bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of stem cell transplant and maintenance therapy in plasma cell disorders
Authors: McCarthy Philip L. , Holstein Sarah A.
Published: December 2016

Autologous stem cell transplant (ASCT) has been an important component of therapy for myeloma patients eligible for high-dose chemotherapy. Recent studies comparing early transplant to low-dose chemotherapy support the continued use of ASCT as consolidation following induction therapy, even in the era of immunomodulatory drugs, proteasome inhibitors, and other novel agents. Despite the marked improvements in outcomes with this approach, most patients will eventually experience disease progression. Thus, inclusion of post-ASCT consolidation/maintenance strategies is used to improve long-term disease control. Multiple randomized studies support the use of lenalidomide maintenance therapy following ASCT. The next generation of clinical trials will incorporate novel agents such as monoclonal antibodies, proteasome inhibitors, and other novel pathway modulatory agents into post-ASCT treatment strategies with the goal of achieving even deeper responses and longer durations of disease control.
Checkpoint inhibition in myeloma
Authors: Benson Don M.
Published: December 2016

Historically, attempts at cancer immunotherapy have emphasized strategies designed to stimulate or augment the immune system into action. In the past decade, a complementary approach has developed, that of releasing immune cells from inhibitory restraint. Discoveries in the fundamental biology of how immunity is regulated, how the immune system interfaces with malignancy, and how cancer cells may exploit these processes to evade detection have all been translated into the rapidly growing field of therapeutic immune checkpoint inhibition for cancer. Myeloma is a malignancy associated with significant immune dysfunction imparted both by the disease itself as well as by many of the immunosuppressive therapies that have been used in the past. The growing body of preclinical data regarding immunoregulatory mechanisms that appear active in myeloma has begun to be translated to clinical trials targeting these signaling axes. This review will attempt to summarize the current understanding of the basic biology of several immune checkpoint pathways that may be important in myeloma and provide an up-to-date overview of recent and ongoing clinical trials of immune checkpoint inhibitors in myeloma. Finally, several current challenges and possible future directions of immune checkpoint blockade in myeloma will be reviewed.
Non-Hodgkin lymphoma across the pediatric and adolescent and young adult age spectrum
Authors: Sandlund John T. , Martin Mike G.
Published: December 2016

The non-Hodgkin lymphomas (NHLs) occurring in children and adolescents and young adults (AYA) are characterized by various age-related differences in tumor biology and survival. Children generally present with high-grade lymphomas, such as Burkitt lymphoma, diffuse large B-cell lymphoma, lymphoblastic lymphoma, and anaplastic large cell lymphoma, whereas low-grade histologic subtypes, such as follicular lymphoma, occur more frequently with increasing age. Treatment outcome for children with NHL is generally superior to that observed in adults. Factors contributing to this discrepancy include psychosocial factors, patient factors, and differences in tumor biology and therapy. These factors will be reviewed, with particular attention to the biological features of diffuse large B-cell lymphoma and anaplastic large cell lymphoma and corresponding therapeutic challenges. Novel targeting agents have been developed, which have been shown to be active in some patients. There is clearly a need for treatment protocols with eligibility criteria that cover the full span of the pediatric and AYA age range and that incorporate detailed molecular characterization of the tumors.
Sickle cell disease: when and how to transfuse
Authors: Howard Jo
Published: December 2016

Blood transfusion remains an important therapeutic intervention in patients with sickle cell disease (SCD), aiming to both increase the oxygen carrying capacity of blood and to reduce the complications of vaso-occlusion. Simple, manual exchange and automated exchange can be effective in reducing the acute and chronic complications of SCD, and the advantages and disadvantages of each methodology mean they all have a role in different situations. Evidence for the role of emergency transfusion in the management of the acute complications of SCD, including acute pain and acute chest syndrome, comes from observational data. Several important randomized controlled trials have shown the efficacy of transfusion in primary and secondary stroke prevention in patients with SCD but, outside these areas, clinical practice lacks a clear evidence base. Evidence for the role of long-term transfusion in the prevention of the non-neurologic chronic complications of SCD comes from analysis of secondary outcomes of these randomized trials and from observational data. In view of the paucity of data, the risks and benefits of transfusion should be fully discussed with patients/families before a long-term transfusion program is commenced. Evidence is only available for the role of preoperative transfusion or for prophylactic transfusion through pregnancy in certain situations, and the role of transfusions outside these situations is discussed. Questions about when and how to transfuse in SCD remain and will need further randomized trials to provide answers.
Prevention of central nervous system sequelae in sickle cell disease without evidence from randomized controlled trials: the case for a team-based learning collaborative
Authors: DeBaun Michael R. , King Allison A.
Published: December 2016

