Global Research Highlights

Editor's note: Annals has partnered with a small group of selected journals of international emergency medicine societies to share from each a highlighted research study, as selected monthly by their editors. Our goals are to increase awareness of our readership to research developments in the international emergency medicine literature, promote collaboration among the selected international emergency medicine journals, and support the improvement of emergency medicine world-wide, as described in the WAME statement at http://ift.tt/2dmKsCb.

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Calendar

▮ Symposium by the Sea 2017. August 3-6, 2017. Boca Raton, FL. Contact: Evan Buckley. Email: ebuckley@emlrc.org. Url: http://ift.tt/2rPrjnk. (14.8)

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What's Coming in Annals ● July 2017

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76-Year-Old Man With Palpitations

A 76-year-old male physician with a history of hypertension and hypercholesterolemia presented to the emergency department (ED) with palpitations and diaphoresis that began while watching the first 2016 presidential debate. He measured his pulse at 150 beats/min and self-administered 2 doses of propranolol 10 mg during a 3-and-a-half-hour period, without improvement. On arrival to the ED, his pulse rate had slowed to 120 beats/min, as shown in Figure 1. The initial troponin I level was 0.04 ng/mL.

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Antibiotics Only for Appendicitis?

SEE RELATED ARTICLE, P. 1.

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Nonoperative Management of Appendicitis: A Paradigm Shift?

The concept that adult patients with acute appendicitis may be discharged from the emergency department (ED) with a prescription for antibiotics is an important potential practice change for emergency medicine and surgery.

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Alternative Methods to Vascular Access in the Emergency Department

There are situations in the emergency department in which intravenous access procedures fail or are insufficient to meet the clinical needs of the patient. Alternative access methods must be available under such circumstances, and their usage should be a part of the emergency medicine practice privileges. These alternate access modalities include, but are not limited to, intraosseous lines, external jugular lines, central lines, and peripheral lines placed under the guidance of ultrasonographic or illumination devices.

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Prevalence of Pelvic Inflammatory Disease in Sexually Experienced Women of Reproductive Age—United States, 2013-2014

[Kreisel K, Torrone E, Bernstein K, et al. Prevalence of pelvic inflammatory disease in sexually experienced women of reproductive age—United States, 2013-2014. MMWR Morb Mortal Wkly Rep. 2017;66:80–83.]

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Male Infant With Rapidly Progressive Skin Lesions

A 7-month-old male infant presented with fever for 2 days and rash for 1 day. The patient had received a diagnosis of croup 1 week before admission. Physical examination revealed hypotension and purpuric lesions with surrounding erythema over the right thigh and buttock (Figure 1). Laboratory testing revealed anemia, neutropenia, and hyponatremia. The buttock lesion evolved into a gangrenous eschar with a central dusky necrosis, followed by a surrounding halo 12 hours later (Figure 2).

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Editors

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Table of Contents

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Urgent Care Centers

An urgent care center is a walk-in clinic focused on the delivery of medical care for minor illnesses and injuries in an ambulatory medical facility outside of a traditional hospital-based or freestanding emergency department (ED). Other names for similar types of facilities include, but are not limited to, after-hours walk-in clinics, minute clinics, quick care clinics, minor emergency centers, and minor care clinics. In some instances, facilities have used the term "emergency" in their name or advertisements; for example, "Minor Emergency Clinic" or "We Treat Emergencies."

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Commentary

Although the estimated incidence of PID is decreasing,1 the prevalence of self-reported lifetime PID of 4.4% noted in the latest Centers for Disease Control and Prevention (CDC) survey implies that 2.5 million women of reproductive age in this country have had PID. Because many of these patients can be expected to have significant morbidity related to pain, infertility, and ectopic pregnancy, the burden of PID remains very high.2 Thus, emergency physicians should follow the CDC STI screening recommendations and screen sexually active female patients younger than 25 years for chlamydia and gonorrhea.

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Guidelines for Emergency Physicians on the Interpretation of Physician Orders for Life-Sustaining Therapy (POLST)

The ethical principle of respect for patient autonomy and the legal principle of patient self-determination give individuals the right to make their own health care decisions. Advance directives and do-not-resuscitate documents were designed to allow people the opportunity to express their treatment preferences for situations when they cannot communicate those preferences themselves. Unfortunately, clinicians may not be able to honor those wishes because the documents are either unavailable or the wording is too vague or value based to apply to specific conditions encountered.

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In reply:

The comments we received in response to the supplement chapter "Blast Physics and Pathophysiology"1 are much appreciated. We also appreciate and recognize the commenter's significant contributions to the subject matter.

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Classified 2017 Advertising Rates & Information

Ads and complete payments must be received in writing by the issue's deadline date. These deadlines apply to insertions, cancellations, and changes.

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Role of the State EMS Medical Director

Joint Statement by the American College of Emergency Physicians (ACEP), the National Association of EMS Physicians (NAEMSP), and the National Association of State EMS Officials (NASEMSO)

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Classified

COLORADO, Colorado Springs: Yes! There is a great job available in Colorado! Independent, democratic group is expanding and in need of a few BC/BE emergency physicians. For more information contact Bill Kimble, MD at kimbles01@hotmail.com.

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Code of Ethics for Emergency Physicians

The basic professional obligation of beneficent service to humanity is expressed in various physicians' oaths and codes of ethics. In addition to this general obligation, emergency physicians accept specific ethical obligations that arise out of the unique features of emergency medical practice. The principles listed below express fundamental moral responsibilities of emergency physicians.

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Screening Questions at Triage

Triage is a rapid evaluation of patient acuity for the purpose of establishing the order or the location in which the patient should be treated by an emergency care provider and may be bypassed when patient care space and staff are immediately available. Optimal patient care occurs when the time between the patient's presentation and treatment by an emergency care provider is as short as possible.

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Investigation of Two Prototypes of Novel Noncontact Technologies for Automated Real-Time Capture of Incremental Drug Administration Data From Syringes.

BACKGROUND: An ideal electronic anesthesia recording system would be capable of not only recording physiological data but also injectable drug doses given, including those given incrementally from one syringe, without recourse to manual data entry. We compared 2 prototype devices which wirelessly recognized individual syringes and measured changes in their plunger positions via 2 different optical noncontact means, allowing calculation of incremental drug doses given. METHODS: Both devices incorporated a radio-frequency identification reader, which wirelessly read a unique code from a radio-frequency identification tag within syringe drug labels. A custom-designed cradle oriented any inserted 1-mL to 20-mL syringe in a repeatable position. The "laser" device had a moving laser beam broken by the end of the syringe plunger. The infrared (IR) device measured time of travel of IR light from a sender to a syringe plunger and back to a receiver. Both devices could therefore determine the drug and volume administered since the previous occasion when any syringe had been used. For each syringe size of 1, 2, 5, 10, and 20 mL, 121 plunger-length measurements were made over their full range, with each machine against a reference method of water filling and weighing using a randomized de Bruijn sequence. RESULTS: For every syringe size, the laser device showed greater accuracy and precision, lower bias, and narrower limits of agreement (95% confidence intervals = bias +/- 1.96 SD) than the IR device when compared to the reference method. For all syringe sizes, the range of bias was -0.05 to 0.32 mL for the laser and -2.42 to 1.38 mL for the IR. Lin concordance correlation coefficient values for the IR versus reference methods ranged from 0.6259 to 0.9255, with the lowest coefficients seen in syringes with the shortest distance of plunger travel (2 and 5 mL), while in laser versus reference comparisons, these coefficients were similar (0.9641-0.9981) over all syringe lengths. CONCLUSIONS: Both devices measured syringe volume changes, demonstrating potential for measuring incremental drug doses, recording these, and also the time of each measurement. The IR device had no moving parts, which would be advantageous in a clinical situation. However, the current embodiment was not deemed accurate enough for clinical use, potentially remediable through improvements in hardware and software design. The laser device showed high accuracy and precision over all syringe sizes and contained volumes, and was considered potentially accurate enough for clinical use with suitable development. (C) 2017 International Anesthesia Research Society

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Respiratory System Mechanics During Low Versus High Positive End-Expiratory Pressure in Open Abdominal Surgery: A Substudy of PROVHILO Randomized Controlled Trial.

BACKGROUND: In the 2014 PROtective Ventilation using HIgh versus LOw positive end-expiratory pressure (PROVHILO) trial, intraoperative low tidal volume ventilation with high positive end-expiratory pressure (PEEP = 12 cm H2O) and lung recruitment maneuvers did not decrease postoperative pulmonary complications when compared to low PEEP (0-2 cm H2O) approach without recruitment breaths. However, effects of intraoperative PEEP on lung compliance remain poorly understood. We hypothesized that higher PEEP leads to a dominance of intratidal overdistension, whereas lower PEEP results in intratidal recruitment/derecruitment (R/D). To test our hypothesis, we used the volumedependent elastance index %E2, a respiratory parameter that allows for noninvasive and radiation-free assessment of dominant overdistension and intratidal R/D. We compared the incidence of intratidal R/D, linear expansion, and overdistension by means of %E2 in a subset of the PROVHILO cohort. METHODS: In 36 patients from 2 participating centers of the PROVHILO trial, we calculated respiratory system elastance (E), resistance (R), and %E2, a surrogate parameter for intratidal overdistension (%E2 > 30%) and R/D (%E2

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Pupillary Unrest: Is It a Generalizable Finding?.

No abstract available

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False Low ETCO2 Measurements From Carbon Dioxide Sampling Nasal Cannula and How to Correct the Situation.

No abstract available

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Epidemiologic Analysis of Elective Operative Procedures in Infants Less Than 6 Months of Age in the United States.

BACKGROUND: This study uses publicly available data to analyze the total number of elective, potentially deferrable operative procedures involving infants

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In Response.

No abstract available

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A Descriptive Survey of Anesthesiology Residency Simulation Programs: How Are Programs Preparing Residents for the New American Board of Anesthesiology APPLIED Certification Examination?.

