bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Review of the Utility of Postoperative Imaging in the Management of Pediatric Supracondylar Humerus Fractures
Authors: Zusman Natalie L. , Barney Nicole A. , Woelber Erik , Yang Scott
Published: August 2019

Background:

Recently published studies call into question the clinical utility of postoperative radiographs in the management of pediatric supracondylar humerus (SCH) fractures. This topic has been addressed as part of the American Academy of Orthopaedic Surgeons Appropriate Use Criteria, although recommendations regarding serial radiographs were not included as part of the discussion. The purpose of this systematic review is to summarize the recent literature regarding the utility of postoperative radiographs as part of the management of SCH fractures.

Methods:

A systematic review of the literature published between January 1, 2000 and December 31, 2017 was conducted using PubMed/MEDLINE and SCOPUS databases to identify studies relevant to postoperative management of SCH. Eight studies met the inclusion criteria, from which data pooled estimates and an analysis of heterogeneity were calculated.

Results:

The pooled estimate of changes in fracture management on the basis of postoperative radiographs was 1% (0.98±0.33). Significant interstudy heterogeneity was observed with an I
2 test statistic of 76%. Changes in fracture management included prolonged immobilization following pin removal and return to the operating room.

Conclusions:

There is a paucity of articles focusing on the utility or appropriate use of postoperative radiographs in changing management of SCH fractures, one of the most common upper extremity fractures in children. There is a very low rate of change in management on the basis of imaging, and frequently authors commented that the management change could have been prompted without routine serial radiographs. The cumulate findings of these studies suggest routine postoperative radiographs after SCH fractures are infrequently associated with changes in management. Practitioners should consider postoperative protocols with the intention of identifying early postoperative alignment loss or when the complication is suspected to prevent excessive routine radiography in the management of pediatric SCH fractures.

Level of Evidence:

Level III—systematic review of level III studies.
U.K. Intensivists’ Preferences for Patient Admission to ICU: Evidence From a Choice Experiment
Authors: Bassford Christopher R. , Krucien Nicolas , Ryan Mandy , Griffiths Frances E. , Svantesson Mia , Fritz Zoe , Perkins Gavin D. , Quinton Sarah , Slowther Anne-Marie
Published: August 2019

Objectives:

Deciding whether to admit a patient to the ICU requires considering several clinical and nonclinical factors. Studies have investigated factors associated with the decision but have not explored the relative importance of different factors, nor the interaction between factors on decision-making. We examined how ICU consultants prioritize specific factors when deciding whether to admit a patient to ICU.

Design:

Informed by a literature review and data from observation and interviews with ICU clinicians, we designed a choice experiment. Senior intensive care doctors (consultants) were presented with pairs of patient profiles and asked to prioritize one of the patients in each task for admission to ICU. A multinomial logit and a latent class logit model was used for the data analyses.

Setting:

Online survey across U.K. intensive care.

Subjects:

Intensive care consultants working in NHS hospitals.

Measurements and Main Results:

Of the factors investigated, patient’s age had the largest impact at admission followed by the views of their family, and severity of their main comorbidity. Physiologic measures indicating severity of illness had less impact than the gestalt assessment by the ICU registrar. We identified four distinct decision-making patterns, defined by the relative importance given to different factors.

Conclusions:

ICU consultants vary in the importance they give to different factors in deciding who to prioritize for ICU admission. Transparency regarding which factors have been considered in the decision-making process could reduce variability and potential inequity for patients.
Randomized Clinical Trial of an ICU Recovery Pilot Program for Survivors of Critical Illness*
Authors: Bloom Sarah L. , Stollings Joanna L. , Kirkpatrick Olivia , Wang Li , Byrne Daniel W. , Sevin Carla M. , Semler Matthew W.
Published: August 2019

Objectives:

To examine the effect of an interdisciplinary ICU recovery program on process measures and clinical outcomes.

Design:

A prospective, single-center, randomized pilot trial.

Setting:

Academic, tertiary-care medical center.