Since 1998, the National Institutes of Health has funded 5 randomized controlled trials (RCTs) for primary and secondary prevention of strokes in children with sickle cell anemia (SCA). In a systematic fashion, these trials have significantly advanced the care of children with SCA. In the absence of an RCT, clinicians are often compelled to make decisions at the bedside, based on experience, observational studies, and principles of hematology. We will provide an initial example that describes how a team-based, learning collaborative developed a multisite standard care protocol with a low budget (<$10 000 per year) to overcome the intrinsic limitations of advancing the care of neurologic complications in sickle cell disease (SCD). The critical components of this approach include: (1) regular meetings with the multidisciplinary team from multiple sites; (2) consensus regarding the best evidence-based neurologic management in multiple SCD centers; (3) an Institutional Review Board-approved protocol based on consensus standard care; (4) minimizing and ensuring accurate data collection; and most importantly, (5) a spirit of collaboration to improve the care of individuals with SCD. Four common neurologic problems and strategies for management in children and adults with SCD will be discussed: (1) secondary stroke prevention in high-income countries; (2) primary stroke prevention in low- and middle-income countries (LMICs); (3) poor academic performance in students; and (4) cognitive disability in adults. With a commitment to a team-based learning collaborative, incremental advances are possible for the neurologic care of children and adults with SCD.
New therapies for hemophilia
Authors: Pipe Steven W.
Published: December 2016

Individuals with severe hemophilia have benefitted from 5 decades of advances that have led to widespread availability of safe and efficacious factors VIII and IX, a multidisciplinary integrated care model through a network of specialized hemophilia treatment centers, and aggressive introduction of prophylactic replacement therapy to prevent bleeding and preserve joint health. Yet, there are remaining challenges and treatment gaps which have prevented complete abrogation of all joint bleeding, and progressive joint deterioration may continue in some affected individuals over the course of a lifetime. Some of these challenges can now be addressed with recombinant clotting factors with extended half-life that may improve adherence to prophylaxis regimens through more convenient infusion schedules, maintain higher plasma levels for longer when clinically necessary, and allow for better adaptation to individual phenotypic and pharmacokinetic variability. Real-world case studies will be presented that illustrate practical application of these newly approved therapies in clinical practice and the clinical trial data that have demonstrated the potential for improved clinical outcomes by implementing these strategies.
What is the role of hydroxychloroquine in reducing thrombotic risk in patients with antiphospholipid antibodies?
Authors: Wang Tzu-Fei , Lim Wendy
Published: December 2016

A 35-year-old man presents with an acute unprovoked deep vein thrombosis of the left lower extremity. He is treated with anticoagulation and elects to discontinue treatment after 6 months. He subsequently develops polyarthralgias, fatigue, and a malar rash, and a diagnosis of systemic lupus erythematosus is made based on laboratory and clinical findings. Additional laboratory testing reveals persistent triple positive antiphospholipid antibodies, including lupus anticoagulant, high titer anticardiolipin antibodies, and anti–β2-glycoprotein I antibodies. The patient is reinitiated on anticoagulation, and the patient’s rheumatologist inquires if the addition of hydroxychloroquine could help to prevent recurrent thrombosis.
Nontransplant therapy for bone marrow failure
Authors: Townsley Danielle M. , Winkler Thomas
Published: December 2016

Nontransplant therapeutic options for acquired and constitutional aplastic anemia have significantly expanded during the last 5 years. In the future, transplant may be required less frequently. That trilineage hematologic responses could be achieved with the single agent eltrombopag in refractory aplastic anemia promotes new interest in growth factors after years of failed trials using other growth factor agents. Preliminary results adding eltrombopag to immunosuppressive therapy are promising, but long-term follow-up data evaluating clonal evolution rates are required before promoting its standard use in treatment-naive disease. Danazol, which is traditionally less preferred for treating cytopenias, is capable of preventing telomere attrition associated with hematologic responses in constitutional bone marrow failure resulting from telomere disease.
Transplantation for bone marrow failure: current issues
Authors: Peffault de Latour Régis
Published: December 2016

The preferred treatment of idiopathic aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)–identical sibling donor. Transplantation from a well-matched unrelated donor (MUD) may be considered for patients without a sibling donor after failure of immunosuppressive therapy, as may alternative transplantation (mismatched, cord blood or haplo-identical HSCT) for patients without a MUD. HSCT may also be contemplated for congenital disorders in cases of pancytopenia or severe isolated cytopenia. Currently, HSCT aims are not only to cure patients but also to avoid long-term complications, notably chronic graft-versus-host disease (GVHD), essential for a good quality of life long term. This paper summarizes recent advances in HSCT for idiopathic and inherited AA disorders. The effect of age on current transplantation outcomes, the role of transplantation in paroxysmal nocturnal hemoglobinuria, and the prevention of GVHD are also discussed. Emerging strategies regarding the role of up-front unrelated donor and alternative donor HSCT in idiopathic AA, along with advances in the treatment of clonal evolution in Fanconi anemia, are also examined.
Development and Evaluation of the Tigriopus Course-Based Undergraduate Research Experience: Impacts on Students’ Content Knowledge, Attitudes, and Motivation in a Majors Introductory Biology Course
Authors: Olimpo Jeffrey T. , Fisher Ginger R. , DeChenne-Peters Sue Ellen
Published: December 2016

