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Genetic variation in ANGPTL4 is associated with lipid traits. Here, the authors find that predicted loss-of-function variants in ANGPTL4 are associated with glucose homeostasis and reduced risk of type 2 diabetes and that Angptl4 −/− mice on a high-fat diet show improved insulin sensitivity.

Background Prior studies have shown that women have worse 3‐month survival after receiving a left ventricular assist device compared with men. Currently used prognostic scores, including the Heartmate II Risk Score, do not account for the increased residual risk in women. We used the IMACS (International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support) registry to create and validate a sex‐specific risk score for early mortality in left ventricular assist device recipients. Methods and Results Adult patients with a continuous‐flow LVAD from the IMACS registry were randomly divided into a derivation cohort (DC; n=9113; 21% female) and a validation cohort (VC; n=6074; 21% female). The IMACS Risk Score was developed in the DC to predict 3‐month mortality, from preoperative candidate predictors selected using the Akaike information criterion, or significant sex × variable interaction. In the DC, age, cardiogenic shock at implantation, body mass index, blood urea nitrogen, bilirubin, hemoglobin, albumin, platelet count, left ventricular end‐diastolic diameter, tricuspid regurgitation, dialysis, and major infection before implantation were retained as significant predictors of 3‐month mortality. There was significant ischemic heart failure × sex and platelet count × sex interaction. For each quartile increase in IMACS risk score, men (odds ratio [OR], 1.86; 95% CI, 1.74–2.00; P

Widely coexpressed Src family kinase (SFK) members Src, Fyn and Yes are involved in various cellular events, often acting downstream of receptor tyrosine kinases, such as vascular endothelial growth factor (VEGF) receptors. They are well known for their functional redundancy; any unique features remain largely undefined. Utilizing RNA interference, we have selectively knocked down Src, Fyn and Yes in human retinal microvascular endothelial cells (HRMECs). Cells with single SFK knockdown showed that all three kinases were required for VEGF mitogenic signaling. VEGF-induced cell migration was significantly increased in Fyn-deficient cells and decreased in Yes-deficient cells. Selective interference of Fyn, but not Src or Yes, impaired VEGF-induced tube formation in HRMECs. Cells in which all three SFKs were targeted showed significant inhibition of all three cellular events. In addition, interference of Src, Fyn and Yes did not affect the anti-apoptotic effect of VEGF in HRMECs, as determined by DNA fragmentation analysis. These results provide direct evidence that Src, Fyn and Yes maintain distinct properties in the regulation of VEGF-mediated endothelial cell events. [ABSTRACT FROM AUTHOR]

Substance Use Disorder (SUD) is a major public health concern affecting an estimated 22.5 million individuals in the United States. The primary aim of this study was to characterize psychological pain in a cohort of patients participating in outpatient treatment for SUD. A secondary aim was to determine the relationships between pre-treatment assessments of psychological pain, depression, anxiety and hopelessness with treatment retention time and completion rates. Data was analyzed from 289 patients enrolled in an outpatient community drug treatment clinic in Southern California, U.S. A previously determined threshold score on the Mee-Bunney Psychological Pain Assessment Scale (MBP) was utilized to group patients into high and low-moderate scoring subgroups. The higher pain group scored higher on measures of anxiety, hopelessness and depression compared to those in the low-moderate pain group. Additionally, patients scoring in the higher psychological pain group exhibited reduced retention times in treatment and more than two-fold increased odds of dropout relative to patients with lower pre-treatment levels of psychological pain. Among all assessments, the correlation between psychological pain and treatment retention time was strongest. To our knowledge, this is the first study to demonstrate that psychological pain is an important construct which correlates with relevant clinical outcomes in SUD. Furthermore, pre-treatment screening for psychological pain may help target higher-risk patients for clinical interventions aimed at improving treatment retention and completion rates.

This paper presents the evaluation of novel electrodes for surface electromyography (sEMG) measurements. The electrodes are based on the mixture of carbon powder, quaternary salt, and viscoelastic polymeric adhesive (carbon/salt/adhesive or simply CSA), which when combined, provide the unique advantages of having longer (theoretically infinite) shelf life and potentially lower cost than Ag/AgCl hydrogel electrodes, consistent with FLEXcon's Patent #8 673 184. The 20 subjects were recruited to collect simultaneous recordings of sEMG signals using Ag/AgCl and CSA electrodes, side-by-side on triceps brachii, tibial anterior muscles, biceps brachii, and quadriceps femoris. Although CSA sEMG electrodes showed higher electrode-skin contact impedance for the frequency range of 4 Hz-2 kHz, no significant differences were found in the signals' amplitude between the two electrodes either during relaxation or contraction stages. Furthermore, correlations of the computed linear envelopes (>0.91), rms value envelopes (>0.91), and power spectral densities (>0.95) of the signals were found to be high between the two media. Detected ON- and OFF-times of contraction were also highly correlated (>0.9) and interchangeable (ON-time: bias = -0.02, variance = 0.11; OFF-time: bias = -0.04, variance = 0.23) between the two media. However, CSA sEMG electrodes exhibited a significantly better response to noise (38.3 ± 10.6 dB versus 32.7 ± 15.6 dB) and motion artifacts (24.1 ± 12.1 dB versus 16.6 ± 8.52 dB), and a significantly lower spectral deformation (1.32 ± 0.2 versus 1.46 ± 0.4). Ag/AgCl electrodes showed a significantly more peaked and sensitive response to EMG amplitude (67.9 ± 13.9 dB versus 65.4 ± 14.6 dB). Given no significant differences in many of the measures described earlier and the fact that CSA electrodes have an infinite shelf-life are potentially lower cost, and are more resistant to motion artifacts, the new electrodes provide an attractive alternative to Ag/AgCl electrodes for sEMG measurements.

