Τρίτη, 19 Δεκεμβρίου 2017

Genetic variants in microRNA genes and targets associated with cardiovascular disease risk factors in the African-American population

Abstract

The purpose of this study is to identify microRNA (miRNA) related polymorphism, including single nucleotide variants (SNVs) in mature miRNA-encoding sequences or in miRNA-target sites, and their association with cardiovascular disease (CVD) risk factors in African-American population. To achieve our objective, we examined 1900 African-Americans from the Atherosclerosis Risk in Communities study using SNVs identified from whole-genome sequencing data. A total of 971 SNVs found in 726 different mature miRNA-encoding sequences and 16,057 SNVs found in the three prime untranslated region (3′UTR) of 3647 protein-coding genes were identified and interrogated their associations with 17 CVD risk factors. Using single-variant-based approach, we found 5 SNVs in miRNA-encoding sequences to be associated with serum Lipoprotein(a) [Lp(a)], high-density lipoprotein (HDL) or triglycerides, and 2 SNVs in miRNA-target sites to be associated with Lp(a) and HDL, all with false discovery rates of 5%. Using a gene-based approach, we identified 3 pairs of associations between gene NSD1 and platelet count, gene HSPA4L and cardiac troponin T, and gene AHSA2 and magnesium. We successfully validated the association between a variant specific to African-American population, NR_039880.1:n.18A>C, in mature hsa-miR-4727-5p encoding sequence and serum HDL level in an independent sample of 2135 African-Americans. Our study provided candidate miRNAs and their targets for further investigation of their potential contribution to ethnic disparities in CVD risk factors.



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Diagnostic exome sequencing in children: A survey of parental understanding, experience and psychological impact

ABSTRACT

Clinical exome sequencing (CES) is increasingly being used as an effective diagnostic tool in the field of pediatric genetics. We sought to evaluate the parental experience, understanding and psychological impact of CES by conducting a survey study of English-speaking parents of children who had diagnostic CES. Parents of 192 unique patients participated. The parent's interpretation of the child's result agreed with the clinician's interpretation in 79% of cases, with more frequent discordance when the clinician's interpretation was uncertain. The majority (79%) reported no regret with the decision to have CES. Most (65%) reported complete satisfaction with the genetic counseling experience, and satisfaction was positively associated with years of genetic counselor (GC) experience. The psychological impact of CES was greatest for parents of children with positive results and for parents with anxiety or depression. The results of this study are important for helping clinicians prepare families for the possible results and variable psychological impact of CES. The frequency of parental misinterpretation of test results indicates the need for additional clarity in the communication of results. Finally, while the majority of patients were satisfied with their genetic counseling, satisfaction was lower for new GCs, suggesting a need for targeted GC training for genomic testing.

Thumbnail image of graphical abstract

The aMICRA score was used to assess impact, including distress, uncertainty and positivity (reversed scored) of the genetic test results on the parents. On average, the aMICRA was 12 points higher (more negative impact) in parents who interpreted the results as positive and seven points higher for those who interpreted the results as uncertain compared to those who interpreted the results as negative (p<0.0001, p=0.02). Overall the majority of parents correctly interpreted their child's exome sequencing results. Parental misinterpretation occurred most frequently when the clinician interpreted the results as uncertain.



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Bilateral deficit of spring-like behaviour during hopping in sprinters

Abstract

Purpose

Unilateral leg stiffness is a key contributor to sprint running speed, thereby great bilateral deficit (BLD) of leg stiffness would be expected to be observed in sprinters. However, it remains clear only BLD of leg stiffness at the preferred hopping frequency in non-sprinters. The purpose of this study was to clarify the BLD of spring-like behaviour in hopping at various frequencies and the effect of chronic adaptation via sprint running experience on BLD during the hopping.

Methods

Fifteen male experienced sprinters and 12 male novices participated in this study. They were instructed to hop in place at three frequencies (2.0, 2.5, and 3.0 Hz), and to perform hopping with maximal effort. Ground reaction forces (GRF) of both legs during the hopping were recorded using two force plates.

Results

At higher hopping frequencies during the unilateral and bilateral hopping, smaller peak value of vertical GRF (F max) and greater leg stiffness (K leg) were significantly observed. The BLD index of F max and the BLD index of K leg were significantly smaller at higher hopping frequencies. No significant differences of BLD index of F max and BLD index of K leg were observed between sprinters and novices.

Conclusion

Our results demonstrate that neuromuscular inhibition in the contralateral leg changes during the hopping based on hopping frequency. This suggests that plyometric training in the beginning of rehabilitation should involve bilateral jumping at a high frequency. In experienced sprinters, detailed mechanics of chronic neuromuscular adaptation via unilateral facilitation of spring-like behaviour should be assessed by measuring electromyographic activity.