Within the past decade, course-based undergraduate research experiences (CUREs) have emerged as a viable mechanism to enhance novices’ development of scientific reasoning and process skills in the science, technology, engineering, and mathematics disciplines. Recent evidence within the bioeducation literature suggests that student engagement in such experiences not only increases their appreciation for and interest in scientific research but also enhances their ability to “think like a scientist.” Despite these critical outcomes, few studies have objectively explored CURE versus non-CURE students’ development of content knowledge, attitudes, and motivation in the discipline, particularly among nonvolunteer samples. To address these concerns, we adopted a mixed-methods approach to evaluate the aforementioned outcomes following implementation of a novel CURE in an introductory cell/molecular biology course. Results indicate that CURE participants exhibited more expert-like outcomes on these constructs relative to their non-CURE counterparts, including in those areas related to self-efficacy, self-determination, and problem-solving strategies. Furthermore, analysis of end-of-term survey data suggests that select features of the CURE, such as increased student autonomy and collaboration, mediate student learning and enjoyment. Collectively, this research provides novel insights into the benefits achieved as a result of CURE participation and can be used to guide future development and evaluation of authentic research opportunities.
Making the Grade: Using Instructional Feedback and Evaluation to Inspire Evidence-Based Teaching
Authors: Brickman Peggy , Gormally Cara , Martella Amedee Marchand
Published: December 2016

Typically, faculty receive feedback about teaching via two mechanisms: end-of-semester student evaluations and peer observation. However, instructors require more sustained encouragement and constructive feedback when implementing evidence-based teaching practices. Our study goal was to characterize the landscape of current instructional-feedback practices in biology and uncover faculty perceptions about these practices. Findings from a national survey of 400 college biology faculty reveal an overwhelming dissatisfaction with student evaluations, regardless of self-reported teaching practices, institution type, or position. Faculty view peer evaluations as most valuable, but less than half of faculty at doctoral-granting institutions report participating in peer evaluation. When peer evaluations are performed, they are more supportive of evidence-based teaching than student evaluations. Our findings reveal a large, unmet desire for greater guidance and assessment data to inform pedagogical decision making. Informed by these findings, we discuss alternate faculty-vetted feedback strategies for providing formative instructional feedback.
Using Student Writing and Lexical Analysis to Reveal Student Thinking about the Role of Stop Codons in the Central Dogma
Authors: Prevost Luanna B. , Smith Michelle K. , Knight Jennifer K.
Published: December 2016

Previous work has shown that students have persistent difficulties in understanding how central dogma processes can be affected by a stop codon mutation. To explore these difficulties, we modified two multiple-choice questions from the Genetics Concept Assessment into three open-ended questions that asked students to write about how a stop codon mutation potentially impacts replication, transcription, and translation. We then used computer-assisted lexical analysis combined with human scoring to categorize student responses. The lexical analysis models showed high agreement with human scoring, demonstrating that this approach can be successfully used to analyze large numbers of student written responses. The results of this analysis show that students’ ideas about one process in the central dogma can affect their thinking about subsequent and previous processes, leading to mixed models of conceptual understanding.
Toward High School Biology: Helping Middle School Students Understand Chemical Reactions and Conservation of Mass in Nonliving and Living Systems
Authors: Herrmann-Abell Cari F. , Koppal Mary , Roseman Jo Ellen
Published: December 2016

Modern biology has become increasingly molecular in nature, requiring students to understand basic chemical concepts. Studies show, however, that many students fail to grasp ideas about atom rearrangement and conservation during chemical reactions or the application of these ideas to biological systems. To help provide students with a better foundation, we used research-based design principles and collaborated in the development of a curricular intervention that applies chemistry ideas to living and nonliving contexts. Six eighth grade teachers and their students participated in a test of the unit during the Spring of 2013. Two of the teachers had used an earlier version of the unit the previous spring. The other four teachers were randomly assigned either to implement the unit or to continue teaching the same content using existing materials. Pre- and posttests were administered, and the data were analyzed using Rasch modeling and hierarchical linear modeling. The results showed that, when controlling for pretest score, gender, language, and ethnicity, students who used the curricular intervention performed better on the posttest than the students using existing materials. Additionally, students who participated in the intervention held fewer misconceptions. These results demonstrate the unit’s promise in improving students’ understanding of the targeted ideas.
Characterizing Student Perceptions of and Buy-In toward Common Formative Assessment Techniques
Authors: Brazeal Kathleen R. , Brown Tanya L. , Couch Brian A.
Published: December 2016

Formative assessments (FAs) can occur as preclass assignments, in-class activities, or postclass homework. FAs aim to promote student learning by accomplishing key objectives, including clarifying learning expectations, revealing student thinking to the instructor, providing feedback to the student that promotes learning, facilitating peer interactions, and activating student ownership of learning. While FAs have gained prominence within the education community, we have limited knowledge regarding student perceptions of these activities. We used a mixed-methods approach to determine whether students recognize and value the role of FAs in their learning and how students perceive course activities to align with five key FA objectives. To address these questions, we administered a midsemester survey in seven introductory biology course sections that were using multiple FA techniques. Overall, responses to both open-ended and closed-ended questions revealed that the majority of students held positive perceptions of FAs and perceived FAs to facilitate their learning in a variety of ways. Students consistently considered FA activities to have accomplished particular objectives, but there was greater variation among FAs in how students perceived the achievement of other objectives. We further discuss potential sources of student resistance and implications of these results for instructor practice.
The Design and Transformation of Biofundamentals: A Nonsurvey Introductory Evolutionary and Molecular Biology Course
Authors: Klymkowsky Michael W. , Rentsch Jeremy D. , Begovic Emina , Cooper Melanie M.
Published: December 2016