BACKGROUND: Anesthesiology residency programs may need new simulation-based programs to prepare residents for the new Objective Structured Clinical Examination (OSCE) component of the American Board of Anesthesiology (ABA) Primary Certification process. The design of such programs may require significant resources, including faculty time, expertise, and funding, as are currently needed for structured oral examination (SOE) preparation. This survey analyzed the current state of US-based anesthesiology residency programs regarding simulation-based educational programming for SOE and OSCE preparation. METHODS: An online survey was distributed to every anesthesiology residency program director in the US. The survey included 15 to 46 questions, depending on each respondent's answers. The survey queried current practices and future plans regarding resident preparation specifically for the ABA APPLIED examination, with emphasis on the OSCE. Descriptive statistics were summarized. [chi]2 and Fisher exact tests were used to test the differences in proportions across groups. Spearman rank correlation was used to examine the association between ordinal variables. RESULTS: The responding 66 programs (49%) were a representative sample of all anesthesiology residencies (N = 136) in terms of geographical location ([chi]2 P = .58). There was a low response rate from small programs that have 12 or fewer clinical anesthesia residents. Ninety-one percent (95% confidence interval [95% CI], 84% -95%) of responders agreed that it is the responsibility of the program to specifically prepare residents for primary certification, and most agreed that it is important to practice SOEs (94%; 95% CI, 88%-97%) and OSCEs (89%; 95% CI, 83%-94%). While 100% of respondents reported providing mock SOEs, only 31% (95% CI, 24%-40%) of respondents provided mock OSCE experiences. Of those without an OSCE program, 75% (95% CI, 64%-83%) reported plans to start one. The most common reasons for not having an OSCE program already in place, and the perceived challenges for implementing an OSCE program, were the same: lack of time (faculty and residents), expertise in OSCE development and assessment, and funding. CONCLUSIONS: The results provide data from residency programs for benchmarking their simulation curriculum and ABA APPLIED Examination preparation offerings. Despite agreement that residency programs should prepare residents for the ABA APPLIED Examination, many programs have yet to implement an OSCE preparation program, in part due to lack of financial resources, faculty expertise, and time. Additionally, in contrast to the SOE, the OSCE is a new format for ABA primary certification. As a result, the lack of consensus concerning preparation needs could be related to the amount information that is available regarding the examination content and assessment process. (C) 2017 International Anesthesia Research Society

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Postpartum Tubal Sterilization: Making the Case for Urgency.

The parturient who requests postpartum sterilization has given consideration to and has made decisions regarding this aspect of her medical care long before her delivery. She arrives at parturition expecting the postpartum procedure to be performed as intended. The American Congress of Obstetricians and Gynecologists has reaffirmed its opinion that postpartum sterilization is an urgent procedure, owing to the safety and superior effectiveness of tubal sterilization via minilaparotomy in the immediate postpartum period, and the adverse consequences for mothers, babies, and society when the procedure is not actualized as desired and intended. In contrast, recent practice guidelines for obstetric anesthesia address anesthetic procedural aspects and short-term safety but overlook the long-term complications and considerations associated with failure to perform postpartum sterilization as planned. In practice, procedure completion rates are strikingly low, reportedly ranging from 31% to 52%. Reasons for failure to complete abound and include inadequate resources or inavailability of necessary personnel; obstetrician reluctance due to concerns for patient regret in younger women or medical comorbidities; barriers related to provision of obstetric care in a religiously affiliated hospital, or incomplete, improperly completed, or unavailable original federal consent forms among Medicaid-insured women. The federal requirement to wait 30 days after signing informed consent, and to retain the original signed document to be physically verified at time of the procedure, serves as a significant source of health care disparity for Medicaid-dependent mothers. This article reviews these larger issues of maternal health and comprehensive maternal care to broaden the anesthesiologist's appreciation of major benefits and potential risks of postpartum sterilization, including long-term effects, to promote an evidence-based, informed, and proactive role in delivering equitable, safe, and optimal care for these patients. (C) 2017 International Anesthesia Research Society

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Administration of Tetrahydrobiopterin (BH4) Protects the Renal Microcirculation From Ischemia and Reperfusion Injury.

BACKGROUND: Abdominal aortic aneurysm surgery with suprarenal cross-clamping is often associated with renal injury. Although the mechanism underlying such injury is unclear, tissue ischemia and reperfusion, which induces endothelial dysfunction and decreases the availability of tetrahydrobiopterin (BH4), may play a role. We evaluated whether BH4 administration prevents renal ischemia/reperfusion injury in an animal model of aortic cross-clamping. METHODS: Nineteen anesthetized, mechanically ventilated, and invasively monitored adult sheep were randomized into 3 groups: sham animals (n = 5) that underwent surgical preparation but no aortic clamping; an ischemia/reperfusion group (n = 7), where the aorta was clamped above the renal arteries for 1 hour, and a BH4 group (n = 7), in which animals received 20 mg/kg of BH4 followed by aortic cross-clamp for 1 hour. Animals were followed for a maximum of 6 hours after reperfusion. The renal microcirculation was evaluated at baseline (before clamping), and 1, 4, and 6 hours after reperfusion using side-stream dark field videomicroscopy. The renal lactate-to-pyruvate ratio was evaluated using microdialysis. The primary outcome was the change in proportion of small perfused vessels before and after injury. Secondary outcomes were renal tissue redox state and renal function. RESULTS: Ischemia/reperfusion injury was associated with increases in heart rate and mean arterial pressure, which were blunted by BH4 administration. From the first to the sixth hour after reperfusion, the small vessel density (estimated mean difference [EMD], 1.03; 95% confidence interval [CI], 0.41-1.64; P = .003), perfused small vessel density (EMD, 0.84; 95% CI, 0.29-1.39; P = .005), and proportion of perfused small vessels (EMD, 8.60; 95% CI, 0.85-16.30; P = .031) were altered less in the BH4 than in the ischemia/reperfusion group. The renal lactate-to-pyruvate ratios were lower in the cortex in the BH4 than in the ischemia/reperfusion group from the first to the sixth hour after reperfusion (EMD, -19.16; 95% CI, -11.06 to 33.16; P = .002) and in the medulla from the first to the fourth hour (EMD, -26.62; 95% CI, -18.32 to 38.30; P = .020; and EMD, -8.68; 95% CI, -5.96 to 12.65; P = .019). At the sixth hour, serum creatinine was lower in the BH4 than in the ischemia/reperfusion group (EMD, -3.36; 95% CI, -0.29 to 1.39; P = .026). CONCLUSIONS: In this sheep model of renal ischemia/reperfusion, BH4 pretreatment reduced renal microvascular injury and improved renal metabolism and function. Further work is needed to clarify the potential role of BH4 in ischemia/reperfusion injury. (C) 2017 International Anesthesia Research Society

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Perioperative Surgical Home: Evaluation of a New Protocol Focused on a Multidisciplinary Approach to Manage Children Undergoing Posterior Spinal Fusion Operation.

BACKGROUND: The concept of Perioperative Surgical Home has been gaining significant attention in surgical centers. This model is delivering and improving coordinated care in a cost-effective manner to patients undergoing surgical procedures. It starts with the decision for surgical intervention, continues to the intraoperative and postoperative periods, and follows into long-term recovery. Constant re-evaluation of outcomes and modifications of delivery provides a feedback loop for improvement. Children's Hospital Los Angeles initiated a new protocol in June 2014 to manage children undergoing Posterior Spinal Fusion (PSF) with the goal to improve patient experience and lower the hospital length of stay and cost. METHODS: A retrospective chart review identified patients who underwent a PSF for idiopathic scoliosis before and after initiation of a new treatment protocol designed by a team of anesthesiologists, surgeons, nurses, and physical therapists. The new protocol included preoperative teaching of parents and patients, intraoperative anesthetic and surgical management, and immediate to long-term postoperative medical management. In addition to demographics, we examined length of stay, cost of hospitalization, pain scores on discharge, length of patient-controlled analgesia use, time to first solid food intake, and time to ambulation. RESULTS: Thirty-six patients were identified preinitiation and postinitiation of the protocol (total n = 72). There was no statistically significant difference in age, sex, use of intrathecal morphine, or estimated blood loss. Patients enrolled in the new protocol had higher American Society of Anesthesiologists classification (P = .003), significantly lower duration of patient-controlled analgesia use, time to first solid food intake, and time to ambulation (P= .001). The pain scores were higher at the time of discharge, although the difference was not statistically significant. Length of stay was significantly shorter in the new protocol group (P = .001), accounting for $292,560 in cost savings for the hospital. CONCLUSIONS: These data show that the cooperation of different teams in designing new management guidelines for patients requiring a PSF can significantly decrease the total length of stay and cost of hospitalization without altering quality of care. (C) 2017 International Anesthesia Research Society

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Platelet Counts and Postoperative Stroke After Coronary Artery Bypass Grafting Surgery.

BACKGROUND: Declining platelet counts may reveal platelet activation and aggregation in a postoperative prothrombotic state. Therefore, we hypothesized that nadir platelet counts after on-pump coronary artery bypass grafting (CABG) surgery are associated with stroke. METHODS: We evaluated 6 130 adult CABG surgery patients. Postoperative platelet counts were evaluated as continuous and categorical (mild versus moderate to severe) predictors of stroke. Extended Cox proportional hazard regression analysis with a time-varying covariate for daily minimum postoperative platelet count assessed the association of day-to-day variations in postoperative platelet count with time to stroke. Competing risks proportional hazard regression models examined associations between day-to-day variations in postoperative platelet counts with timing of stroke (early: 0-1 days; delayed: >=2 days). RESULTS: Median (interquartile range) postoperative nadir platelet counts were 123.0 (98.0-155.0) x 109/L. The incidences of postoperative stroke were 1.09%, 1.50%, and 3.02% for platelet counts >150 x 109/L, 100 to 150 x 109/L, and 150 x 109/L. Importantly, such thrombocytopenia, defined as a time-varying covariate, was significantly associated with delayed (>=2 days after surgery; adjusted HR, 2.83; 95% CI, 1.48.5.41; P = .0017) but not early postoperative stroke. CONCLUSIONS: Our findings suggest an independent association between moderate to severe postoperative thrombocytopenia and postoperative stroke, and timing of stroke after CABG surgery. (C) 2017 International Anesthesia Research Society

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In Response.

No abstract available

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A Shared Opportunity for Improving Electronic Medical Record Data.

With the recent rapid adoption of electronic medical records (EMRs), studies reporting results based on EMR data have become increasingly common. While analyzing data extracted from our EMR for a retrospective study, we identified various types of erroneous data entries. This report investigates the root causes of the incompleteness, inconsistency, and inaccuracy of the medical records analyzed in our study. While experienced health information management professionals are well aware of the many shortcomings with EMR data, the aims of this case study are to highlight the significance of the negative impact of erroneous EMR data, to provide fundamental principles for managing EMRs, and to provide recommendations to help facilitate the successful use of electronic health data, whether to inform clinical decisions or for clinical research. (C) 2017 International Anesthesia Research Society

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Assessment of Postoperative Analgesic Drug Efficacy: Method of Data Analysis Is Critical.