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Event-related potentials of attentional bias toward faces in the dot-probe task: A systematic review

Abstract

The dot-probe task is a common task to assess attentional bias toward different stimuli and how groups differ (e.g., attentional bias in anxiety disorders). However, measuring reaction time has been suggested to be unreliable. Neuroimaging methods such as fMRI were shown to be more reliable in assessing attentional bias, but fMRI has poor temporal resolution and therefore cannot assess timing of attention. ERPs have been used to examine the time course of attentional bias. Although ERP research may be more reliable than reaction time, there have been inconsistencies in the literature. This review systematically searched for articles that used the dot-probe task with facial expressions and measured neural correlates with ERP. We found that some of the inconsistencies might be the cause of methodological differences (e.g., timing of stimuli), differences in emotional expression, and/or sample differences (e.g., sex, age, etc.). Suggestions on how future research could address the issues presented in this review were discussed.



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Spatial versus temporal inhibition in dystonia

Dystonia is a motor disorder characterized by involuntary muscle contractions, frequently causing twisted postures. A pathophysiological hallmark of dystonia is reduced motor inhibition at multiple levels of the central nervous system including the spinal cord, brainstem and cortex. In addition, it is widely accepted that the sensory system is involved in dystonia. A well-known and fascinating phenomenon is the sensory trick. Touching a body part, usually at a location close to where dystonia occurs such as the neck or face in cervical dystonia or blepharospasm, alleviates dystonia symptoms.

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The implant effect after intracranial electrode placement: is transient clinical improvement explained by post-implantation electrophysiological changes?

It has been repeatedly observed that implanting electrodes in the brain or on the brain is occasionally associated with a transient improvement in seizure control. This improvement was observed with responsive neurostimulation (Morrell et al., 2011), deep brain stimulation (Velasco et al., 2006; Fisher et al., 2010; Valentin et al., 2013), and even diagnostic intracranial electrode implantation (Schulze-Bonhage et al., 2010; Roth et al., 2012; Kovac et al., 2014). In the pivotal trial of anterior thalamic stimulation, there was a 21-22% median seizure frequency reduction in the first month after implantation, prior to randomization (Fisher et al., 2010).

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Restoration of metabolic health by decreased consumption of branched-chain amino acids

Abstract

Obesity and diabetes are increasing problems around the world, and while even moderate weight loss can improve metabolic health, reduced calorie diets are notoriously difficult to sustain. Branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) are elevated in the blood of obese, insulin-resistant humans and rodents. We recently demonstrated that specifically reducing dietary levels of BCAAs has beneficial effects on the metabolic health of young, growing mice, improving glucose tolerance and modestly slowing fat mass gain. Here, we examine the hypothesis that reducing dietary BCAAs will promote weight loss, reduce adiposity, and improve blood glucose control in diet-induced obese mice with pre-existing metabolic syndrome. We find that specifically reducing dietary BCAAs rapidly reverses diet-induced obesity and improves glucoregulatory control in diet-induced obese mice. Most dramatically, mice eating an otherwise unhealthy high-calorie, high-sugar Western diet with reduced levels of BCAAs lost weight and fat mass rapidly until regaining a normal weight. Importantly, this normalization of weight was mediated not by caloric restriction or increased activity, but by increased energy expenditure, and was accompanied by a transient induction of the energy balance regulating hormone FGF21. Consumption of a Western diet reduced in BCAAs was also accompanied by a dramatic improvement in glucose tolerance and insulin resistance. Our results link dietary BCAAs to the regulation of metabolic health and energy balance in obese animals, and suggest that specifically reducing dietary BCAAs may represent a highly translatable option for the treatment of obesity and insulin resistance.

This article is protected by copyright. All rights reserved



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The implant effect after intracranial electrode placement: is transient clinical improvement explained by post-implantation electrophysiological changes?

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Publication date: Available online 19 December 2017
Source:Clinical Neurophysiology
Author(s): Bassel Abou-Khalil, Antonio Valentin




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Spatial versus temporal inhibition in dystonia

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Publication date: Available online 19 December 2017
Source:Clinical Neurophysiology
Author(s): Robert Chen




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REPlicating RAPid Microfluidics: Self-Replicating Printer for Hydrophobic Pattern Deposition

3D Printing and Additive Manufacturing Dec 2017, Vol. 4, No. 4: 231-238.


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Biocompatibility of Photopolymers in 3D Printing

3D Printing and Additive Manufacturing Dec 2017, Vol. 4, No. 4: 185-191.


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Beyond the Quest from Personal to Production

3D Printing and Additive Manufacturing Dec 2017, Vol. 4, No. 4: 183-183.


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Mechanical Properties of Interfaces in Inkjet 3D Printed Single- and Multi-Material Parts

3D Printing and Additive Manufacturing Dec 2017, Vol. 4, No. 4: 193-199.