Many introductory biology courses amount to superficial surveys of disconnected topics. Often, foundational observations and the concepts derived from them and students’ ability to use these ideas appropriately are overlooked, leading to unrealistic expectations and unrecognized learning obstacles. The result can be a focus on memorization at the expense of the development of a meaningful framework within which to consider biological phenomena. About a decade ago, we began a reconsideration of what an introductory course should present to students and the skills they need to master. The original Web-based course’s design presaged many of the recommendations of the Vision and Change report; in particular, a focus on social evolutionary mechanisms, stochastic (evolutionary and molecular) processes, and core ideas (cellular continuity, evolutionary homology, molecular interactions, coupled chemical reactions, and molecular machines). Inspired by insights from the Chemistry, Life, the Universe & Everything general chemistry project, we transformed the original Web version into a (freely available) book with a more unified narrative flow and a set of formative assessments delivered through the beSocratic system. We outline how student responses to course materials are guiding future course modifications, in particular a more concerted effort at helping students to construct logical, empirically based arguments, explanations, and models.
Student Buy-In to Active Learning in a College Science Course
Authors: Cavanagh Andrew J. , Aragón Oriana R. , Chen Xinnian , Couch Brian A. , Durham Mary F. , Bobrownicki Aiyana , Hanauer David I. , Graham Mark J.
Published: December 2016

The benefits of introducing active learning in college science courses are well established, yet more needs to be understood about student buy-in to active learning and how that process of buy-in might relate to student outcomes. We test the exposure–persuasion–identification–commitment (EPIC) process model of buy-in, here applied to student (n = 245) engagement in an undergraduate science course featuring active learning. Student buy-in to active learning was positively associated with engagement in self-regulated learning and students’ course performance. The positive associations among buy-in, self-regulated learning, and course performance suggest buy-in as a potentially important factor leading to student engagement and other student outcomes. These findings are particularly salient in course contexts featuring active learning, which encourage active student participation in the learning process.
Childhood maltreatment and characteristics of adult depression: Meta-analysis
Authors: Nelson Janna , Klumparendt Anne , Doebler Philipp , Ehring Thomas
Published: December 2016

Background

Childhood maltreatment has been discussed as a risk factor for the development and maintenance of depression.

Aims

To examine the relationship between childhood maltreatment and adult depression with regard to depression incidence, severity, age at onset, course of illness and treatment response.

Method

We conducted meta-analyses of original articles reporting an association between childhood maltreatment and depression outcomes in adult populations.

Results

In total, 184 studies met inclusion criteria. Nearly half of patients with depression reported a history of childhood maltreatment. Maltreated individuals were 2.66 (95% CI 2.38–2.98) to 3.73 (95% CI 2.88–4.83) times more likely to develop depression in adulthood, had an earlier depression onset and were twice as likely to develop chronic or treatment-resistant depression. Depression severity was most prominently linked to childhood emotional maltreatment.

Conclusions

Childhood maltreatment, especially emotional abuse and neglect, represents a risk factor for severe, early-onset, treatment-resistant depression with a chronic course.
Depression screening with patient-targeted feedback in cardiology: DEPSCREEN-INFO randomised clinical trial
Authors: Löwe Bernd , Blankenberg Stefan , Wegscheider Karl , König Hans-Helmut , Walter Dirk , Murray Alexandra M. , Gierk Benjamin , Kohlmann Sebastian
Published: December 2016

Background

International guidelines advocate depression screening in patients with coronary heart disease (CHD) and other chronic illnesses, but evidence is lacking.

Aims

To test the differential efficacy of written patient-targeted feedback v. no written patient feedback after depression screening.

Method

Patients with CHD or hypertension from three cardiology settings were randomised and screened for depression (ClinicalTrials.gov Identifier: NCT01879111). Compared with the control group, where only cardiologists received written feedback, in the intervention group both cardiologists and patients received written feedback regarding depression status. Depression severity was measured 1 month (primary outcome) and 6 months after screening.

Results

The control group (n = 220) and the patient-feedback group (n = 155) did not differ in depression severity 1 month after screening. Six months after screening, the patient-feedback group showed significantly greater improvements in depression severity and was twice as likely to seek information about depression compared with the control group.

Conclusions

Patient-targeted feedback in addition to screening has a significant but small effect on depression severity after 6 months and may encourage patients to take an active role in the self-management of depression.
Preoperative Echocardiographic Indices of Diastolic Dysfunction and Brain Natriuretic Peptide in Predicting Postoperative Atrial Fibrillation After Noncardiac Surgery
Authors: Brecher Oren , Gulati Harleena , Roistacher Nancy , Zhang Hao , Shi Weiji , Thaler Howard T. , Amar David
Published: December 2016

BACKGROUND:

We have shown previously that either echocardiographic indices of diastolic dysfunction or increased preoperative brain natriuretic peptide (BNP) predict postoperative atrial fibrillation (POAF). Because these 2 predictors of POAF have not been evaluated together, our goal was to further elucidate their concurrent role in patients undergoing noncardiac thoracic surgery.