Patients:

Adult patients admitted to the medical ICU for at least 48 hours with a predicted risk of 30-day same-hospital readmission of at least 15%.

Interventions:

Patients randomized to the ICU recovery program group were offered a structured 10-intervention program, including an inpatient visit by a nurse practitioner, an informational pamphlet, a 24 hours a day, 7 days a week phone number for the recovery team, and an outpatient ICU recovery clinic visit with a critical care physician, nurse practitioner, pharmacist, psychologist, and case manager. For patients randomized to the usual care group, all aspects of care were determined by treating clinicians.

Measurements and Main Results:

Among the primary analysis of enrolled patients who survived to hospital discharge, patients randomized to the ICU recovery program (n = 111) and usual care (n = 121) were similar at baseline. Patients in the ICU recovery program group received a median of two interventions compared with one intervention in the usual care group (p < 0.001). A total of 16 patients (14.4%) in the ICU recovery program group and 26 patients (21.5%) in the usual care group were readmitted to the study hospital within 30 days of discharge (p = 0.16). For these patients, the median time to readmission was 21.5 days (interquartile range, 11.5–26.2 d) in the ICU recovery program group and 7 days (interquartile range, 4–21.2 d) in the usual care group (p = 0.03). Four patients (3.6%) in the ICU recovery program and 14 patients (11.6%) in the usual care group were readmitted within 7 days of hospital discharge (p = 0.02). The composite outcome of death or readmission within 30 days of hospital discharge occurred in 20 patients (18%) in the ICU recovery program group and 36 patients (29.8%) in usual care group (p = 0.04).

Conclusions:

This randomized pilot trial found that a multidisciplinary ICU recovery program could deliver more interventions for post ICU recovery than usual care. The finding of longer time-to-readmission with an ICU recovery program should be examined in future trials.
Persistent Mitochondrial Dysfunction Linked to Prolonged Organ Dysfunction in Pediatric Sepsis
Authors: Weiss Scott L. , Zhang Donglan , Bush Jenny , Graham Kathryn , Starr Jonathan , Tuluc Florin , Henrickson Sarah , Kilbaugh Todd , Deutschman Clifford S. , Murdock Deborah , McGowan Francis X. , Becker Lance , Wallace Douglas C.
Published: August 2019

Objectives:

Limited data exist about the timing and significance of mitochondrial alterations in children with sepsis. We therefore sought to determine if alterations in mitochondrial respiration and content within circulating peripheral blood mononuclear cells were associated with organ dysfunction in pediatric sepsis.

Design:

Prospective observational study

Setting:

Single academic PICU.

Patients:

One-hundred sixty-seven children with sepsis/septic shock and 19 PICU controls without sepsis, infection, or organ dysfunction.

Interventions:

None.

Measurements and Main Results:

Mitochondrial respiration and content were measured in peripheral blood mononuclear cells on days 1–2, 3–5, and 8–14 after sepsis recognition or once for controls. Severity and duration of organ dysfunction were determined using the Pediatric Logistic Organ Dysfunction score and organ failure-free days through day 28. Day 1–2 maximal uncoupled respiration (9.7 ± 7.7 vs 13.7 ± 4.1 pmol O2/s/106 cells; p = 0.02) and spare respiratory capacity (an index of bioenergetic reserve: 6.2 ± 4.3 vs 9.6 ± 3.1; p = 0.005) were lower in sepsis than controls. Mitochondrial content, measured by mitochondrial DNA/nuclear DNA, was higher in sepsis on day 1–2 than controls (p = 0.04) and increased in sepsis patients who had improving spare respiratory capacity over time (p = 0.005). Mitochondrial respiration and content were not associated with day 1–2 Pediatric Logistic Organ Dysfunction score, but low spare respiratory capacity was associated with higher Pediatric Logistic Organ Dysfunction score on day 3–5. Persistently low spare respiratory capacity was predictive of residual organ dysfunction on day 14 (area under the receiver operating characteristic, 0.72; 95% CI, 0.61–0.84) and trended toward fewer organ failure-free days although day 28 (β coefficient, –0.64; 95% CI, –1.35 to 0.06; p = 0.08).