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Additive Manufactured Biomimicking Actuator with Shape Memory Polymer Composite for Prosthetic Actuators

3D Printing and Additive Manufacturing Dec 2017, Vol. 4, No. 4: 201-213.


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The Effectiveness of Progressive Aerobic Interval Training in Cardiac Rehabilitation

AbstractIntroductionAerobic interval training (AIT) has recently emerged as a more effective strategy than moderate intensity continuous exercise (MICE) for improving VO2peak in CAD patients. The primary purpose of this retrospective study was to describe the change in VO2peak, and CV risk profile characteristics (secondary outcomes) after progressive AIT practiced in the largest, outpatient cardiac rehabilitation (CR) program in North America compared to usual care CR involving MICE.MethodsElectronic database records were retrieved from consecutively enrolled patients with CAD who attended the Toronto Rehabilitation Institute, between January 1, 2005 to December 31, 2015. Patients were then separated into two, age and sex propensity score matched groups: 772 patients were prescribed 26 weeks of MICE (60-80% of VO2peak, 5 times/week) as per usual care CR (56.0±9.2 years; 12% female/88% male; VO2peak: 20.8±5.9 ml⋅kg-1⋅min-1), and 772 patients were prescribed 26 weeks of progressive walk/jog intervals (15min/mile walking pace, 12min/mile jogging pace, 5 times/week) (55.9±9.3 years; 12% female/88% male; VO2peak: 24.8±5.7 ml⋅kg-1 ⋅min-1). Treatment effect analysis of AIT on VO2peak and CV risk profile characteristics was performed using multiple regression with baseline values as covariates.ResultsTreatment effect analysis revealed a 3.84 ml⋅kg-1⋅min-1 superior improvement in VO2peak in the AIT group compared to usual care MICE group (p

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Preoperative Blood Tests Conducted Before Low-Risk Surgery in Japan: A Retrospective Observational Study Using a Nationwide Insurance Claims Database

BACKGROUND: Routine preoperative testing is discouraged before low-risk surgery because testing does not provide any beneficial effect in terms of patient outcome. However, few studies have assessed the utilization of hospital health care resources in terms of preoperative tests in a real-world setting. Here, we aimed to assess the prevalence and factors associated with preoperative blood tests before low-risk surgery in Japan. METHODS: In this retrospective observational study, we used the nationwide insurance claims data of Japan. Patients who underwent low-risk surgeries between April 1, 2012, and March 31, 2016, were included. Our primary outcome was the receipt of any preoperative tests within 60 days before an index procedure: complete blood count, basic metabolic panel, coagulation tests, and liver function tests. We performed a descriptive analysis to estimate the proportions of preoperative blood tests, and examined the associations between patient-level and institutional-level factors and preoperative blood tests, using multilevel logistic regression analysis. Interinstitutional variation in the utilization of preoperative tests was summarized using the median odds ratio (OR). RESULTS: The study sample included 59,818 patients (mean [standard deviation] age, 44.0 [11.3] years; 33,574 [56.1%] women) from 9746 institutions. The overall proportion of each test was: complete blood count, 58.7%; metabolic panel, 47.8%; coagulation tests, 36.6%; and liver function tests, 48.5%. The proportion receiving any preoperative tests in the overall sample was 59.5%. Multilevel logistic regression analysis indicated that preoperative blood tests were associated with the Charlson comorbidity index score (score ≥3: adjusted OR, 4.21; 95% confidence interval [CI], 3.69–4.80), anticoagulant use (adjusted OR, 4.12; 95% CI, 2.35–7.22), type of anesthesia (general anesthesia: adjusted OR, 5.69; 95% CI, 4.85–6.68; regional anesthesia: adjusted OR, 3.76; 95% CI, 3.28–4.30), surgical setting (inpatient procedure: adjusted OR, 3.64; 95% CI, 3.30–4.00), and number of beds (≥100 beds: adjusted OR, 3.61; 95% CI, 3.19–4.08). The median institutional-specific proportion of preoperative tests was 40.0% (interquartile range, 0%–100%). The median OR for interinstitutional variation in ordering preoperative tests was 4.34. These findings were consistent across a sensitivity analysis. CONCLUSIONS: Preoperative blood tests were performed before 59.5% of low-risk surgeries. Preoperative tests were associated with the type of anesthesia, patient characteristics, and medical facility status. There was a substantial interinstitutional variation in the utilization of preoperative tests. Accepted for publication November 8, 2017. Funding: Support was provided solely from institutional and/or departmental sources. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Koji Kawakami, MD, PhD, Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoecho, Sakyoku, Kyoto 6068501, Japan. Address e-mail to kawakami.koji.4e@kyoto-u.ac.jp. © 2017 International Anesthesia Research Society

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Modifiable and Nonmodifiable Factors Associated With Perioperative Failure of Extraglottic Airway Devices