METHODS:

We retrospectively identified 191 patients who had a preoperative transthoracic echocardiogram and serum BNP level collected as part of routine care before major lung or esophageal resection. Clinical and echocardiographic data were compared between patients who did or did not develop POAF (>5 minutes), and prognostic factors for POAF were identified.

RESULTS:

Univariate associations with POAF (41 of 191; 22% patients) included older age (P = .04), male sex (P = .01), hypertension (P = .03), increased body mass index (P = .01), and prolonged transmitral flow deceleration time (P < .0001), whereas BNP was not statistically significant (P = .07). Stepwise logistic regression analysis showed that both increasing transmitral flow deceleration time (continuous data log base 2 transformed; odds ratio, 16.05; 95% confidence interval, 3.74–68.96; P = .0002) and left atrial diastolic volume index (continuous data log base 2 transformed; odds ratio, 3.29; 95% confidence interval, 1.22–8.91; P = .02) were independent risk factors of POAF (area under the receiver operating characteristic curve = 0.73). There was no significant interaction between BNP and the 2 independent variables (P = .60, and P = .90), respectively.

CONCLUSIONS:

In a cohort of patients who had echocardiography and BNP measurements before undergoing major thoracic surgery, this study showed that when evaluated together greater preoperative left atrial diastolic volume index and transmitral flow deceleration time but not BNP levels were independent predictors for POAF.
Resident Physicians Improve Nontechnical Skills When on Operating Room Management and Leadership Rotation
Authors: Cole Devon C. , Giordano Christopher R. , Vasilopoulos Terrie , Fahy Brenda G.
Published: December 2016

BACKGROUND:

Anesthesiology residency primarily emphasizes the development of medical knowledge and technical skills. Yet, nontechnical skills (NTS) are also vital to successful clinical practice. Elements of NTS are communication, teamwork, situational awareness, and decision making.

METHODS:

The first 10 consecutive senior residents who chose to participate in this 2-week elective rotation of operating room (OR) management and leadership training were enrolled in this study, which spanned from March 2013 to March 2015. Each resident served as the anesthesiology officer of the day (AOD) and was tasked with coordinating OR assignments, managing care for 2 to 4 ORs, and being on call for the trauma OR; all residents were supervised by an attending AOD. Leadership and NTS techniques were taught via a standardized curriculum consisting of leadership and team training articles, crisis management text, and daily debriefings. Resident self-ratings and attending AOD and charge nurse raters used the Anaesthetists’ Non-Technical Skills (ANTS) scoring system, which involved task management, situational awareness, teamwork, and decision making. For each of the 10 residents in their third year of clinical anesthesiology training (CA-3) who participated in this elective rotation, there were 14 items that required feedback from resident self-assessment and OR raters, including the daily attending AOD and charge nurse. Results for each of the items on the questionnaire were compared between the beginning and the end of the rotation with the Wilcoxon signed-rank test for matched samples. Comparisons were run separately for attending AOD and charge nurse assessments and resident self-assessments. Scaled rankings were analyzed for the Kendall coefficient of concordance (ω) for rater agreement with associated χ2 and P value.

RESULTS:

Common themes identified by the residents during debriefings were recurrence of challenging situations and the skills residents needed to instruct and manage clinical teams. For attending AOD and charge nurse assessments, resident performance of NTS improved from the beginning to the end of the rotation on 12 of the 14 NTS items (P < .05), whereas resident self-assessment improved on 3 NTS items (P < .05). Interrater reliability (across the charge nurse, resident, and AOD raters) ranged from ω = .36 to .61 at the beginning of the rotation and ω = .27 to .70 at the end of the rotation.

CONCLUSIONS:

This rotation allowed for teaching and resident assessment to occur in a way that facilitated resident education in several of the skills required to meet specific milestones. Resident physicians are able to foster NTS and build a framework for clinical leadership when completing a 2-week senior elective as an OR manager.
Effectiveness of Epidural Analgesia, Continuous Surgical Site Analgesia, and Patient-Controlled Analgesic Morphine for Postoperative Pain Management and Hyperalgesia, Rehabilitation, and Health-Related Quality of Life After Open Nephrectomy: A Prospective, Randomized, Controlled Study
Authors: Capdevila Xavier , Moulard Sebastien , Plasse Christian , Peshaud Jean-Luc , Molinari Nicolas , Dadure Christophe , Bringuier Sophie
Published: December 2016

BACKGROUND:

There is no widely recognized effective technique to optimally reduce pain scores and prevent persistent postoperative pain after nephrectomy. We compared continuous surgical site analgesia (CSSA), epidural analgesia (EA), and a control group (patient-controlled analgesic morphine) in patients undergoing open nephrectomy.

METHODS:

Sixty consecutive patients were randomized to be part of EA, CSSA, or control groups postoperatively for 72 hours. All patients received patient-controlled analgesic morphine, if needed. Hyperalgesia was assessed on the first, second, and third postoperative days. Chronic pain characteristics and quality of life were analyzed at 1 and 3 months. The primary outcome was the pain score at 24 hours. Secondary outcomes were morphine consumption, postoperative rehabilitation, hyperalgesia, chronic pain incidence, and quality-of-life parameters.