BACKGROUND: Pain intensity ratings and opioid consumption (OC) are ubiquitous indicators of pain in postoperative trials of the efficacy of interventional procedures. Unfortunately, consensus on the appropriate statistical handling of these outcomes has not been reached. The aim of this article was, therefore, to reexamine original data obtained from a postoperative analgesic drug trial, applying a collection of standard statistical methods in analgesic outcome assessments. Furthermore, a modified integrated assessment method of these outcomes was evaluated. METHODS: Data from a randomized, double-blind, placebo-controlled study investigating the analgesic efficacy of a regional anesthetic block following a major elective surgical procedure were analyzed. The original data included measurements of pain intensity (visual analog scale [VAS]) at rest and during coughing (VAS0/2/4/6/12/18/24 hrs) and OC0-6/0-24 hrs administered by patient-controlled analgesia. The statistical analyses included comparisons of discrete pain intensity scores (VAS0/2/4/6/12/18/24 hrs), summary measures of pain intensity ratings (area under the curve [AUC]-VAS0-6/0-24 hrs; mean VAS0-6/0-24 hrs), and OC0-6/0-24 hrs. Finally, the analyses also included an integrated assessment of longitudinally measured pain intensity and opioid consumption (PIOC0-6/0-24 hrs). Also, estimation of effect size, generalized odds ratio of the individual analgesic outcome variables was performed. RESULTS: Sixty-one patients were included in the final data analysis. Discrete pain intensity ratings differed significantly between the treatment groups at specific postoperative time points, but appropriate correction for multiple comparisons eliminated some of these differences. AUC-VAS0-6 hrs differed significantly at rest and during coughing, while no difference was found for AUC-VAS0-24 hrs. In contrast, mean VAS0-6 hrs and VAS0-24 hrs differed significantly between treatment groups at rest and during coughing. OC0-6/0-24 hrs differed significantly between the treatment groups. Finally, also PIOC0-6/0-24 hrs differed significantly at rest and during coughing. CONCLUSIONS: Our analyses demonstrate that the applied statistical method may alter the statistical significance and estimates of effect size of analgesic outcome variables in postoperative pain trials. Our findings underline the importance of defining valid statistical methods for future analgesic drug trials. We propose an integrated assessment of longitudinally measured pain intensity and opioid consumption (PIOC). The method combines two interdependent analgesic outcomes, lowers the risk of mass significance, and provides more accurate representation of the dynamic nature of postoperative pain and analgesic drug efficacy. (C) 2017 International Anesthesia Research Society

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Hospital-Based Acute Care Within 7 Days of Discharge After Outpatient Arthroscopic Shoulder Surgery.

BACKGROUND: The rate of hospital-based acute care (defined as hospital transfer at discharge, emergency department [ED] visit, or subsequent inpatient hospital [IP] admission) after outpatient procedure is gaining momentum as a quality metric for ambulatory surgery. However, the incidence and reasons for hospital-based acute care after arthroscopic shoulder surgery are poorly understood. METHODS: We studied adult patients who underwent outpatient arthroscopic shoulder procedures in New York State between 2011 and 2013 using the Healthcare Cost and Utilization Project database. ER visits and IP admissions within 7 days of surgery were identified by cross-matching 2 independent Healthcare Cost and Utilization Project databases. RESULTS: The final cohort included 103,476 subjects. We identified 1867 (1.80%, 95% confidence interval [CI], 1.72%-1.89%) events, and the majority of these encounters were ER visits (1643, or 1.59%, 95% CI, 1.51%-1.66%). Direct IP admission after discharged was uncommon (224, or 0.22%, 95% CI, 0.19%-0.24%). The most common reasons for seeking acute care were musculoskeletal pain (23.78% of all events). Nearly half of all events (43.49%) occurred on the day of surgery or on postoperative day 1. Operative time exceeding 2 hours was associated with higher odds of requiring acute care (odds ratio [OR], 1.28; 99% CI, 1.08-1.51). High-volume surgical centers (OR, 0.67; 99% CI, 0.58-0.78) and regional anesthesia (OR, 0.72; 99% CI, 0.56-0.92) were associated with lower odds of requiring acute care. CONCLUSIONS: The rate of hospital-based acute care after outpatient shoulder arthroscopy was low (1.80%). Complications driving acute care visits often occurred within 1 day of surgery. Many of the events were likely related to surgery and anesthesia (eg, inadequate analgesia), suggesting that anesthesiologists may play a central role in preventing acute care visits after surgery. (C) 2017 International Anesthesia Research Society

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Creation and Execution of a Novel Anesthesia Perioperative Care Service at a Veterans Affairs Hospital.

Physician-led perioperative surgical home models are developing as a method for improving the American health care system. These models are novel, team-based approaches that help to provide continuity of care throughout the perioperative period. Another avenue for improving care for surgical patients is the use of enhanced recovery after surgery pathways. These are well-described methods that have shown to improve perioperative outcomes. An established perioperative surgical home model can help implementation, efficiency, and adherence to enhanced recovery after surgery pathways. For these reasons, the Tennessee Valley Healthcare System, Nashville Veterans Affairs Medical Center created an Anesthesiology Perioperative Care Service that provides comprehensive care to surgical patients from their preoperative period through the continuum of their hospital course and postdischarge follow-up. In this brief report, we describe the development, implementation, and preliminary outcomes of the service. (C) 2017 International Anesthesia Research Society

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Stroke Volume Variation-Guided Versus Central Venous Pressure-Guided Low Central Venous Pressure With Milrinone During Living Donor Hepatectomy: A Randomized Double-Blinded Clinical Trial.

BACKGROUND: We previously demonstrated the usefulness of milrinone for living donor hepatectomy. However, a less-invasive alternative to central venous catheterization and perioperative contributors to good surgical outcomes remain undetermined. The current study evaluated whether the stroke volume variation (SVV)-guided method can substitute central venous catheterization during milrinone-induced profound vasodilation. METHODS: We randomly assigned 42 living liver donors to receive either SVV guidance or central venous pressure (CVP) guidance to obtain milrinone-induced low CVP. Target SVV of 9% was used as a substitute for CVP of 5 mm Hg. The surgical field grade evaluated by 2 attending surgeons on a 4-point scale was compared between the CVP- and SVV-guided groups (n = 19, total number of scores = 38 per group) as a primary outcome variable. Multivariable analysis was performed to identify independent factors associated with the best surgical field as a post hoc analysis. RESULTS: Surgical field grades, which were either 1 or 2, were not found to be different between the 2 groups via Mann-Whitney U test (P = .358). There was a very weak correlation between SVV and CVP during profound vasodilation such as CVP

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Improving Outcomes in Emergency General Surgery Patients: What Evidence Is Out There?.

No abstract available

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Mechanical damage to green and red lentil seeds

Abstract

In this research, the breakage susceptibility of two classes of lentil (green and red) was evaluated as affected by impact energy and seed moisture content. The experiments were conducted at impact energies of 0.1, 0.2 and 0.3 J, and moisture contents of 10, 12.5, 15, 17.5, 20 and 25% (wet basis). Results showed that red lentil seeds had more breakage than green seeds and the difference in breakage percentage between green and red lentil seeds was significant at 0.01% level according to analysis of variance (p < .01). Percentage breakage of both green and red lentil seeds increased as the energy of impact increased. With increasing the seed moisture content of the both green and red lentils, the breakage percentage of seeds decreased. The average values of seeds breakage green and red lentil seeds varied from 100 to 67.7% and from 100 to 93.1%, respectively, as the seeds moisture content increased from 10 to 25%. The optimum seed moisture at which minimum damage was observed was 17.5% for green lentil and 15% for red lentil. Mathematical relationships composed of lentil seeds moisture content and energy of impact were developed for accurate description of the breakage percentage of green and red lentil seeds under impact loading.

The objective of this research was to determine the effects of moisture content and impact energy on the breakage susceptibility of two classes of lentil (green and red). The experiments were conducted at moisture contents of 10, 12.5, 15, 17.5, 20 and 25% on a- wet basis (w.b.), and at impact energies of 0.1, 0.2 and 0.3 J. Breakage percentage of both green and red lentil seeds increased as the impact energy increased. Red lentil seeds had more breakage than green seeds and the difference in breakage percentage between green and red lentil seeds was significant at 0.01% level according to analysis of variance (p < .01).

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Determination of the protein quality of cooked Canadian pulses

Abstract

A study to determine the protein digestibility-corrected amino acid score and protein efficiency ratio of nine different cooked Canadian pulse classes was conducted in support of the establishment of protein quality claims in Canada and the United States. Split green and yellow pea, whole green lentil, split red lentil, Kabuli chickpea, navy bean, pinto bean, light red kidney bean, and black bean were investigated. Protein digestibility-corrected amino acid score (PDCAAS) and the protein efficiency ratio (PER) were determined using the appropriate rodent models. All pulses had high digestibility values, >70%, with PDCAAS values greater than 0.5, thereby qualifying as a quality protein in the United States, but only navy beans qualified as a good source of protein. All pulses except whole green lentils, split red lentils, and split green peas would qualify as sources of protein with protein ratings between 20 and 30.4 in Canada. These findings support the use of pulses as protein sources in the regulatory context of both the United States and Canada.

Pulses are consumed globally and are high in protein, but have to be cooked prior to consumption. This article describes the effect of cooking on the protein digestibility and amino acid composition of 9 pulse classes.

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Nutritional quality of Oyster Mushroom (Pleurotus Ostreatus) as affected by osmotic pretreatments and drying methods

Abstract

This study was conducted to evaluate the effects of different levels of osmotic pretreatments prior to drying and different drying methods on nutritional quality of dried mushroom slices. The experiment consisted of sun, solar, and oven drying after dipping the slices in salt solutions of 5 and 10% concentrations for 50 minutes, the control being untreated mushroom sample. Significant differences in proximate composition were observed between the fresh and dried mushroom samples. The average mean value of crude protein, crude fat, crude fiber, ash, and carbohydrates of the fresh mushroom samples were 28.85, 2.47, 12.87, 9.76 and 48.16% as compared to 25.91, 2.18, 10.41, 10.91 and 42.14% for dried samples. Oven drying resulted in higher content of ash (11.06%) and carbohydrates (43.64%) and lower contents of crude protein (24.99%), crude fat (2.12%), and crude fiber (10.21%). The osmotic pretreatments significantly affected the composition of the dried mushroom samples. As salt concentration increased from 0 to 5 and 10%, the protein content reduced from 26.78 to 25.99 and 24. 95%, the fat reduced from 2.42 to 2.19 and 1.94, and fiber from 12.82 to 9.41 and 9.01%, respectively. Contrarily, the ash increased from 9.75 to 12.20%, and the carbohydrate from 38.16 to 43.08 and 45.18%, respectively.