BACKGROUND: Extraglottic airway device (EGA) failure can be associated with severe complications and adverse patient outcomes. Prior research has identified patient- and procedure-related predictors of EGA failure. In this retrospective study, we assessed the incidence of perioperative EGA failure at our institution and identified modifiable factors associated with this complication that may be the target of preventative or mitigating interventions. METHODS: We performed a 5-year retrospective analysis of adult general anesthesia cases managed with EGAs in a single academic center. Univariable and multivariable logistic regressions were used to identify clinically modifiable and nonmodifiable factors significantly associated with 3 different types of perioperative EGA failure: (1) "EGA placement failure," (2) "EGA failure before procedure start," and (3) "EGA failure after procedure start." RESULTS: A total of 19,693 cases involving an EGA were included in the analysis dataset. EGA failure occurred in 383 (1.9%) of the cases. EGA placement failure occurred in 222 (1.13%) of the cases. EGA failure before procedure start occurred in 76 (0.39%) of the cases. EGA failure after procedure start occurred in 85 (0.43%) of the cases. Factors significantly associated with each type of failure and controllable by the anesthesia team were as follows: (1) EGA placement failure: use of desflurane (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.23–2.25) and EGA size 4 or 5 vs 2 or 3 (OR, 0.07; 95% CI, 0.05–0.10); (2) EGA failure before procedure start: use of desflurane (OR, 2.05; 95% CI, 1.23–3.40) and 3 or more placement attempts (OR, 4.69; 95% CI, 2.57–8.56); and (3) EGA failure after procedure start: 3 or more placement attempts (OR, 2.06; 95% CI, 1.02–4.16) and increasing anesthesia time (OR, 1.35; 95% CI, 1.17–1.55). CONCLUSIONS: The overall incidence of EGA failure was 1.9%, and EGA placement failure was the most common type of failure. We also found that use of desflurane and use of smaller EGA sizes in adult patients were factors under the direct control of anesthesia clinicians associated with EGA failure. An increasing number of attempts at EGA placement was associated with later device failures. Our findings also confirm the association of EGA failure with previously identified patient- and procedure-related factors such as increased body mass index, male sex, and position other than supine. Accepted for publication September 29, 2017. Funding: None. The authors declare no conflicts of interest. This study was entirely conducted at Barnes Jewish Hospital and the School of Medicine of Washington University in St Louis. Reprints will not be available from the authors. Address correspondence to Andrea Vannucci, MD, DEAA, Department of Anesthesiology, University of Mississippi Medical Center-School of Medicine, 2500 N State St, Jackson, MS 39216. Address e-mail to avannucci@umc.edu. © 2017 International Anesthesia Research Society

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Surveying the Literature

No abstract available

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Differential Effects of Anesthetics and Opioid Receptor Activation on Cardioprotection Elicited by Reactive Oxygen Species–Mediated Postconditioning in Sprague-Dawley Rat Hearts

BACKGROUND: Despite an array of cardioprotective interventions identified in preclinical models of ischemia–reperfusion (IR) injury, successful clinical translation has not been achieved. This study investigated whether drugs routinely used in clinical anesthesia influence cardioprotective effectiveness by reducing effects of reactive oxygen species (ROS), upstream triggers of cardioprotective signaling. Effects of propofol, sevoflurane, or remifentanil were compared on postischemic functional recovery induced by ROS-mediated postconditioning with Intralipid. METHODS: Recovery of left ventricular (LV) work, an index of IR injury, was measured in isolated Sprague-Dawley rat hearts subjected to global ischemia (20 minutes) and reperfusion (30 minutes). Hearts were either untreated or were treated with postconditioning with Intralipid (1%, throughout reperfusion). Propofol (10 μM), sevoflurane (2 vol%), remifentanil (3 nM), or combinations thereof were administered peri-ischemically (before and during IR). The effects of anesthetics on ROS production were measured in LV cardiac fibers by Amplex Red assay under phosphorylating and nonphosphorylating conditions. RESULTS: Recovery of LV work (expressed as percentage of the preischemic value ± standard deviation) in untreated hearts was poor (20% ± 7%) and was improved by Intralipid postconditioning (58% ± 8%, P = .001). In the absence of Intralipid postconditioning, recovery of LV work was enhanced by propofol (28% ± 9%, P = .049), sevoflurane (49% ± 5%, P

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You’re Wrong, I’m Right: Dueling Authors Reexamine Classic Teachings in Anesthesia

No abstract available

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Macintosh Blade Videolaryngoscopy Combined With Rigid Bonfils Intubation Endoscope Offers a Suitable Alternative for Patients With Difficult Airways