RESULTS:

At 24 hours, mean ± standard deviation pain values at rest (2.4 ± 1.7, 2.2 ± 1.2, and 4.2 ± 1.2, respectively, in EA, CSSA, and control groups, P <.001) and during coughing was lower in the EA and CSSA groups. Total morphine consumption was higher in the control group. Rehabilitation parameters improved sooner in the EA and CSSA groups. Median values of area of hyperalgesia differed at 48 hours between the EA group and the control group (36.4 cm2) and (52 cm2) (P = .01) and at 72 hours among the EA group, CSSA group, and the control group (40 cm2, 39.5 cm2, and 59 cm2, respectively; P = .002). CSSA reduced the severity of pain and hyperalgesia at 1 month and optimized quality of life 3 months after surgery (role physical scores, P = .005).

CONCLUSIONS:

CSSA and EA significantly improve postoperative analgesia, reduce postoperative morphine consumption, area of wound hyperalgesia, and accelerate patient rehabilitation after open nephrectomy. CSSA significantly reduces the severity of residual pain 1 month after surgery and optimizes quality-of-life parameters 3 months after surgery.
Challenges of Anesthesia in Low- and Middle-Income Countries: A Cross-Sectional Survey of Access to Safe Obstetric Anesthesia in East Africa
Authors: Epiu Isabella , Tindimwebwa Jossy Verel Bahe , Mijumbi Cephas , Chokwe Thomas M. , Lugazia Edwin , Ndarugirire Francois , Twagirumugabe Theogene , Dubowitz Gerald
Published: December 2016

BACKGROUND:

The United Nations 2015 Millennium Development Goals targeted a 75% reduction in maternal mortality. However, in spite of this goal, the number of maternal deaths per 100,000 live births remains unacceptably high across Sub-Saharan Africa. Because many of these deaths could likely be averted with access to safe surgery, including cesarean delivery, we set out to assess the capacity to provide safe anesthetic care for mothers in the main referral hospitals in East Africa.

METHODS:

A cross-sectional survey was conducted at 5 main referral hospitals in East Africa: Uganda, Kenya, Tanzania, Rwanda, and Burundi. Using a questionnaire based on the World Federation of the Societies of Anesthesiologists (WFSA) international guidelines for safe anesthesia, we interviewed anesthetists in these hospitals, key informants from the Ministry of Health and National Anesthesia Society of each country (Supplemental Digital Content, http://links.lww.com/AA/B561).

RESULTS:

Using the WFSA checklist as a guide, none of respondents had all the necessary requirements available to provide safe obstetric anesthesia, and only 7% reported adequate anesthesia staffing. Availability of monitors was limited, and those that were available were often nonfunctional. The paucity of local protocols, and lack of intensive care unit services, also contributed significantly to poor maternal outcomes. For a population of 142.9 million in the East African community, there were only 237 anesthesiologists, with a workforce density of 0.08 in Uganda, 0.39 in Kenya, 0.05 in Tanzania, 0.13 in Rwanda, and 0.02 anesthesiologists in Burundi per 100,000 population in each country.

CONCLUSIONS:

We identified significant shortages of both the personnel and equipment needed to provide safe anesthetic care for obstetric surgical cases across East Africa. There is a need to increase the number of physician anesthetists, to improve the training of nonphysician anesthesia providers, and to develop management protocols for obstetric patients requiring anesthesia. This will strengthen health systems and improve surgical outcomes in developing countries. More funding is required for training physician anesthetists if developing countries are to reach the targeted specialist workforce density of the Lancet Commission on Global Surgery of 20 surgical, anesthetic, and obstetric physicians per 100,000 population by 2030.
Isoflurane Impairs Motor Function Recovery by Increasing Neuroapoptosis and Degeneration During Spinal Ischemia–Reperfusion Injury in Rats
Authors: Fang Shih-Yuan , Lee Jung-Shun , Roan Jun-Neng , Tsai Yu-Chuan , Lam Chen-Fuh
Published: December 2016

BACKGROUND:

Spinal cord ischemia (SCI) leads to variable degrees of neurologic deficit in patients undergoing major cardiovascular surgery. The effect of intraoperative neuroprotection against SCI and the subsequent ischemia–reperfusion injury is still limited. Because isoflurane is a commonly used anesthetic agent during major operation, and its neuroprotective and neurotoxicity effects have both been discussed, this study aimed to investigate the effect of isoflurane on the spinal cord’s functional recovery in a rat model of cord ischemia.

METHODS:

Rats were randomly anesthetized by parenteral anesthetic (Zoletil®) and isoflurane (0% and 1.5% v/v in oxygen). Cord ischemia was induced by cross-clamping of thoracic aorta at the level of T5, and cord perfusion was resumed after 25 minutes. The motor function was assessed independently up to 48 hours after reperfusion. Spinal cords were harvested and analyzed for molecular and histologic changes.

