rate ≤60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration equation or by microalbuminuria. We also examined the association between illicit drug use and blood pressure (BP) ≥120/80, ≥130/85, and ≥140/90 mm Hg. Logistic regression was used to examine the association between illicit drug use and CKD and BP. Mean estimated glomerular filtration rate was similar between illicit drug users and nonusers (100.7 vs 101.4 mL/min/1.73 m2, P = 0.4), as was albuminuria (5.7 vs 6.0 mg/g creatinine, P = 0.5). Accordingly, illicit drug use was not significantly associated with CKD in logistic regression models (odds ratio [OR], 0.98; confidence interval [CI], 0.75–1.27) after adjusting for other important factors. However, illicit drug users had higher systolic (120 vs 118 mm Hg, P = 0.04) and diastolic BP (73 vs 71 mm Hg, P = 0.0003) compared with nonusers. Cocaine use was independently associated with BP ≥130/85 mm Hg (OR, 1.24; CI, 1.00–1.54), especially when used more during a lifetime (6–49 times; OR, 1.42; CI, 1.06–1.91). In a representative sample of the US population, illicit drug use was not associated with CKD, but cocaine users were more likely to have elevated BP. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the impact of reductions in statin and clopidogrel copayments on cardiovascular resource utilization, major coronary events, and insurer spending. Background: Copayments are widely used to contain health spending but cause patients to reduce their use of essential cardiovascular medications. Reducing copayments for post–myocardial infarction secondary prevention has beneficial effects, but the impact of this strategy for lower risk patients and other drugs remains unclear. Methods: An evaluation was conducted of health care spending and resource use by a large self-insured employer that reduced statin copayments for patients with diabetes or vascular disease and reduced clopidogrel copayments for all patients prescribed this drug. Eligible individuals in the intervention company (n = 3,513) were compared with a control group from other companies without such a policy (n = 49,803). Analyses were performed using segmented regression models with generalized estimating equations. Results: Lowering copayments was associated with significant reductions in rates of physician visits (relative change: statin users 0.80; 95% confidence interval [CI]: 0.57 to 0.98; clopidogrel users: 0.87; 95% CI: 0.59 to 0.96) and hospitalizations and emergency department admissions (relative change: statin users 0.90; 95% CI: 0.80 to 0.92; clopidogrel users: 0.89; 95% CI: 0.74 to 0.90) although not major coronary events. Patient out-of-pocket spending for drugs and other medical services decreased (relative change: statin users 0.79; 95% CI: 0.75 to 0.83; clopidogrel users 0.74; 95% CI: 0.66 to 0.82). Providing more generous coverage did not increase overall spending (relative change: statin users 1.03; 95% CI: 0.97 to 1.09; clopidogrel users 0.94; 95% CI: 0.87 to 1.03). Conclusions: Lowering copayments for statins and clopidogrel was associated with reductions in health care resource use and patient out-of-pocket spending. The policy appeared cost neutral with respect to overall health spending. [Copyright &y& Elsevier]

Rationale and Objectives: The aim of this study was to evaluate the accuracy of dual-echo (DE) magnetic resonance imaging (MRI) with and without fat and water separation for the quantification of liver fat content (LFC) in vitro and in patients undergoing liver surgery, with comparison to histopathologic analysis. Materials and Methods: MRI was performed on a 1.5-T scanner using a three-dimensional DE MRI sequence with automated reconstruction of in-phase (IP) and out-of-phase (OP) and fat-signal-only and water-signal-only images. LFC was estimated by fat fractions from IP and OP images (MRIIP/OP) and from Dixon-based fat-only and water-only images (MRIDIxON). Seven phantoms containing a titrated mixture of liver and fat from 0% to 50% were examined. Forty-three biopsies in 22 patients undergoing liver surgery were prospectively evaluated by a pathologist by traditional determination of the cell-count fraction and by a computer-based algorithm, the latter serving as the reference standard. Results: In vitro, both MRIIP/OP and MRIDIxON were significantly correlated with titrated LFC (r = 0.993, P < .001), with a smaller measurement bias for MRIIP/OP (+2.6%) than for MRIDIxON (+4.5%). In vivo, both MRIIP/OP and MRIDIxON from DE MRI were correlated significantly better with computer-based histologic results (P < .001) and showed significantly smaller measurement bias (4.8% vs 21.1%) compared to histologic cell-count fraction (P < .001). Measurement bias was significantly smaller for MRIIP/OP than for MRIDIxON (P < .001). Conclusions: DE MRI allows the accurate quantification of LFC in a surgical population, outperforming traditional histopathologic analysis. DE MRI without fat and water separation shows the highest accuracy and smallest measurement bias for the quantification of LFC. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To prospectively analyze the correlation between parameters of liver perfusion from technetium99m-macroaggregates of albumin (99mTc-MAA) single photon emission computed tomography (SPECT) with those obtained from dynamic CT perfusion in patients with primary or metastatic liver malignancy. Materials and Methods: Twenty-five consecutive patients (11 women, 14 men; mean age 60.9 ± 10.8; range: 32–78 years) with primary (n = 5) or metastatic (n = 20) liver malignancy planned to undergo selective internal radiotherapy underwent dynamic contrast-enhanced CT liver perfusion imaging (four-dimensional spiral mode, scan range 14.8 cm, 15 scans, cycle time 3 seconds) and 99mTc-MAA SPECT after intraarterial injection of 180 MBq 99mTc–MAA on the same day. Data were evaluated by two blinded and independent readers for the parameters arterial liver perfusion (ALP), portal venous perfusion (PVP), and total liver perfusion (TLP) from CT, and the 99mTc-MAA uptake-ratio of tumors in relation to normal liver parenchyma from SPECT. Results: Interreader agreements for quantitative perfusion parameters were high for dynamic CT (r = 0.90–0.98, each P < .01) and 99mTc -MAA SPECT (r = 0.91, P < .01). Significant correlation was found between 99mTc-MAA uptake ratio and ALP (r = 0.7, P < .01) in liver tumors. No significant correlation was found between 99mTc-MAA uptake ratio, PVP (r = −0.381, P = .081), and TLP (r = 0.039, P = .862). Conclusion: This study indicates that in patients with primary and metastatic liver malignancy, ALP obtained by dynamic CT liver perfusion significantly correlates with the 99mTc-MAA uptake ratio obtained by SPECT. [Copyright &y& Elsevier]