Pregabalin is gaining popularity in the perioperative period for its usefulness in treating neuropathic pain and its apparent opioid-sparing effect. The present report describes the perioperative course of three patients who received pregabalin and experienced significant respiratory depression in the postoperative period. All three patients consented to the report and publication of the present case series. The first patient was elderly with borderline renal dysfunction. She experienced respiratory arrest in the immediate postoperative period following a craniotomy for tumour excision. The second patient presented with severe respiratory depression 12 h after receiving a spinal anesthetic for joint replacement, and was later found to have clinically significant obstructive sleep apnea. The third patient, who was an otherwise healthy elderly individual on benzodiazepines for anxiety, experienced respiratory arrest in the postanesthesia care unit after an uneventful anesthesia for lumbar spine decompression. All of these patients were treated successfully with standard resuscitation measures. Although other causes of respiratory depression in these patients were considered, there appears to be an association between pregabalin and this complication. The present article briefly reviews the evidence regarding the perioperative use of pregabalin. Based on the authors’ experience and the available evidence, they believe that pregabalin may be useful in the management of acute pain in carefully selected patients undergoing certain surgeries. A clinical algorithm has been developed to guide the perioperative use of pregabalin. This algorithm may be helpful in increasing the safety of perioperative pregabalin use.

The Canadian Collaborative Acute Pain Initiative, established in 2002, is a voluntary, multidisciplinary consortium of acute pain health professionals from across Canada whose goal is to improve acute pain management through discussion and consensus. The group met in January 2002 to define strategic areas related to the treatment of acute pain. The areas identified were: the definition of pain; the epidemiology of pain; the concept of an 'ideal' acute pain management service; education; therapeutic options; symptom management; and research and safety. In November 2002, a second meeting was held to develop objectives and recommendations for the management of acute pain based on the defined areas. The outcome of these discussions is summarized in this paper.

To explore factors associated with occupational sex segregation in the United States over the past four decades, we analyzed U.S. Bureau of Labor Statistics data for the percent of women employed in 60 varied occupations from 1972 to 2010. Occupations were assessed on status, people-things orientation, and data-ideas orientation. Multilevel linear modeling (MLM) analyses showed that women increasingly entered high-status occupations from 1972 to 2010, but women's participation in things-oriented occupations (e.g., STEM fields and mechanical and construction trades) remained low and relatively stable. Occupations' data-ideas orientation was not consistently related to sex segregation. Because of women's increased participation in high-status occupations, occupational status became an increasingly weak predictor of women's participation rates in occupations, whereas occupations' people-things orientation became an increasingly strong predictor over time. These findings are discussed in relation to theories of occupational sex segregation and social policies to reduce occupational sex segregation.

Abstract A comprehensive understanding of pain pathophysiology is fundamental to pain assessment and management. However, this is a complex topic and one often difficult to grasp from two-dimensional images in books or presentations. Managing Pain Together: The Pathophysiology of Pain, a bilingual, interactive web-based module, provides a dynamic, interactive approach to understanding the pathophysiology of pain for medical students, physicians, and nurses. The module illustrates the basic ascending pain pathways, as well as the descending pain-modulating pathways through clear interactive images. The four dimensions of pain are explained by pain experts through video. For each dimension, individual differences are addressed and the role of drugs and other pain management approaches are discussed using a combination of text, images, and animations. Pain phenomena that are not explained through the basic pathways of pain transmission are considered: How do we explain severe pain when only minor trauma exists? Or no pain but severe trauma? How do we explain chronic pain that persists long after the initial tissue trauma has appeared to have healed? The module can be integrated into a medical education curriculum or used independently as a learning and revision aid. It is self-explanatory to use as it is learner-centered and self-paced. It is estimated that it will take learners 30–45 minutes to complete. There is no need for a facilitator to preparare ahead of time for implementation. This resource is part of the University of Ottawa undergraduate medical education curriculum and the online Managing Pain Together program. It is accessible to users at no cost at anytime from anywhere they have access to an Internet connection. A preliminary evaluation by second-year medical students indicated that students loved the use of video, audio, and graphic technology.