BACKGROUND: In the armamentarium of an anesthesiologist, videolaryngoscopy is a valuable addition to secure the airway. However, when the videolaryngoscope (VLS) offers no solution, few options remain. Earlier, we presented an intubation technique combining Macintosh blade VLS and Bonfils intubation endoscope (BIE) for a patient with a history of very difficult intubation. In the present study, we evaluated this technique to establish whether it is a valuable alternative. METHODS: In this single-blinded nonrandomized study, 38 patients with a history of difficult intubation or 1 or more predictors of difficult intubation, scoring a Cormack & Lehane (C&L) grade III or IV using Macintosh blade VLS, were included. Patients were intubated combining the VLS with the BIE. The C&L grade was scored 3 times during (1) direct laryngoscopy; (2) indirect videolaryngoscopy; and (3) using the combined technique (VLS + BIE). Afterward, 2 blinded anesthesiologists assessed the C&L grade using the pictures taken during the procedure. RESULTS: Data of 38 patients were analyzed. An improvement of the C&L grade with the combined technique occurred in 33 of 38 patients (86.8%; 95% confidence interval, 71.9%–95.6%). Reviewer 1 reported an improvement of the C&L grade with the combined technique in 37 of 38 patients. Reviewer 2 reported improvement in 33 and deterioration in 2 of the patients. No complications occurred. CONCLUSIONS: The combined use of a VLS with Macintosh blade and BIE gives the anesthesiologist a valuable alternative intubation option in patients with extremely difficult airways. Accepted for publication November 2, 2017. Funding: None of the study members has received funding from the device manufacturer of the Bonfils intubation endoscope. All devices used for the study were readily available from the department. No funding was obtained from the device manufacturers. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Clinical trial registration: ClinicalTrials.gov—NCT01691703. Reprints will not be available from the authors. Address correspondence to Barbe M. Pieters, MD, PhD, Department of Anesthesiology, University Medical Centre Utrecht, Postbus 85090, 3508 AB Utrecht, the Netherlands. Address e-mail to bmapieters@gmail.com. © 2017 International Anesthesia Research Society

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Impact of Inhalational Anesthetics on Liver Regeneration After Living Donor Hepatectomy: A Propensity Score-Matched Analysis

BACKGROUND: Although desflurane and sevoflurane, the most commonly used inhalational anesthetics, have been linked to postoperative liver injury, their impact on liver regeneration remains unclear. We compared the influence of these anesthetics on the postoperative liver regeneration index (LRI) after living donor hepatectomy (LDH). METHODS: We conducted a retrospective chart review of 1629 living donors who underwent right hepatectomy for LDH between January 2008 and August 2016. The patients were divided into sevoflurane (n = 1206) and desflurane (n = 423) groups. Factors associated with LRI were investigated using multivariable logistic regression analysis. Propensity score matching analysis compared early (1 postoperative week) and late (within 1–2 months) LRIs and delayed recovery of hepatic function between the 2 groups. RESULTS: The mean early and late LRIs in the 1629 patients were 63.3% ± 41.5% and 93.7% ± 48.1%, respectively. After propensity score matching (n = 403 pairs), there were no significant differences in early and late LRIs between the sevoflurane and desflurane groups (early LRI: 61.2% ± 41.5% vs 58.9% ± 42.4%, P = .438; late LRI: 88.3% ± 44.3% vs 94.6% ± 52.4%, P = .168). Male sex (regression coefficient [β], 4.6; confidence interval, 1.6–7.6; P = .003) and remnant liver volume (β, –4.92; confidence interval, –5.2 to –4.7; P

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Sources of Variation in Anesthetic Drug Costs