Preservation of mushroom through drying and popularizing in the community is helpful for its health benefit and high protein content. Mushroom growers, suppliers, and consumers can be benefited from mushroom business as the shelf life of this produce is extended for longer period of time.

http://ift.tt/2trwCGO

Ultraviolet light-C increases antioxidant capacity of the strawberry (Fragaria x ananassa) in vitro and in high-fat diet-induced obese rats

Abstract

Flavonoids and polyphenols from the strawberry and other fruits have been proposed to reduce the oxidative stress produced by the obesity and her complications. Moreover, it has been proposed that irradiation with UV-C to strawberry may increase the antioxidant capacity of this fruit. The aim of the present study was to explore the effects of the UV-C on antioxidant capacity of strawberry in vitro and in vivo. Strawberry slices were irradiated with ultraviolet light-C (UV-C) at 1.2 W/m²/16.5 min; then, the power antioxidant was isolated from the nonirradiated and irradiated strawberry slices into an organic phase, which was lyophilized to finally producing a nonirradiated strawberry extract (NSE) and UV-irradiated strawberry extract (UViSE) powder. After the antioxidant capacity of both extracts were determined in vitro using the Trolox equivalent antioxidant capacity (TEAC) assay and in vivo using high-fat diet-induced obese rats. Our results demonstrated that irradiation with UV-C to strawberry slices increased the antioxidants content, which was corroborated in vitro, where the antioxidant capacity of UViSE was higher than the NSE. However, in obese rats, the reduction in the oxidative damage by the UViSE and NSE were similar in peripheral tissues. Interestingly, the UViSE was better than the NSE to reduce the oxidative damage in brain. In conclusion, UV-irradiation increases the antioxidants content of strawberry that is correlated with an increased antioxidant capacity in vitro, but in rats, this antioxidant capacity may be more effective in brain than in peripheral tissues.

UV-irradiation increases the antioxidants content of strawberry that is correlated with an increased antioxidant capacity in vitro, but in rats, this antioxidant capacity may be more effective in brain than in peripheral tissues.

http://ift.tt/2trIwk6

Chiral Responsive Liquid Quantum Dots

How to convert the weak chiral-interaction into the macroscopic properties of materials remains a huge challenge. Here, this study develops highly fluorescent, selectively chiral-responsive liquid quantum dots (liquid QDs) based on the hydrophobic interaction between the chiral chains and the oleic acid-stabilized QDs, which have been designated as (S)-1810-QDs. The fluorescence spectrum and liquidity of thermal control demonstrate the fluorescence properties and the fluidic behavior of (S)-1810-QDs in the solvent-free state. Especially, (S)-1810-QDs exhibit a highly chiral-selective response toward (1R, 2S)-2-amino-1,2-diphenyl ethanol. It is anticipated that this study will facilitate the construction of smart chiral fluidic sensors. More importantly, (S)-1810-QDs can become an attractive material for chiral separation.

Highly fluorescent, selectively chiral-responsive liquid quantum dots (QDs) are developed, which exhibit a chiral-selective response toward (1R, 2S)-2-amino-1,2-diphenyl ethanol. It is anticipated that this study will facilitate the construction of smart chiral fluidic sensors. More importantly, the liquid QDs can become an attractive material for chiral separation.

http://ift.tt/2sS27gq

Cross-sectional association between ZIP code-level gentrification and homelessness among a large community-based sample of people who inject drugs in 19 US cities

Background

Housing instability has been associated with poor health outcomes among people who inject drugs (PWID). This study investigates the associations of local-level housing and economic conditions with homelessness among a large sample of PWID, which is an underexplored topic to date.

Methods

PWID in this cross-sectional study were recruited from 19 large cities in the USA as part of National HIV Behavioral Surveillance. PWID provided self-reported information on demographics, behaviours and life events. Homelessness was defined as residing on the street, in a shelter, in a single room occupancy hotel, or in a car or temporarily residing with friends or relatives any time in the past year. Data on county-level rental housing unaffordability and demand for assisted housing units, and ZIP code-level gentrification (eg, index of percent increases in non-Hispanic white residents, household income, gross rent from 1990 to 2009) and economic deprivation were collected from the US Census Bureau and Department of Housing and Urban Development. Multilevel models evaluated the associations of local economic and housing characteristics with homelessness.

Results

Sixty percent (5394/8992) of the participants reported homelessness in the past year. The multivariable model demonstrated that PWID living in ZIP codes with higher levels of gentrification had higher odds of homelessness in the past year (gentrification: adjusted OR=1.11, 95% CI=1.04 to 1.17).

Conclusions

Additional research is needed to determine the mechanisms through which gentrification increases homelessness among PWID to develop appropriate community-level interventions.

http://ift.tt/2rPwkMW

Still Autonomous After All

Abstract

Recent mechanistic philosophers (in particular, Boone and Piccinini in Synthese 193(5):1287–1321, 2016) have argued that the cognitive sciences are not autonomous from neuroscience proper. I clarify two senses of autonomy–metaphysical and epistemic—and argue that cognitive science is still autonomous in both senses. Moreover, mechanistic explanation of cognitive phenomena is not therefore an alternative to the view that cognitive science is autonomous of neuroscience. If anything, it's a way of characterizing just how cognitive processes are implemented by neural mechanisms.

http://ift.tt/2sS2uHQ

Selective Growth of Metal-Free Metallic and Semiconducting Single-Wall Carbon Nanotubes

A major obstacle for the use of single-wall carbon nanotubes (SWCNTs) in electronic devices is their mixture of different types of electrical conductivity that strongly depends on their helical structure. The existence of metal impurities as a residue of a metallic growth catalyst may also lower the performance of SWCNT-based devices. Here, it is shown that by using silicon oxide (SiO_x) nanoparticles as a catalyst, metal-free semiconducting and metallic SWCNTs can be selectively synthesized by the chemical vapor deposition of ethanol. It is found that control over the nanoparticle size and the content of oxygen in the SiO_x catalyst plays a key role in the selective growth of SWCNTs. Furthermore, by using the as-grown semiconducting and metallic SWCNTs as the channel material and source/drain electrodes, respectively, all-SWCNT thin-film transistors are fabricated to demonstrate the remarkable potential of these SWCNTs for electronic devices.

Semiconducting and metallic single-wall carbon nanotubes (SWCNTs) are controllably synthesized using silicon oxide nanoparticles with tuned oxygen deficiencies as a catalyst. Totally metal-free, all-SWCNT thin-film transistors are fabricated using the as-grown semiconducting and metallic SWCNTs as channel and source/drain electrodes, respectively, which demonstrates desirable overall performance.

http://ift.tt/2rBp4QC

Controlling the Photonic Properties of Cholesteric Cellulose Nanocrystal Films with Magnets

The self-assembly of cellulose nanocrystals is a powerful method for the fabrication of biosourced photonic films with a chiral optical response. While various techniques have been exploited to tune the optical properties of such systems, the presence of external fields has yet to be reported to significantly modify their optical properties. In this work, by using small commercial magnets (≈ 0.5–1.2 T) the orientation of the cholesteric domains is enabled to tune in suspension as they assemble into films. A detailed analysis of these films shows an unprecedented control of their angular response. This simple and yet powerful technique unlocks new possibilities in designing the visual appearance of such iridescent films, ranging from metallic to pixelated or matt textures, paving the way for the development of truly sustainable photonic pigments in coatings, cosmetics, and security labeling.

Commercial magnets can be used to control the optical properties of cholesteric cellulose nanocrystals films, resulting in photonic structures with an unprecedented photonic response. This striking effect unlocks new possibilities in the already broad range of photonic applications of such systems; from colorants, to sensors and security devices.

http://ift.tt/2szlub5

Flash Light Millisecond Self-Assembly of High χ Block Copolymers for Wafer-Scale Sub-10 nm Nanopatterning

One of the fundamental challenges encountered in successful incorporation of directed self-assembly in sub-10 nm scale practical nanolithography is the process compatibility of block copolymers with a high Flory–Huggins interaction parameter (χ). Herein, reliable, fab-compatible, and ultrafast directed self-assembly of high-χ block copolymers is achieved with intense flash light. The instantaneous heating/quenching process over an extremely high temperature (over 600 °C) by flash light irradiation enables large grain growth of sub-10 nm scale self-assembled nanopatterns without thermal degradation or dewetting in a millisecond time scale. A rapid self-assembly mechanism for a highly ordered morphology is identified based on the kinetics and thermodynamics of the block copolymers with strong segregation. Furthermore, this novel self-assembly mechanism is combined with graphoepitaxy to demonstrate the feasibility of ultrafast directed self-assembly of sub-10 nm nanopatterns over a large area. A chemically modified graphene film is used as a flexible and conformal light-absorbing layer. Subsequently, transparent and mechanically flexible nanolithography with a millisecond photothermal process is achieved leading the way for roll-to-roll processability.

Wafer-scale millisecond level directed self-assembly of high-χ block copolymers (BCPs) are successfully demonstrated by photothermal effect of achromatic flash light. Milliseconds-duration extremely high-temperature (≈600 °C) process near the order–disorder transition temperature (T_ODT) of high-χ BCPs enables extraordinary grain growth without noticeable thermal degradation even in atmospheric conditions.

http://ift.tt/2rPwALU

Amino-Functionalized ZIF-7 Nanocrystals: Improved Intrinsic Separation Ability and Interfacial Compatibility in Mixed-Matrix Membranes for CO2/CH4 Separation

Highly permeable and selective, as well as plasticization-resistant membranes are desired as promising alternatives for cost- and energy-effective CO₂ separation. Here, robust mixed-matrix membranes based on an amino-functionalized zeolitic imidazolate framework ZIF-7 (ZIF-7-NH₂) and crosslinked poly(ethylene oxide) rubbery polymer are successfully fabricated with filler loadings up to 36 wt%. The ZIF-7-NH₂ materials synthesized from in situ substitution of 2-aminobenzimidazole into the ZIF-7 structure exhibit enlarged aperture size compared with monoligand ZIF-7. The intrinsic separation ability for CO₂/CH₄ on ZIF-7-NH₂ is remarkably enhanced as a result of improved CO₂ uptake capacity and diffusion selectivity. The incorporation of ZIF-7-NH₂ fillers simultaneously makes the neat polymer more permeable and more selective, surpassing the state-of-the-art 2008 Robeson upper bound. The chelating effect between metal (zinc) nodes of fillers and ester groups of a polymer provides good bonding, enhancing the mechanical strength and plasticization resistance of the neat polymer membrane. The developed novel ZIF-7 structure with amino-function and the resulting nanocomposite membranes are very attractive for applications like natural-gas sweetening or biogas purification.