Conclusions:

Mitochondrial respiration was acutely decreased in peripheral blood mononuclear cells in pediatric sepsis despite an increase in mitochondrial content. Over time, a rise in mitochondrial DNA tracked with improved respiration. Although initial mitochondrial alterations in peripheral blood mononuclear cells were unrelated to organ dysfunction, persistently low respiration was associated with slower recovery from organ dysfunction.
Clonazepam: Indications, Side Effects, and Potential for Nonmedical Use
Authors: Dokkedal-Silva Vinícius , Berro Laís Fernanda , Galduróz José Carlos Fernandes , Tufik Sergio , Andersen Monica Levy
Published: August 2019

Learning objectives

After participating in this activity, learners should be better able to:

• Assess the misuse potential of clonazepam

• Characterize the nonmedical use of clonazepam

• Identify the health problems associated with long-term use of clonazepam

Clonazepam, a benzodiazepine, is commonly used in treating various conditions, including anxiety disorders and epileptic seizures. Due to its low price and easy availability, however, it has become a commonly misused medication, both in medical and recreational contexts. In this review, we aim to highlight the behavioral and pharmacological aspects of clonazepam and its history following its approval for human use. We examine the circumstances commonly associated with the nonmedical use of clonazepam and raise points of particular concern. Clonazepam, alone or in combination with other psychoactive substances, can lead to unwanted effects on health, such as motor and cognitive impairment, sleep disorders, and aggravation of mood and anxiety disorders. Prolonged use of clonazepam may lead to physical dependence and tolerance. There is therefore a need to find safer therapeutic alternatives for treating seizures and anxiety disorders. Greater awareness of its frequent nonmedical use is also needed to achieve safer overall use of this medication.
Preparedness for Clinical Practice and the Development of Professional Competencies
Authors: Carter Kimberly , Stoehr James D.
Published: August 2019

Purpose

To assess students' level of perceived preparedness for clinical competencies and simultaneously identify the effective curricular methods to develop these competencies.

Methods

Prior to graduation students reported their level of preparedness for clinical practice using a modified Preparation for Hospital Practice Questionnaire and rated the most effective teaching methods to improve the development of clinical and professional competencies.

Results

Students gave a high rating to group dynamics and teamwork, along with continuous professional development. They felt least prepared in pharmacotherapeutics and the handling of medical emergencies. Rated most effective were didactic lecturing instruction for the acquisition of medical knowledge, standardized patient encounters and simulations for the promotion of interpersonal skills, case groups for the integration of knowledge and critical thinking, and interprofessional events for the maintenance of professional accountability.

Conclusion

This survey approach may lead to an efficient and focused method for improving clinical and professional competencies and serve as an additional self-assessment tool to support curriculum development and reform.
Student-Led Mobile Health Clinic: Patients Served and Learning Experience
Authors: Duford Amie , Matvienko Oksana
Published: August 2019

Purpose

Community medicine curriculum prepares physician assistant (PA) students to provide services to vulnerable and underserved populations. This article describes a service-learning model that uses a mobile health clinic (MHC) experience as part of the community medicine rotation. It provides an overview of the clinic's operation, patient documentation and characteristics, and student learning experiences.

Methods

Students collected demographic information on patients who visited the MHC during January through December 2017. The students summarized patient demographics and reflected on their experiences in a report.

Results

Two main outcomes are discussed: characteristics of the MHC patients and student observations about their experiences. In 2017, 113 students rotated through the MHC and recorded 813 patient encounters. The largest proportions of patients reported living on the street or in a shelter (71%) and were older than 56 years (40%), males (74%), Caucasian (43%), single (65%), nonveterans (77%), and high school graduates (41%). The top 5 reasons for visits were preventive care, cognitive/functional impairment, cardiometabolic disorders, skin issues, and respiratory illness. The MHC experience and process of recording and analyzing demographic data contributed to students' data management and analytical skills. The students identified problems of recordkeeping and their implications for patient care, gained a greater understanding of medical needs and complexities of treating the homeless, and provided suggestions for improving quality and efficiency of care.