BACKGROUND:Increasing attention has been focused on health care expenditures, which include anesthetic-related drug costs. Using data from 2 large academic medical centers, we sought to identify significant contributors to anesthetic drug cost variation.METHODS:Using anesthesia information management systems, we calculated volatile and intravenous drug costs for 8 types of inpatient surgical procedures performed from July 1, 2009, to December 31, 2011. For each case, we determined patient age, American Society of Anesthesiologists (ASA) physical status, gender, institution, case duration, in-room provider, and attending anesthesiologist. These variables were then entered into 2 fixed-effects linear regression models, both with logarithmically transformed case cost as the outcome variable. The first model included duration, attending anesthesiologist, patient age, ASA physical status, and patient gender as independent variables. The second model included case type, institution, patient age, ASA physical status, and patient gender as independent variables. When all variables were entered into 1 model, redundancy analyses showed that case type was highly correlated (R2 = 0.92) with the other variables in the model. More specifically, a model that included case type was no better at predicting cost than a model without the variable, as long as that model contained the combination of attending anesthesiologist and case duration. Therefore, because we were interested in determining the effect both variables had on cost, 2 models were created instead of 1. The average change in cost resulting from each variable compared to the average cost of the reference category was calculated by first exponentiating the β coefficient and subtracting 1 to get the percent difference in cost. We then multiplied that value by the mean cost of the associated reference group.RESULTS:A total of 5504 records were identified, of which 4856 were analyzed. The median anesthetic drug cost was $38.45 (25th percentile = $23.23, 75th percentile = $63.82). The majority of the variation was not described by our models—35.2% was explained in the model containing case duration, and 32.3% was explained in the model containing case type. However, the largest sources of variation our models identified were attending anesthesiologist, case type, and procedure duration. With all else held constant, the average change in cost between attending anesthesiologists ranged from a cost decrease of $41.25 to a cost increase of $95.67 (10th percentile = −$19.96, 90th percentile = +$20.20) when compared to the provider with the median value for mean cost per case. The average change in cost between institutions was significant but minor ($5.73).CONCLUSIONS:The majority of the variation was not described by the models, possibly indicating high per-case random variation. The largest sources of variation identified by our models included attending anesthesiologist, procedure type, and case duration. The difference in cost between institutions was statistically significant but was minor. While many prior studies have found significant savings resulting from cost-reducing interventions, our findings suggest that because the overall cost of anesthetic drugs was small, the savings resulting from interventions focused on the clinical practice of attending anesthesiologists may be negligible, especially in institutions where access to more expensive drugs is already limited. Thus, cost-saving efforts may be better focused elsewhere. BACKGROUND: Increasing attention has been focused on health care expenditures, which include anesthetic-related drug costs. Using data from 2 large academic medical centers, we sought to identify significant contributors to anesthetic drug cost variation. METHODS: Using anesthesia information management systems, we calculated volatile and intravenous drug costs for 8 types of inpatient surgical procedures performed from July 1, 2009, to December 31, 2011. For each case, we determined patient age, American Society of Anesthesiologists (ASA) physical status, gender, institution, case duration, in-room provider, and attending anesthesiologist. These variables were then entered into 2 fixed-effects linear regression models, both with logarithmically transformed case cost as the outcome variable. The first model included duration, attending anesthesiologist, patient age, ASA physical status, and patient gender as independent variables. The second model included case type, institution, patient age, ASA physical status, and patient gender as independent variables. When all variables were entered into 1 model, redundancy analyses showed that case type was highly correlated (R2 = 0.92) with the other variables in the model. More specifically, a model that included case type was no better at predicting cost than a model without the variable, as long as that model contained the combination of attending anesthesiologist and case duration. Therefore, because we were interested in determining the effect both variables had on cost, 2 models were created instead of 1. The average change in cost resulting from each variable compared to the average cost of the reference category was calculated by first exponentiating the β coefficient and subtracting 1 to get the percent difference in cost. We then multiplied that value by the mean cost of the associated reference group. RESULTS: A total of 5504 records were identified, of which 4856 were analyzed. The median anesthetic drug cost was $38.45 (25th percentile = $23.23, 75th percentile = $63.82). The majority of the variation was not described by our models—35.2% was explained in the model containing case duration, and 32.3% was explained in the model containing case type. However, the largest sources of variation our models identified were attending anesthesiologist, case type, and procedure duration. With all else held constant, the average change in cost between attending anesthesiologists ranged from a cost decrease of $41.25 to a cost increase of $95.67 (10th percentile = −$19.96, 90th percentile = +$20.20) when compared to the provider with the median value for mean cost per case. The average change in cost between institutions was significant but minor ($5.73). CONCLUSIONS: The majority of the variation was not described by the models, possibly indicating high per-case random variation. The largest sources of variation identified by our models included attending anesthesiologist, procedure type, and case duration. The difference in cost between institutions was statistically significant but was minor. While many prior studies have found significant savings resulting from cost-reducing interventions, our findings suggest that because the overall cost of anesthetic drugs was small, the savings resulting from interventions focused on the clinical practice of attending anesthesiologists may be negligible, especially in institutions where access to more expensive drugs is already limited. Thus, cost-saving efforts may be better focused elsewhere. Accepted for publication November 8, 2017. Funding: Supported by departmental funding. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Jonathan P. Wanderer, MD, MPhil, The Vanderbilt Clinic, 1301 Medical Center Dr, Suite 4648, Nashville, TN 37232. Address e-mail to Jonathan.p.wanderer@vanderbilt.edu. © 2017 International Anesthesia Research Society

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Promoting a Restrictive Intraoperative Transfusion Strategy: The Influence of a Transfusion Guideline and a Novel Software Tool

BACKGROUND: The effect of neither transfusion guidelines nor decision support tools on intraoperative transfusion has been previously evaluated. The University of Michigan introduced a transfusion guideline in 2009, and in 2011, the Department of Anesthesiology developed a transfusion decision support tool. The primary aim of this study was to assess the associations of the transfusion guideline and the optional use of the software transfusion tool with intraoperative behaviors; pretransfusion hematocrit assessment (whether or not a hematocrit was checked before each red cell unit) and restrictive red cell use (withholding transfusion unless the hematocrit was ≤21%). METHODS: This was a before–after retrospective study without a concurrent control group of patients transfused 1–3 units of red cells intraoperatively. Three phases were studied to provide data both before and after the implementation of the transfusion guideline and the intraoperative software tool. Within each phase, trends of checking hematocrits before transfusion and restrictive transfusion were charted against time. F tests were used to measure differences of slopes. The difference between means of each phase was measured using Mann-Whitney U tests. Independent associations were measured using mixed-effects multivariable logistic regression. A secondary outcome analysis was conducted for 30-day mortality, myocardial infarction, renal injury, and their combination. RESULTS: The transfusion guideline was associated with increased pretransfusion hematocrit evaluation (67.4%, standard deviation [SD] 3.9 vs 76.5%, SD 2.7; P