Amino-functionalized zeolitic imidazolate framework-7 (ZIF-7-NH₂) nanocrystals fabricated from a mixed-linker strategy exhibit enlarged aperture size and enhanced CO₂ uptake capacity compared to the original ZIF-7 structure. Incorporation of these fillers into a poly(ethylene oxide)-based rubbery polymer membrane can significantly improve the gas permeability, selectivity, and plasticization-resistant properties. The developed novel ZIF structure and the resulting hybrid membranes are very attractive for natural-gas sweetening or biogas purification.

http://ift.tt/2szklQv

Growth of Au Nanoparticles on 2D Metalloporphyrinic Metal-Organic Framework Nanosheets Used as Biomimetic Catalysts for Cascade Reactions

Inspired by the multiple functions of natural multienzyme systems, a new kind of hybrid nanosheet is designed and synthesized, i.e., ultrasmall Au nanoparticles (NPs) grown on 2D metalloporphyrinic metal-organic framework (MOF) nanosheets. Since 2D metalloporphyrinic MOF nanosheets can act as the peroxidase mimics and Au NPs can serve as artificial glucose oxidase, the hybrid nanosheets are used to mimic the natural enzymes and catalyze the cascade reactions. Furthermore, the synthesized hybrid nanosheets are used to detect biomolecules, such as glucose. This study paves a new avenue to design nanomaterial-based biomimetic catalysts with multiple complex functions.

Inspired by the multiple functions of natural multienzyme systems, hybrid nanosheets are designed and synthesized, i.e., ultrasmall Au nanoparticles are grown on 2D metalloporphyrinic metal-organic framework nanosheets. Since nanosheets can act as the peroxidase mimics and Au nanoparticles can serve as artificial glucose oxidase, the hybrid nanosheets are used to mimic the natural enzymes and catalyze the cascade reactions.

http://ift.tt/2rPnSgr

Chemical Vapor Deposition of Bernal-Stacked Graphene on a Cu Surface by Breaking the Carbon Solubility Symmetry in Cu Foils

The synthesis of Bernal-stacked multilayer graphene over large areas is intensively investigated due to the value of this material's tunable electronic structure, which makes it promising for use in a wide range of optoelectronic applications. Multilayer graphene is typically formed via chemical vapor deposition onto a metal catalyst, such as Ni, a Cu–Ni alloy, or a Cu pocket. These methods, however, require sophisticated control over the process parameters, which limits the process reproducibility and reliability. Here, a new synthetic method for the facile growth of large-area Bernal-stacked multilayer graphene with precise layer control is proposed. A thin Ni film is deposited onto the back side of a Cu foil to induce controlled diffusion of carbon atoms through bulk Cu from the back to the front. The resulting multilayer graphene exhibits a 97% uniformity and a sheet resistance of 50 Ω sq⁻¹ with a 90% transmittance after doping. The growth mechanism is elucidated and a generalized kinetic model is developed to describe Bernal-stacked multilayer graphene growth by the carbon atoms diffused through bulk Cu.

A synthetic approach for Bernal-stacked multilayer graphene on Cu foil via chemical vapor deposition is proposed. Uniform Bernal-stacked graphene is synthesized on a large-area by depositing carbon reservoir on the backside of Cu foil. The resulting graphene exhibits a tunable bandgap under vertical electric fields.

http://ift.tt/2sz491R

Bis-Tridentate Ir(III) Metal Phosphors for Efficient Deep-Blue Organic Light-Emitting Diodes

Emissive Ir(III) metal complexes possessing two tridentate chelates (bis-tridentate) are known to be more robust compared to those with three bidentate chelates (tris-bidentate). Here, the deep-blue-emitting, bis-tridentate Ir(III) metal phosphors bearing both the dicarbene pincer ancillary such as 2,6-diimidazolylidene benzene and the 6-pyrazolyl-2-phenoxylpyridine chromophoric chelate are synthesized. A deep-blue organic light-emitting diode from one phosphor exhibits Commission Internationale de l'Eclairage (CIE_(x,y)) coordinates of (0.15, 0.17) with maximum external quantum efficiency (max. EQE) of 20.7% and EQE = 14.6% at the practical brightness of 100 cd m⁻².

A deep-blue organic light-emitting diode (OLED) from one bis-tridentate Ir(III) phosphor 5 exhibits CIE(x,y) coordinates of (0.15, 0.17) with maximum external quantum efficiency (max. EQE) of 20.7% and EQE = 14.6% at the practical brightness of 100 cd m⁻².

http://ift.tt/2tMAnpw

Antipulverization Electrode Based on Low-Carbon Triple-Shelled Superstructures for Lithium-Ion Batteries

The realization of antipulverization electrode structures, especially using low-carbon-content anode materials, is crucial for developing high-energy and long-life lithium-ion batteries (LIBs); however, this technology remains challenging. This study shows that SnO₂ triple-shelled hollow superstructures (TSHSs) with a low carbon content (4.83%) constructed by layer-by-layer assembly of various nanostructure units can withstand a huge volume expansion of ≈231.8% and deliver a high reversible capacity of 1099 mAh g⁻¹ even after 1450 cycles. These values represent the best comprehensive performance in SnO₂-based anodes to date. Mechanics simulations and in situ transmission electron microscopy suggest that the TSHSs enable a self-synergistic structure-preservation behavior upon lithiation/delithiation, protecting the superstructures from collapse and guaranteeing the electrode structural integrity during long-term cycling. Specifically, the outer shells during lithiation processes are fully lithiated, preventing the overlithiation and the collapse of the inner shells; in turn, in delithiation processes, the underlithiated inner shells work as robust cores to support the huge volume contraction of the outer shells; meanwhile, the middle shells with abundant pores offer sufficient space to accommodate the volume change from the outer shell during both lithiation and delithiation. This study opens a new avenue in the development of high-performance LIBs for practical energy applications.

SnO₂ triple-shelled hollow superstructures with a low carbon content (4.83%) can withstand a huge volume expansion of ≈231.8% and deliver a high reversible capacity of 1099 mAh g⁻¹ even after 1450 cycles, due to their self-synergistic structure-preservation behavior that protects the superstructures from collapse and guarantees the electrode structural integrity during long-term cycling.

http://ift.tt/2sOy600

Early Palliative Care for Patients with Hematologic Malignancies: Is It Really so Difficult to Achieve?

Abstract

Evidence points to many benefits of "early palliative care," the provision of specialist palliative care services upstream from the end of life, to improve patients' quality of life while living with a serious illness. Yet most trials of early palliative care have not included patients with hematologic malignancies. Unfortunately, patients with hematologic malignancies are also known to have substantial illness burden, poor quality of life, and aggressive care at the end of life, including a greater likelihood of dying in the hospital, receiving chemotherapy at the end of life, and low hospice utilization, compared to patients with solid tumors. Given these unmet needs, one must wonder, why is palliative care so underutilized in this population? In this article, we discuss barriers to palliative care integration in hematology, highlight several reports of successful integration, and suggest specific indications for involving palliative care in the management of hematologic malignancy patients.

http://ift.tt/2trz3cA

Enucleation of solid pseudopapillary tumor with a preoperative nasopancreatic drainage stent in a child

Abstract

Solid pseudopapillary tumor (SPT) is a rare pancreatic tumor with low-grade malignancy in children. A complete surgical resection can achieve a favorable prognosis. Although several reports have indicated that enucleation is considered a safe and effective treatment, the most significant complication is injury to the main pancreatic duct. The usefulness and safety of tumor enucleation after preoperative placement of an endoscopic nasopancreatic drainage stent (NPDS) has recently been reported. We present the case of SPT in a 10-year-old girl. To avoid and detect injury to the main pancreatic duct during operation, an NPDS was endoscopically placed before laparotomy. The patient underwent a complete enucleation of the tumor with the guidance of an NPDS. Our case is the first report of a successful enucleation of an SPT with a preoperative placement of an NPDS. This procedure may lead to safe enucleation of a pancreatic tumor with low malignancy, such as SPT, in children.

http://ift.tt/2sz3hdB

Laparoscopic surgery for sigmoid colon cancer after multiple operations including urinary diversion with Indiana pouch: A case report

Abstract

A 73-year-old man with lower abdominal pain was diagnosed at our hospital with sigmoid colon cancer. He had previously undergone radical cystectomy with Indiana pouch construction and gastrectomy to treat bladder cancer and gastric cancer, respectively. We performed a laparoscopic Hartmann's operation with Japanese D3 lymph node dissection. We observed severe adhesion in the abdominal cavity; adhesions between the urostomy and sigmoid colon were particularly severe. The tumor had invaded to the distal rectum, which had adhered to the pubic bone and the previously reconstructed urinary pouch. By performing careful and persistent laparoscopic dissection, we completed the operation without damaging the urostomy and with no remnant tumor tissue (R0). The postoperative course was uneventful, and the patient was doing well with no evidence of cancer recurrence 1 year after surgery.

http://ift.tt/2rPtCXA

Rational Design of Na(Li1/3Mn2/3)O2 Operated by Anionic Redox Reactions for Advanced Sodium-Ion Batteries

In an effort to develop high-energy-density cathodes for sodium-ion batteries (SIBs), low-cost, high capacity Na(Li_1/3Mn_2/3)O₂ is discovered, which utilizes the labile O 2p-electron for charge compensation during the intercalation process, inspired by Li₂MnO₃ redox reactions. Na(Li_1/3Mn_2/3)O₂ is systematically designed by first-principles calculations considering the Li/Na mixing enthalpy based on the site preference of Na in the Li sites of Li₂MnO₃. Using the anionic redox reaction (O²⁻/O⁻), this Mn-oxide is predicted to show high redox potentials (≈4.2 V vs Na/Na⁺) with high charge capacity (190 mAh g⁻¹). Predicted cathode performance is validated by experimental synthesis, characterization, and cyclic performance studies. Through a fundamental understanding of the redox reaction mechanism in Li₂MnO₃, Na(Li_1/3Mn_2/3)O₂ is designed as an example of a new class of promising cathode materials, Na(Li_1/3M_2/3)O₂ (M: transition metals featuring stabilized M⁴⁺), for further advances in SIBs.