RESULTS:

The locomotor rating scale was significantly reduced in rats that received isoflurane treatment during SCI at 12 to 48 hours after reperfusion. Isoflurane enhanced the expression of heme oxygenase-1, glial fibrillary acidic protein, cleaved caspase-3, and Iba-1 in the spinal cord. Increased apoptotic cells and the presence of axonal damage were also observed in the histologic sections.

CONCLUSION:

Our results demonstrate that the administration of inhaled isoflurane in spinal cord ischemia–reperfusion injury impairs the recovery of motor function. This response is associated with the neuronal apoptosis and degeneration. This study highlights the potential adverse effect of isoflurane on the functional recovery of ischemic spinal cord during major aortic surgery.
Cardiomyocyte specific expression of the nuclear matrix protein, CIZ1, stimulates production of mononucleated cells with an extended window of proliferation in the postnatal mouse heart
Authors: Bageghni Sumia A. , Frentzou Georgia A. , Drinkhill Mark J. , Mansfield William , Coverley Dawn , Ainscough Justin F. X.
Published: December 2016

Myocardial injury in mammals leads to heart failure through pathological cardiac remodelling that includes hypertrophy, fibrosis and ventricular dilatation. Central to this is inability of the mammalian cardiomyocyte to self-renew due to entering a quiescent state after birth. Modulation of the cardiomyocyte cell-cycle after injury is therefore a target mechanism to limit damage and potentiate repair and regeneration. Here we show that cardiomyocyte specific over-expression of the nuclear-matrix associated DNA replication protein, CIZ1, extends their window of proliferation during cardiac development, delaying onset of terminal differentiation without compromising function. CIZ1 expressing hearts are enlarged, but the cardiomyocytes are smaller with an overall increase in number, correlating with increased DNA replication after birth and retention of an increased proportion of mono-nucleated cardiomyocytes into adulthood. Furthermore, these CIZ1 induced changes in the heart reduce the impact of myocardial injury, identifying CIZ1 as a putative therapeutic target for cardiac repair
Chicken muscle mitochondrial content appears coordinately regulated and is associated with performance phenotypes
Authors: Reverter Antonio , Okimoto Ron , Sapp Robyn , Bottje Walter G. , Hawken Rachel , Hudson Nicholas J.
Published: December 2016

Mitochondrial content is a fundamental cellular bioenergetic phenotype. Previous work has hypothesised possible links between variation in muscle mitochondrial content and animal performance. However, no population screens have been performed in any production species. Here, we have designed a high throughput molecular approach to estimate mitochondrial content in commercial broilers. Technical validity was established using several approaches including its performance in monoclonal DF-1 cells, cross-tissue comparisons in tissues with differing metabolic demands (white fat<breast muscle<drumstick muscle<heart muscle) and, as a negative control, a near absence of mtDNA amplification from whole blood. We screened breast muscle and thigh muscle in 80 birds individually phenotyped for 11 growth and development traits. Substantial individual variation (5-fold) was discovered in both breast and thigh muscle mitochondrial content. Interestingly, across birds we detected a very strong positive relationship between breast and thigh content (correlation coefficient 0.61; P<0.0001), consistent with coordinate regulatory control across the musculature. Further, breast muscle mitochondrial content is negatively correlated with breast muscle yield (−0.27; P=0.037), abdominal fat content (−0.31; P=0.017) and carcass yield (−0.26; P=0.045). Therefore, low breast muscle mitochondrial content is associated with more muscular birds possessing higher abdominal fat, the latter being in line with biomedical models of obesity. Finally, thigh mitochondrial content is negatively correlated with the bow out leg defect (−0.30; P=0.011). Overall, our data point to mitochondrial content as a promising consideration in predictive modelling of production traits.
The developmental transcriptome of contrasting Arctic charr (Salvelinus alpinus) morphs
Authors: Gudbrandsson Johannes , Ahi Ehsan P. , Franzdottir Sigridur R. , Kapralova Kalina H. , Kristjansson Bjarni K. , Steinhaeuser S. Sophie , Maier Valerie H. , Johannesson Isak M. , Snorrason Sigurdur S. , Jonsson Zophonias O. , Palsson Arnar
Published: December 2016

Species and populations with parallel evolution of specific traits can help illuminate how predictable adaptations and divergence are at the molecular and developmental level. Following the last glacial period, dwarfism and specialized bottom feeding morphology evolved rapidly in several landlocked Arctic charrSalvelinus alpinuspopulations in Iceland.  

To study the genetic divergence between small benthic morphs and limnetic morphs, we conducted RNA-sequencing charr embryos at four stages in early development. We studied two stocks with contrasting morphologies: the small benthic (SB) charr from Lake Thingvallavatn and Holar aquaculture (AC) charr.

The data reveal significant differences in expression of several biological pathways during charr development. There was also an expression difference between SB- and AC-charr in genes involved in energy metabolism and blood coagulation genes. We confirmed differing expression of five genes in whole embryos with qPCR, includinglysozymeandnatterin-likewhich was previously identified as a fish-toxin of a lectin family that may be a putative immunopeptide. We also verified differential expression of 7 genes in the developing head that associated consistently with benthic v.s.limnetic morphology (studied in 4 morphs). Comparison of single nucleotide polymorphism (SNP) frequencies reveals extensive genetic differentiation between the SB and AC-charr (~1300 with more than 50% frequency difference). Curiously, three derived alleles in the otherwise conserved 12s and 16s mitochondrial ribosomal RNA genes are found in benthic charr.