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An Environment Is More Than a Climate

No abstract available

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Kras mutant genetically engineered mouse models of human cancers are genomically heterogeneous [Genetics]

KRAS mutant tumors are largely recalcitrant to targeted therapies. Genetically engineered mouse models (GEMMs) of Kras mutant cancer recapitulate critical aspects of this disease and are widely used for preclinical validation of targets and therapies. Through comprehensive profiling of exomes and matched transcriptomes of >200 KrasG12D-initiated GEMM tumors from one...

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Cloning and gene expression analysis of two cDNA of cysteine proteinase genes involved in programmed cell death in the inner integument from developing seeds of Jatropha curcas L

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Publication date: Available online 19 December 2017
Source:Gene Expression Patterns
Author(s): Antônio José Rocha, Simone Pohl, Cristiane Sá Roriz Fonteles
In this paper, two cysteine proteinases were cloned from Jatropha curcas seeds. The full length cDNAs obtained from cloning of Jc-CysEP1 and Jc-CysEP2 genes were 1.516bp and 1500 pb, respectively. The Jc-CysEP1 contained a 1083bp open reading frame (ORF) coding for 360 amino acids. The JcCysEP1 protein sequence had an estimated native molecular weight of 36.89 kDa, with a predicted isoelectric point of 4.55. The average lengths of JcCysEP1 5′ UTR and 3′ UTR were 269 bp and 167bp, respectively. The Jc-CysEP2 contained a 1077 pb open reading frame (ORF) that encoded 358 amino acids. We also identified UTRs with lengths of 229 pb (5′UTR) and 194 pb (3′UTR). The Jc-CysEP2 sequence had a native molecular weight of 39.94 kDa, with a predicted isoelectric point of 6.19. Real-time PCR analyses of developing seeds (stages I-VII) showed that most cysteine proteinase genes were expressed at stage IV (middle stage) revealing peculiar spatio-temporal differences. JcCysEP2 was the cysteine proteinase gene with the highest expression in inner integument tissue, while JcCysEP1 was expressed in lower levels. Our results suggest that JcCysEP2 could be the major cysteine proteinase gene involved in PCD events in inner integument tissue, playing a critical role in PCD events during seed development, while Jc-CyEP1 and JcCysEP2 genes act cooperatively in stages IV-VII. JcCysEP2 is important to complete their participation in PCD until development of seeds.



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Application of Next-Generation Sequencing (NGS) to improve cancer management: A review of the clinical effectiveness and cost-effectiveness

Abstract

Uptake of Next-Generation Sequencing (NGS) has increased dramatically due to significant cost reductions and broader community acceptance of NGS. To systematically review the evidence on both the clinical effectiveness and the cost-effectiveness of applying NGS to cancer care. A systematic search for full-length original research articles on the clinical effectiveness and cost-effectiveness of NGS in MEDLINE and EMBASE. Articles that focussed on cancer care and involved the application of NGS were included for the review of clinical effectiveness. For the cost-effectiveness review, we only included the articles with economic evaluations of NGS in cancer care. We report the rate of successfully detecting mutations from the clinical studies. The Incremental Cost-Effectiveness Ratio and sensitivity analysis outcomes are reported for the cost-effectiveness articles. Fifty-six articles reported that sequencing patient samples using targeted gene panels, and 83% of the successfully sequenced patients harboured at least one mutation. Only six studies reported on the cost-effectiveness of the application of NGS in cancer care. NGS is an effective tool for identifying mutation in cancer patients. However, more rigorous cost-effectiveness studies of NGS applied to cancer management are needed to determine whether NGS can improve patient outcomes cost-effectively.