Inspired by Li₂MnO₃ redox reactions, Na(Li_1/3Mn_2/3)O₂ operated by anionic redox reactions (labile lone-pair O) is rationally designed based on the site preference of Na in the Li sites of Li₂MnO₃ for high-energy-density cathodes. Na(Li_1/3Mn_2/3)O₂ shows high redox potentials (≈4.2 V vs Na/Na⁺) with high charge capacity (190 mAh g⁻¹), utilizing O²⁻/O⁻ anionic redox with the fixed Mn⁴⁺ during desodiation.

http://ift.tt/2rTIX4P

Highly Stretchable, Shape Memory Organohydrogels Using Phase-Transition Microinclusions

Shape memory effect in polymer materials has attracted considerable attention due to its promising applications in a variety of fields. However, shape memory polymers prepared by conventional strategy suffer from a common problem, in which high strain capacity and excellent shape memory behavior cannot be simultaneously achieved. This study reports a general and synergistic strategy to fabricate high-strain and tough shape memory organohydrogels that feature binary cooperative phase. The phase- transition micro-organogels and elastic hydrogel framework act synergistically to provide excellent thermomechanical performance and shape memory effect. During shape memory process, the organohydrogels exhibit high strain capacity, featuring fully recoverable stretching deformation by up to 2600% and compression by up to 85% beneath a load ≈20 times the organohydrogel's weight. Furthermore, owing to the micro-organogel and hydrogel heterostructures, the interfacial tension derived from heterophases dominates the shape recovery of the organohydrogel material. Simple processing and smart surface patterning of the shape memory behavior and multiple shape memory effects can also be realized. Meanwhile, these organohydrogels are also nonswellable in water and oil, which is important for multimedia applications.

Highly stretchable, shape memory organohydrogels that feature binary cooperative phase are fabricated by utilizing a synergistic strategy. The phase-transition micro-organogels and elastic hydrogel framework act synergistically to provide excellent thermomechanical performance and shape memory effect. During shape memory process, the organohydrogels exhibit simple processing, smart surface patterning, and multiple shape memory effects. Meanwhile, nonswellable capacity can be realized.

http://ift.tt/2sp1Vni

Pharmacological intervention of MKL/SRF signaling by CCG-1423 impedes endothelial cell migration and angiogenesis

Abstract

De novo synthesis of cytoskeleton-regulatory proteins triggered by the megakaryoblastic leukemia (MKL)/serum response factor (SRF) transcriptional system in response to pro-angiogenic growth factors lies at the heart of endothelial cell (EC) migration (a critical element of angiogenesis) and neovascularization. This study explores whether pharmacological intervention of MKL/SRF signaling axis by CCG-1423 is able to suppress angiogenesis. Our studies show that CCG-1423 inhibits migration and cord morphogenesis of EC in vitro and sprouting angiogenesis ex vivo and in vivo, suggesting CCG-1423 could be a novel anti-angiogenic agent. Kymography analyses of membrane dynamics of EC revealed that CCG-1423 treatment causes a major defect in membrane protrusion. CCG-1423 treatment led to attenuated expression of several actin-binding proteins that are important for driving membrane protrusion including ArpC2, VASP, and profilin1 (Pfn1) with the most drastic effect seen on the expression of Pfn1. Finally, depletion of Pfn1 alone is also sufficient for a dramatic decrease in sprouting angiogenesis of EC in vitro and ex vivo, further suggesting that Pfn1 depletion may be one of the mechanisms of the anti-angiogenic action of CCG-1423.

http://ift.tt/2sRCmN3

Multiple Sclerosis in Latin Americans: Genetic Aspects

Abstract

Latin Americans (LA) are a heterogeneous, multiethnic group of individuals who inhabit the continental countries in Latin America (LATAM), Caribbean islands and constitute the largest ethnic minority in the USA. Commonly used terminology and ethno racial classifications to define these groups may not be accurate. Risk for multiple sclerosis (MS) among LA is generally low to medium but frequencies are increasing in the American hemisphere. Genome-Wide Association Studies (GWAS) in LA show diverse variants and genetic proportions among Mestizos, the most representative ethnic population, who themselves are the product of centuries of interracial mixing between Native Americans (or Amerindians), White Caucasian Europeans, and Black Africans. Genetic distribution diversity appears to be related to migratory and historical and socio-political factors in LATAM. Epidemiologic studies show an extremely low prevalence of MS among non-mixed Amerindians; this has been attributed to protective ancestral Asian genetics and possibly, environmental factors. Mestizos and biracial LA of African ancestry have more susceptibility to MS apparently due to the historical introduction of the European HLA-DRB1*1501 gene. Contribution from HLA typing, GWAS, and ancestry informative markers (AIMs) has been determinant in the current LA genetic understanding but more regional studies are needed. The relationship between genetics and disease regional distribution is emphasized.

http://ift.tt/2sUvv59

Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions (SONAR)

Abstract

A 43-year-old female with multiple sclerosis developed urethral melanoma. The only potential risk factor was treatment with natalizumab, a humanized monoclonal antibody against α4 integrins. To investigate the risk-exposure relationship, we reviewed this case, all other published cases, and cases of natalizumab-associated melanoma reported to regulatory agencies. Data sources included the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) (2004–2014), a FDA Advisory Committee Meeting Report, and peer-reviewed publications. In the United States, the manufacturer maintains an FDA-mandated Tysabri Safety Surveillance Program (part of the Tysabri Outcomes Unified Commitment to Health (TOUCH)) of natalizumab-treated patients. We statistically compared reporting completeness for natalizumab-associated melanoma cases in FAERs for which information was obtained entirely from the TOUCH program versus cases where FAERS information was supplemented by TOUCH program information. FAERS included 137 natalizumab-associated melanoma reports in patients with multiple sclerosis. Median age at melanoma diagnosis was 45 years (range: 21–74 years). Changes in preexisting nevi occurred in 16%, history of cutaneous nevi occurred in 22%, diagnosis within 2 years of beginning natalizumab occurred in 34%, and 74% had primary surgical treatment. Among seven natalizumab-treated MS patients who developed biopsy-confirmed melanoma on treatment and reported in the literature, median age at diagnosis was 41 years (range: 38–48 years); and the melanoma diagnosis occurred following a median of 12 natalizumab doses (range: 1–77 doses). A history of mole or nevi was noted in four patients and a history of prior melanoma was noted in one patient. Completeness scores for reports were significantly lower for FAERS cases reported from the TOUCH program versus FAERS cases supplemented by TOUCH information (median score of 2 vs. 4 items out of 8-possible items, P < 0.0007). Clinicians should monitor existing nevi and maintain suspicion for melanoma developing in natalizumab-treated patients. The TOUCH Safety Surveillance Program, currently focused on progressive multifocal leukoencephalopathy, should be expanded to include information on other serious complications including malignancies, particularly if they are immunologic in nature.

This article identifies a case of urethral melanoma developing shortly after initiating natalizumab therapy for multiple sclerosis. Literature review identifies seven cases of natalizumab-associated melanoma and FDA review identifies 133 cases of natalizumab-associated melanoma. Patients initiating natalizumab therapy may consider having a baseline dermatologic evaluation, particularly if cutaneous nevi are present.

http://ift.tt/2rToqNI

Prevalence of and risk factors for severe cognitive and sleep symptoms in ME/CFS and MS

There are considerable phenotypic and neuroimmune overlaps between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and multiple sclerosis (MS). While the precise aetiologies of both MS and ME/CFS a...

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Achalasia leading to diagnosis of adenocarcinoma of the oesophagus

A 50-year-old male with a 7 month history of progressive dysphagia to solids then subsequently to liquids. He underwent a diagnostic gastroscopy which was normal. A further barium swallow suggested achalasia. He was referred to a tertiary centre, where he underwent pH and manometry studies which confirmed a diagnosis of achalasia. He was referred for a laparoscopic cardiomyotomy, and at surgery there was a suspected tumour at the gastro-oesophageal junction. A follow-up endoscopy with biopsies was normal. Following this, a positron emission tomography scan showed T3 distal oesophageal cancer with no nodal involvement or distal metastasis. An attempt at oesophagectomy was performed, but at operation there was locally advanced carcinoma infiltrating the coeliac axis. He is currently undergoing palliative chemotherapy.

http://ift.tt/2rBuFX3

Regular aerobic exercise reduces endothelin-1 mediated vasoconstrictor tone in overweight and obese adults

Abstract

Endothelin (ET)-1-mediated vasoconstrictor tone is elevated in overweight and obese adults, contributing to vasomotor dysfunction and increased cardiovascular disease risk. While the effects of habitual aerobic exercise on endothelium-dependent vasodilation in overweight/obese adults has been studied, little is known regarding ET-1 vasoconstriction. Accordingly, the aims of the present study were to determine: (1) if regular aerobic exercise training reduces ET-1-mediated vasoconstrictor tone in overweight and obese adults; and, if so (2) whether the reduction in ET-1 vasoconstriction contributes to exercise-induced improvement in endothelium-dependent vasodilation in this population. Forearm blood flow (FBF) to intra-arterial infusion of selective ET_A receptor blockade (BQ-123, 100 nmol min⁻¹ for 60 min), acetylcholine (4.0, 8.0 and 16.0 μg/100 ml tissue min⁻¹) in the absence and presence of ET_A receptor blockade and sodium nitroprusside (1.0, 2.0 and 4.0 μg/100 ml tissue min⁻¹) were determined before and after a 3-month aerobic exercise training intervention in 25 (16M/9F) overweight/obese (BMI: 30.1 ± 0.5 kg m⁻²) adults. The vasodilator response to BQ-123 was significantly lower (∼25%) and the FBF responses to acetylcholine were ∼35% higher after exercise training. Before the exercise intervention the co-infusion of acetylcholine+BQ-123 resulted in a greater vasodilator response than acetylcholine alone; however, after the exercise intervention the FBF response to acetylcholine was not significantly increased by ET_A receptor blockade. These results demonstrate that regular aerobic exercise reduces ET-1-mediated vasoconstrictor tone in previously sedentary overweight and obese adults. Moreover, decreased ET-1 vasoconstriction is an important mechanism underlying the aerobic exercise-induced improvement in endothelium-dependent vasodilator function in overweight/obese adults.

This article is protected by copyright. All rights reserved

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Strategic Studying Limits the Costs of Divided Attention

Multitasking while studying may impair overall memory for the study material, but your ability to strategically identify and remember the most important information may stay intact, according to new findings published in Psychological Science, a journal of the Association for Psychological Science.