The data implicate multiple genes and molecular pathways in divergence of small benthic charr and/or the response of aquaculture charr to domestication. Functional, genetic and population genetic studies on more freshwater and anadromous populations are needed to confirm the specific loci and mutations relating to specific ecological traits in Arctic charr.
Identification of genetic pathways driving Ebola virus disease in humans and targets for therapeutic intervention
Authors: Achinko Daniel A. , Dormer Anton , Narayanan Mahesh , Norman Elton F. , Abbas Muneer
Published: December 2016

Introduction: LCKgene, also known as lymphocyte-specific proto-oncogene, is expressed in lymphocytes, and associated with coordinated expression of MHC class I and II in response to physiological stimuli, mediated through a combined interaction of promoters, suppressors, and enhancers. Differential usage ofLCKpromoters, transcribes dysfunctional transcript variants leading to leukemogenesis and non-induction of MHC class I gene variants. Viruses use C-type lectins, likeCD209,to penetrate the cell, and inhibit Pattern Recognition Receptors (PRR), hence evading immune destruction. Given that Ebolavirus (EBOV) disease burden could result from a dysfunctional LCK pathway, identification of the genetic pathway leading to proper immune induction is a major priority.Methods:Data for EBOV related virus samples were obtained from Gene Expression Omnibus database and RMEAN information per gene per sample were entered into a table of values. R software v.3.3.1 was used to process differential expression patterns across samples forLCK, CD209and immune-related genes. Principal component analysis (PCA) using ggbiplot v.0.55 was used to explain the variance across samples.Results:Data analyses identified three viral clusters based on transmission patterns as follows:LCK-CD209dependent, LCK-dependent specific to EBOV, and CD209 dependent. Compared to HLA class II gene variants, HLA class I (A, B and C) variants were <2 fold expressed, especially for EBOV samples. PCA analyses classifiedTYRO3,TBK1andLCKgenes independent of the data, leading to identification of a possible pathway involvingLCK, IL2, PI3k, TBK1, TYRO3andMYBgenes with downstream induction of immune T-cells.Discussion: This is the first study undertaken to understand the non-functional immune pathway, leading to EBOV disease pathogenesis and high fatality rates. Our lab currently exploits, through cutting edge genetic technology to understand the interplay of identified genes required for proper immune induction. This will guide antiviral therapy and possible markers for viral disease identification during outbreaks.
Low-cost, rapidly-developed, 3D printed in vitro corpus callosum model for mucopolysaccharidosis type I
Authors: Tabet Anthony , Gardner Matthew , Swanson Sebastian , Crump Sydney , McMeekin Austin , Gong Diana , Tabet Rebecca , Hacker Benjamin , Nestrasil Igor
Published: December 2016

The rising prevalence of high throughput screening and the general inability of (1) two dimensional (2D) cell culture and (2)in vitrorelease studies to predictin vivoneurobiological and pharmacokinetic responses in humans has led to greater interest in more realistic three dimensional (3D) benchtop platforms. Advantages of 3D human cell culture over its 2D analogue, or even animal models, include taking the effects of microgeometry and long-range topological features into consideration. In the era of personalized medicine, it has become increasingly valuable to screen candidate molecules and synergistic therapeutics at a patient-specific level, in particular for diseases that manifest in highly variable ways. The lack of established standards and the relatively arbitrary choice of probing conditions has limitedin vitrodrug release to a largely qualitative assessment as opposed to a predictive, quantitative measure of pharmacokinetics and pharmacodynamics in tissue. Here we report the methods used in the rapid, low-cost development of a 3D model of a mucopolysaccharidosis type I patient’s corpus callosum, which may be used for cell culture and drug release. The CAD model is developed fromin vivobrain MRI tracing of the corpus callosum using open-source software, printed with poly (lactic-acid) on a Makerbot Replicator 5X, UV-sterilized, and coated with poly (lysine) for cellular adhesion. Adaptations of material and 3D printer for expanded applications are also discussed.
Lotman and play: For a theory of playfulness based on semiotics of culture
Authors: Thibault Mattia
Published: December 2016

The aim of the article is to introduce an approach to play based on semiotics of culture and, in particular, grounded in the works and ideas of Juri Lotman. On the one hand, it provides an overview of Lotman’s works dedicated to play and games, starting from his article on art among other modelling systems, in which the phenomenon of play is treated deeply, and mentioning Lotman’s articles dedicated to various forms of play forms, such as involving dolls and playing cards. On the other hand, it applies a few Lotmanian theories and ideas to playfulness in order to shed some light on this highly debated, as well as intriguing, anthropic activity. Thus, the paper approaches some of the core questions for a play theory, such as the definition of play, the cultural role of toys and playthings, the importance of unpredictability, the position held by playfulness in the semiosphere and, finally, the differences and commonalities between play and art. Lotman’s theories and works, often integrated by other existing semiotic or ludologic perspectives offer an extremely insightful and fresh take on play and illustrate the great heuristic potential of semiotics of culture.