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Manifestation of recessive combined D-2-, L-2-hydroxyglutaric aciduria in combination with 22q11.2 deletion syndrome

22q11.2 deletion syndrome is one of the most common human microdeletion syndromes. The clinical phenotype of 22q11.2 deletion syndrome is variable, ranging from mild to life-threatening symptoms, depending mainly on the extent of the deleted region. Brain malformations described in association with 22q11.2 deletion syndrome include polymicrogyria, cerebellar hypoplasia, megacisterna magna, and agenesis of the corpus callosum (ACC), although these are rare. We report here for the first time a patient who manifested combined D-2- and L-2-hydroxyglutaric aciduria as a result of a hemizygous mutation in SLC25A1 in combination with 22q11.2 deletion. The girl was diagnosed to have ACC shortly after birth and a deletion of 22q11.2 was identified by genetic analysis. Although the patient showed cardiac anomalies, which is one of the typical symptoms of 22q11.2 deletion syndrome, her rather severe phenotype and atypical face prompted us to search for additional pathogenic mutations. Three genes present in the deleted 22q11.2 region, SLC25A1, TUBA8, and SNAP29, which have been reported to be associated with brain malformation, were analyzed for the presence of pathogenic mutations. A frameshift mutation, c.18_24dup (p.Ala9Profs*82), was identified in the first exon of the remaining SLC25A1 allele, resulting in the complete loss of normal SLC25A1 function in the patient's cells. Our results support the notion that the existence of another genetic abnormality involving the retained allele on 22q11.2 should be considered when atypical or rare phenotypes are observed.



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Identification of differentially expressed genes in longissimus dorsi muscle between Wei and Yorkshire pigs using RNA sequencing

Abstract

Intramuscular fat (IMF) content is an important trait closely related to meat quality, which is highly variable among pig breeds from diverse genetic backgrounds. High-throughput sequencing has become a powerful technique for analyzing the whole transcription profiles of organisms. In order to elucidate the molecular mechanism underlying porcine meat quality, we adopted RNA sequencing to detect transcriptome in the longissimus dorsi muscle of Wei pigs (a Chinese indigenous breed) and Yorkshire pigs (a Western lean-type breed) with different IMF content. For the Wei and Yorkshire pig libraries, over 57 and 64 million clean reads were generated by transcriptome sequencing, respectively. A total of 717 differentially expressed genes (DEGs) were identified in our study (false discovery rate < 0.05 and fold change > 2), with 323 up-regulated and 394 down-regulated genes in Wei pigs compared with Yorkshire pigs. Gene Ontology analysis showed that DEGs significantly related to skeletal muscle cell differentiation, phospholipid catabolic process, and extracellular matrix structural constituent. Pathway analysis revealed that DEGs were involved in fatty acid metabolism, steroid biosynthesis, glycerophospholipid metabolism, and protein digestion and absorption. Quantitative real time PCR confirmed the differential expression of 11 selected DEGs in both pig breeds. The results provide useful information to investigate the transcriptional profiling in skeletal muscle of different pig breeds with divergent phenotypes, and several DEGs can be taken as functional candidate genes related to lipid metabolism (ACSL1, FABP3, UCP3 and PDK4) and skeletal muscle development (ASB2, MSTN, ANKRD1 and ANKRD2).



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Fine mapping and candidate gene analysis of the quantitative trait locus gw8.1 associated with grain length in rice

Abstract

A quantitative trait locus (QTL) gw8.1 was detected in the population derived from a cross between the elite japonica cultivar, 'Hwaseong' and Oryza rufipogon (IRGC 105491). Near isogenic lines (NILs) harboring the O. rufipogon segment on chromosome 8 showed increased grain length and weight compared to those of the recurrent parent, Hwaseong. This QTL was mapped to a 175.3-kb region containing 28 genes, of which four were considered as candidates based on the presence of mutations in their coding regions and as per the RNA expression pattern during the inflorescence stage. Leaves and panicles obtained from plants harvested 5 days after heading showed differences in gene expression between Hwaseong and gw8.1-NILs. Most genes were upregulated in O. rufipogon and gw8.1-NIL than in Hwaseong. Scanning electron microscopy analysis of the lemma inner epidermal cells indicated that cell length was higher in gw8.1 NIL than in Hwaseong, indicating that gw8.1 might regulate cell elongation. Among the candidate genes, LOC_Os08g34380 encoding a putative receptor-like kinase and LOC_Os08g34550 encoding putative RING-H2 finger protein were considered as possible candidates based on their functional similarity.



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Issue Information - Editorial Board



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The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome

RNU4ATAC pathogenic variants to date have been associated with microcephalic osteodysplastic primordial dwarfism, type 1 and Roifman syndrome. Both conditions are clinically distinct skeletal dysplasias with microcephalic osteodysplastic primordial dwarfism, type 1 having a more severe phenotype than Roifman syndrome. Some of the overlapping features of the two conditions include developmental delay, microcephaly, and immune deficiency. The features also overlap with Lowry Wood syndrome, another rare but well-defined skeletal dysplasia for which the genetic etiology has not been identified. Characteristic features include multiple epiphyseal dysplasia and microcephaly. Here, we describe three patients with Lowry Wood syndrome with biallelic RNU4ATAC pathogenic variants. This report expands the phenotypic spectrum for biallelic RNU4ATAC disorder causing variants and is the first to establish the genetic cause for Lowry Wood syndrome.



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