"Dividing attention wasn't necessarily a good thing for learning and recall, but we found that distracted participants were just as likely to recall the most important information as were participants who were able to give the presented information their full attention," explains psychology researcher Catherine D.  Middlebrooks of the University of California, Los Angeles.  "The ability to prioritize high-value information during study was consistently immune to the effects of divided attention, regardless of the extent of the distractions that participants faced."

Previous research has shown that learners are able to compensate for the limitations of memory by prioritizing certain information and essentially sacrificing other information as they study. That is, they strategically compensate for factors that are beyond their control – but deploying this strategic approach to studying itself requires cognitive resources. Middlebrooks and UCLA co-authors Tyson K. Kerr and Alan D. Castel wanted to know whether learners have sufficient cognitive resources to overcome the potential costs incurred by studying strategically.

In one experiment, the researchers asked 192 undergraduate student participants to view a series of word lists and remember as many words as possible. Importantly, each word had a numerical value, from 1 to 10, and participants were instructed to maximize the total value of the words they recalled.

Students randomly assigned to the divided attention group studied the word lists as digits were also being read aloud – they were instructed to press a key every time they heard three odd digits in a row. Other students studied the lists while lyrical music, with which they were familiar or unfamiliar, played in the background. Another group of students studied with no additional distractions.

As expected, those students who were forced to divide their attention between the word list and the digits recalled fewer words compared with the students in the other groups. The data showed that the background music had no discernible effect on students' overall recall.

Importantly, students really did seem to pay attention to the value of the words – their odds of recalling a 10-point word were almost five times greater than their odds of recalling a 1-point word. The link between value and recall held for students in all of the groups, regardless of whether they studied with or without distraction.

The findings suggest that the students adjusted their studying to compensate for their study conditions, paying particular attention to the most important study items.

A second experiment, in which students had to divide their attention between studying word lists and completing tone-monitoring tasks that varied in difficulty, showed a similar pattern of results. Participants performed worse when their attention was divided, but they were still able to selectively remember the high-value words.

In both experiments, participants were better able to remember the words as they gained more experience with the task, suggesting that their ability to study selectively improved with practice.

"Situations in which we can actually give something our full, truly undivided attention are often few and far between—at any given moment, you're likely to be distracted to some extent by a number of factors," says Middlebrooks. "Our findings don't suggest that multi-tasking or being distracted will never affect how well we might prioritize important information, but they do suggest that distraction does not automatically doom our efforts and that we seem to consider their costs when deciding how best to allocate our limited resources."

 In future research, Middlebrooks and colleagues hope to explore how various real-world factors – such as having to choose which material to study and how—might affect strategic studying.

This work was supported by the National Institutes of Health National Institute on Aging (Award No. R01AG044335 to A. D. Castel).

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Primary tumor sites in relation to ultraviolet radiation exposure and skin visibility correlate with survival in cutaneous melanoma

Abstract

The prognostic value of detailed anatomic site and ultraviolet radiation (UVR) exposure patterns has not been fully determined in cutaneous melanoma. Thus, we reviewed medical records for detailed site in a population-based retrospective Swedish patient cohort diagnosed with primary invasive melanoma 1976 − 2003 (n=5,973). We followed the patients from date of diagnosis until death, emigration or December 31^st 2013, and evaluated melanoma-specific survival by subsite in a multivariable regression model adjusting for established prognostic factors. We found that melanoma on chronic UVR exposure sites (face, dorsum of hands; adjusted HR 0.6; CI 0.4 − 0.7) and moderately intermittent UVR sites (lateral arms, lower legs, dorsum of feet; HR 0.7; CI 0.6 − 0.8) were associated with a favorable prognosis compared with highly intermittent sites (chest, back, neck, shoulders, thighs). Further, melanoma on poorly visible skin sites upon self-examination (scalp, retroauricular area, back, posterior upper arms and thighs, buttocks, pubic area; HR 1.3; CI 1.1 − 1.5) had a worse prognosis than those on easily visible sites (face, chest, abdomen, anterior upper arms and thighs, lower arms and legs, dorsum of hands and feet, palms). In conclusion, highly intermittent UVR exposure sites and poor skin visibility presumably correlate with reduced melanoma survival, independent of established tumor characteristics. A limitation of the study was the lack of information on actual individual UVR exposure. This article is protected by copyright. All rights reserved.

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Radiotherapy-assisted tumor selective metronomic oral chemotherapy

Abstract

Chemotherapy have commonly been used in maximum tolerated dose (MTD) to completely eradicate the cancer. However, such treatments often failed due to the complex and dynamic nature of cancer. Therefore, it has been suggested that cancer should be treated as a chronic disease, controlling its growth by providing continuous therapeutic pressure for long-term. Such an approach, however, requires a therapy that is non-toxic and orally available with sufficient potency. Herein, we propose a radiotherapy-assisted orally available metronomic apoptosis-targeted chemotherapy, which delivers doxorubicin continuously to the irradiated tumor with high selectivity while causing minimal toxicities to the normal tissues. DEVD-S-DOX/DCK complex is the anticancer prodrug for our strategy that could selectively release doxorubicin in the irradiated tumor tissue with sufficient oral bioavailability. The prodrug was completely inactive by itself, but displayed potent anticancer activity when coupled with radiotherapy. Consequently, the daily oral administration of DEVD-S-DOX/DCK in combination with the low-dose radiotherapy effectively suppressed the growth of tumor in vivo with no significant systemic toxicities despite that the accumulated dose of doxorubicin exceeded 150 mg/kg. Therefore, the our novel therapy using DEVD-S-DOX/DCK complex is considered as an outstanding treatment option for treating cancer for long-term attributed to its oral availability and low-toxicity profile as well as the potent anticancer effect. This article is protected by copyright. All rights reserved.

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Laparoscopic Versus Open Approach for Intersphincteric Resection—Results from a Tertiary Cancer Center in India

Abstract

The study aims to compare open intersphincteric resection (OISR) with laparoscopic intersphincteric resection (LISR) in terms of short-term oncological and clinical outcomes. This is a retrospective review of a prospectively maintained database including all the patients of rectal cancer who underwent intersphincteric resection (ISR) at Tata Memorial Centre between 1st July 2013 and 30th November 2015. Short-term oncological parameters evaluated included circumferential resection margin involvement (CRM), distal resection margin involvement, and number of nodes harvested. Perioperative outcomes included blood loss, length of hospital stay and 30-day postoperative morbidity and mortality. Chi-square test was used to compare the results between the two groups. Thirty nine cases of OISR and 34 cases of LISR were included in the study. Median BMI was higher in LISR group; otherwise, the two groups were comparable in all aspects. There were no conversions in LISR group. CRM involvement was seen in four patients (10%) in the conventional group compared to none in the LISR group. Median hospital stay was comparable between the two groups. Laparoscopic ISR is safe and can be performed with low conversion rate in selected group of patients.

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Breastfeeding during pregnancy: A systematic review

Publication date: Available online 19 June 2017
Source:Women and Birth
Author(s): G. López-Fernández, M. Barrios, J. Goberna-Tricas, J. Gómez-Benito
BackgroundThe consequences of breastfeeding during pregnancy (BDP) have not been clearly established. Available studies have addressed isolated aspects of this issue using different methodologies, often resulting in contradictory results. To our knowledge, no systematic review has assessed and compared these studies, making it difficult to obtain a clear picture of the consequences of BDP.AimTo review and summarise all the scientific evidence relating to BDP, and determine whether this evidence is sufficient to establish clear implications for the mother, breastmilk, breastfed child, current pregnancy, and ultimately, the newborn.MethodsWe conducted a systematic review of the English and Spanish literature published between 1990 and 2015 using Cinahl, PubMed, IME, CUIDEN, Cochrane Library, Web of Science and PyscINFO.Findings3278 publications were identified from databases, their titles and abstracts were checked to ensure the studies were related to the subject and met the selection criteria. Only 19 studies met all requirements and were included in the review.Conclusions and implicationsData suggest that BDP does not affect the way pregnancies end or even birth weights. However, several questions remain unanswered. Specifically, it is unclear how BDP affects maternal nutritional status in developed countries, the growth and health of breastfed siblings, the composition of breastmilk, or the growth of the newborn after delivery. Further studies of BDP are needed with larger samples, adequate methodology and proper control of the main confounders.



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Response to Editorial, who can be a legitimate author on an article?

Publication date: Available online 19 June 2017
Source:Women and Birth
Author(s): Patricia Jarrett




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Genomic alterations in fatal forms of non-anaplastic thyroid cancer: Identification of MED12 and RBM10 as novel thyroid cancer genes associated with tumor virulence

Purpose. Patients with anaplastic thyroid cancer have a very high death rate. In contrast, deaths from non-anaplastic thyroid cancer are much less common. The genetic alterations in fatal non-anaplastic thyroid cancers have not been reported. <p>Experimental Design. We performed next-generation sequencing of 410 cancer genes from 57 fatal non-anaplastic thyroid primary cancers. Results were compared to The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTC) and to the genomic changes reported in anaplastic thyroid cancer (ATC).</p> <p>Results. There was a very high prevalence of TERT promoter mutations, comparable to that of anaplastic thyroid cancer, and these co-occurred with BRAF and RAS mutations. A high incidence of chromosome 1q gain was seen highlighting its importance in tumor aggressiveness. Two novel fusion genes DLG5-RET and OSBPL1A-BRAF were identified. There was a high frequency of mutations in MED12 and these were mutually exclusive to TERT promoter mutations and also to BRAF and RAS mutations. In addition, a high frequency of mutations in RBM10 were identified and these co-occurred with RAS mutations and PIK3CA mutations. Compared to the PTCs in TCGA, there were higher frequencies of mutations in TP53, POLE, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases.</p> <p>Conclusions. These data support a model whereby fatal non-anaplastic thyroid cancers arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities. The high rate of TERT promoter mutations, MED12 mutations, RBM10 mutations and chromosome 1q gain highlight their likely association with tumor virulence.

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Co-administration of RANKL and CTLA4 antibodies enhances lymphocyte-mediated anti-tumor immunity in mice.

Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice. <br />Results: RANKL blockade improved the efficacy of anti-CTLA4 mAbs against solid tumors and experimental metastases, with regulatory T cell (Treg) depleting anti-CTLA4 mAbs of the mouse IgG2a isotype showing greatest combinatorial activity. The optimal combination depended on the presence of activating Fc receptors and lymphocytes (NK cells for metastatic disease and predominantly CD8⁺ T cells for subcutaneous tumor control), while anti-RANKL alone did not require FcR. The significantly higher T-cell infiltration into solid tumors post anti-RANKL and anti-CTLA-4 was accompanied by increased T-cell effector function (cytokine polyfunctionality), and anti-RANKL activity occurred independently of Treg depletion. The majority of RANKL expression in tumors was on T cells whereas RANK-expressing cells were mostly tumor-associated macrophages (TAMs), with some expression also observed on dendritic cells (DC) and myeloid derived suppressor cells (MDSCs). <br />Conclusions: These results provide a rationale for the further investigation of RANKL-RANK interactions in tumor immunity and a basis for development of translational markers of interest in human clinical trials.

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Phase Ib Study of Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Combination with Pembrolizumab (MK-3475) in Patients with Advanced Solid Tumors

Purpose:  This phase Ib study (NCT02179918) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of utomilumab, a fully human IgG2 mAb agonist of the T-cell costimulatory receptor 4-1BB/CD137 in combination with the humanized, PD-1-blocking IgG4 mAb pembrolizumab in patients with advanced solid tumors. <p>Experimental Design:  Utomilumab (0.45-5.0 mg/kg) and pembrolizumab (2 mg/kg) were administered intravenously every 3 weeks. Utomilumab dose escalation was conducted using the time-to-event-continual reassessment method.</p> <p>Results:  Twenty-three patients received combination treatment with no dose-limiting toxicities. Treatment-emergent adverse events were mostly grades 1-2, without any treatment-related discontinuations. Six (26.1%) patients had confirmed complete or partial responses. Pharmacokinetics and immunogenicity of utomilumab and pembrolizumab were similar when administered alone or in combination. A trend toward higher levels of activated memory/effector peripheral blood CD8⁺ T-cells was observed in responders versus non-responders.</p> <p>Conclusions:  The safety, tolerability, and clinical activity demonstrated by utomilumab in combination with pembrolizumab support further investigation in patients with advanced solid tumors.

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The Serum Analysis of Dampness Syndrome in Patients with Coronary Heart Disease and Chronic Renal Failure Based on the Theory of “Same Syndromes in Different Diseases”

Aim. To analyze the serum metabolites in patients with coronary heart disease (CHD) showing dampness syndrome and patients with chronic renal failure (CRF) showing dampness syndrome and to seek the substance that serves as the underlying basis of dampness syndrome in "same syndromes in different diseases." Methods. Metabolic spectrum by GC-MS was performed using serum samples from 29 patients with CHD showing dampness syndrome and 32 patients with CRF showing dampness syndrome. The principal component analysis and statistical analysis of partial least squares were performed to detect the metabolites with different levels of expression in patients with CHD and CRF. Furthermore, by comparing the VIP value and data mining in METLIN and HMDB, we identified the common metabolites in both patient groups. Results. (1) Ten differential metabolites were found in patients with CHD showing dampness syndrome when compared to healthy subjects. Meanwhile, nine differential metabolites were found in patients with CRF showing dampness syndrome when compared to healthy subjects. (2) There were 9 differential metabolites identified when the serum metabolites of the CHD patients with dampness syndrome were compared to those of CRF patients with dampness syndrome. There were 4 common metabolites found in the serums of both patient groups.

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Effects of Hyperglycemia on Vascular Smooth Muscle Ca2+ Signaling

Diabetes is a complex disease that is characterized with hyperglycemia, dyslipidemia, and insulin resistance. These pathologies are associated with significant cardiovascular implications that affect both the macro- and microvasculature. It is therefore important to understand the effects of various pathologies associated with diabetes on the vasculature. Here we directly test the effects of hyperglycemia on vascular smooth muscle (VSM) Ca2+ signaling in an isolated in vitro system using the A7r5 rat aortic cell line as a model. We find that prolonged exposure of A7r5 cells to hyperglycemia (weeks) is associated with changes to Ca2+ signaling, including most prominently an inhibition of the passive ER Ca2+ leak and the sarcoplasmic reticulum Ca2+-ATPase (SERCA). To translate these findings to the in vivo condition, we used primary VSM cells from normal and diabetic subjects and find that only the inhibition of the ER Ca2+ leaks replicates in cells from diabetic donors. These results show that prolonged hyperglycemia in isolation alters the Ca2+ signaling machinery in VSM cells. However, these alterations are not readily translatable to the whole organism situation where alterations to the Ca2+ signaling machinery are different.

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Bone Marrow Mesenchymal Stem Cells Inhibit the Function of Dendritic Cells by Secreting Galectin-1

This study aimed to investigate whether bone marrow-derived mesenchymal stem cells (BM-MSCs) can inhibit function of dendritic cells (DCs) by secreting Galectin-1 (Gal-1). BM-MSCs have been shown to inhibit the maturation and function of DCs, further inhibiting the activation and proliferation of T cells. However, the detailed mechanism remains unknown. In this current study, MSCs and DCs derived from mouse bone marrow were cocultured using Transwell culture plates under different in vitro conditions. The results showed that as the ratio of MSC to DC of the coculture system increased and the coculture time of the two cells prolonged, the concentrations of Gal-1, interleukin- (IL-) 10, and IL-12 in the supernatants were increased and the protein expression of Gal-1 on and within DCs was also enhanced. The phosphorylation of extracellular signal-regulated kinase (ERK) pathway in DCs was boosted, whereas p38 mitogen-activated protein kinase (MAPK) pathway phosphorylation was weakened. Meanwhile, the expression of costimulatory molecules on the surface of DCs was decreased, and the proliferative effect of DCs on allogeneic T cells was also decreased. Therefore, this present study indicated that Gal-1 secreted from MSCs upregulated expression of Gal-1 and stimulated formation of tolerance immunophenotype on DCs, where the underlying mechanism was the regulation of the MAPK signaling pathway in DCs, thereby inhibiting the function of DCs.

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Targeting Nectin-4 in Bladder Cancer [News in Brief]

Efficacy seen with enfortumab vedotin, even in patients with disease refractory to immune checkpoint blockade.

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Concurrent Neoadjuvant Chemotherapy and Radiotherapy in Locally Advanced Breast Cancer

This prospective phase II trial recruited thirty-two patients with locally advanced breast cancer to receive neoadjuvant radiosensitizing chemotherapy with concurrent radiation. Patients were matched to a concurrent cohort treated with neoadjuvant chemotherapy, mastectomy then radiation. Patients showed significantly improved pathological complete response, but no statistically significant difference in survival. A prospective randomized trial is warranted using another radiosensitizer to exploit this improved response with reduced toxicity.

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Magnetic Resonance Image Guided Adaptive Brachytherapy in Locally Advanced Cervical Cancer: An Experience from a Tertiary Cancer Centre in a low-middle income country setting

To determine the clinical impact of MR image-guided adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC; stage II&III) in a tertiary care cancer hospital in a low middle income country (LMIC) setting.

http://ift.tt/2sTTMbA

Evaluation of the Effects of Prostate Radiotherapy on Occludin Expression and Ultrasonography Characteristics of the Bladder

This study aimed to evaluate the effects of radiation dose in prostate radiotherapy (RT) on occludin expression and ultrasonography characteristics of the bladder.

http://ift.tt/2sTN6u9

Multisource Rotating Shield Brachytherapy Apparatus for Prostate Cancer

To present a novel multisource rotating shield brachytherapy (RSBT) apparatus for the simultaneous precise angular and linear positioning of partially-shielded 153Gd brachytherapy sources in interstitial needles for the treatment of locally-advanced prostate cancer. It is designed to lower the dose to nearby healthy tissues, the urethra in particular, relative to conventional high-dose-rate brachytherapy (HDR-BT) techniques.

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Brief Opinion on Pulling Down Briefs…

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Superiority in robustness of multi-field optimization over single-field optimization for pencil-beam proton therapy for oropharynx carcinoma: an enhanced robustness analysis

To compare the difference in robustness of single-field (SFO) and robust multi-field optimized (rMFO) proton plans for oropharynx carcinoma patients by improved robustness analysis.

http://ift.tt/2rARUAE

Burnout Evaluation of Radiation Residents Nationwide (BERRN): Results of a Survey of United States Residents

A survey of US radiation oncology residents incorporating the Maslach Burnout Index-Human Services Survey (MBI—HSS) assessed symptoms of burnout and resident/program-specific factors associated with burnout. Completed surveys were available for 205 residents and revealed a 33.1% rate of burnout. This burnout rate is consistent with previous surveys conducted among oncology practicing physicians and residents. Further studies and interventions targeting burnout among radiation oncology residents may reduce downstream consequences.

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Simple Expression Domains Are Regulated by Discrete CRMs During Drosophila Oogenesis

Eggshell patterning has been extensively studied in Drosophila melanogaster. However, the cis-regulatory modules (CRMs), which control spatiotemporal expression of these patterns, are vastly unexplored. The FlyLight collection contains over 7,000 intergenic and intronic DNA fragments that, if containing CRMs, can drive the transcription factor GAL4. We cross-listed the 84 genes known to be expressed during D. melanogaster oogenesis with the ~1200 listed genes of the FlyLight collection, and found 22 common genes that are represented by 281 FlyLight fly lines. Of these lines, 54 show expression patterns during oogenesis when crossed to an UAS-GFP reporter. Of the 54 lines, 16 recapitulate the full or partial pattern of the associated gene pattern. Interestingly, while the average DNA fragment size is ~3kb in length, the vast majority of fragments show one type of a spatiotemporal pattern in oogenesis. Mapping the distribution of all 54 lines, we found a significant enrichment of CRMs in the first intron of the associated genes' model. In addition, we demonstrate the use of different anteriorly active FlyLight lines as tools to disrupt eggshell patterning in a targeted manner. Our screen provides further evidence that complex gene-patterns are assembled combinatorially by different CRMs controlling the expression of genes in simple domains.

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Diagnostic accuracy of EUS compared with MRCP in detecting choledocholithiasis: a meta-analysis of diagnostic test accuracy of head-to-head studies

There is a wide range of reported sensitivity and specificity for endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of the choledocholithiasis with lack of a proper meta-analysis of diagnostic test accuracy (DTA) using head-to-head comparison. Here, we aimed at comparing the diagnostic accuracy of EUS and MRCP in detecting choledocholithiasis using appropriate methodology recommended by the Cochrane Collaboration.

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The Pediatric Medical Student Research Forum: Fostering Interest in Pediatric Research

Ensuring a pediatric research workforce is critical for improving health and healthcare for children.1-7 As such, encouraging interest and recognizing pediatric research activities is important in stimulating medical students to pursue academic careers in pediatrics. Before the creation of the Pediatric Medical Student Research Forum (PMSRF) 3 years ago, there were no unified national venues dedicated exclusively to medical students that focused on pediatric-related research.

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