Conclusions

The MHC service-learning model provides diverse, meaningful experiences for students. Our findings benefit PA programs aiming to expand and strengthen their community medicine curriculum.
Impact of Variations in PACKRAT Administration: A Retrospective Review
Authors: Rizzolo Denise , Cavanagh Kim , Ziegler Olivia , Janal Malvin
Published: August 2019

The Physician Assistant Clinical Knowledge Rating and Assessment Tool (PACKRAT) was developed to be an objective, comprehensive self-assessment tool for students. When the PACKRAT exam was initially developed, its goal was to help students determine what level of knowledge they currently possessed and what they had to learn prior to graduation. The purpose of this study was to review PACKRAT test-taker scores over the past 5 years and analyze the variations in test administration. Deidentified PACKRAT scores, exam length in minutes, and proctored or unproctored status, along with time extensions were analyzed from 2013 to 2018. Descriptive statistics and frequency counts were used to summarize the data. An independent samples t-test was used to determine if there was a difference in test-taker scores between proctored and unproctored exams. The 83,271 student test-taker exam data were analyzed, and time ranged from 180 to 360 minutes with a mean of 226.5 minutes. When comparing test-taker scores between proctored and unproctored exams, the mean scores were 145.02 and 144.77, respectively, with no significant difference. The Physician Assistant Clinical Knowledge Rating and Assessment Tool can be confidently used and compared to national scores whether a program administers the exam proctored or without a proctor. The average time taken for exam completion is close to the recommended 225 minutes that is suggested by Physician Assistant Education Association PACKRAT exam developers.
Evaluation of a nurse practitioner–led transitional care program
Authors: Sherlock Patrick J. , Rounds Linda R.
Published: August 2019

Background:

Transitional care management (TCM) is a growing field in the delivery of post hospital discharge care. Current data suggest that implemented nurse practitioner (NP)-led transitional care models can be useful in reducing 30-day readmission rates. However, there is lack of data regarding the costs involved to implement and sustain a transitional care model.

Local problem:

The Transitional Care Encounter Program (TCEP) implemented by an NP at a private practice affiliated with a 250-bed acute care facility required program evaluation. This article addresses the TCEP's cost and sustainability, reimbursement, and nonmonetary value added to the practice.

Methods:

The Centers for Disease Control and Prevention (1999) “Framework for Program Evaluation in Public Health” was used for formal program evaluation. The TCEP's billing and revenue data compared with the TCEP's cost determined the financial impact. Qualitative data were also collected.

Interventions:

Patients discharged from the hospital to home had a TCEP visit within 7 days of discharge. The patient's hospital records were extensively reviewed. Medication reconciliation, education about current medications, diagnosis, and treatment plan were incorporated.

Results:

Total reimbursement was $53,330.32. Providers expressed they could allocate more time to primary care patients and averaged 2–3 more patients by having a dedicated transitional care provider. Providers expressed patients were “empowered” after the TCEP visit.

Conclusions:

The TCEP was a source of revenue and improved provider satisfaction. Exploration of the TCM's impact on 30-day readmission rates and patient satisfaction are recommended to further support the model.
Hyperimmunoglobulinemia and IgG Subclass Abnormalities in Children With Gaucher Disease
Authors: Marzouk Iman , Deghady Akram , Omar Omneya M. , Ashour Rofaida S.
Published: August 2019

Gaucher disease (GD) is the most common lysosomal storage disorder, the aim of the current study was to investigate hyperimmunoglobulinemia and abnormalities of serum immunoglobulin G (IgG) subclasses in children with GD and the relation of those findings to the GD phenotype and genotype, duration of enzyme replacement therapy (ERT), and infection frequency. The study included 20 Egyptian children with GD receiving ERT and 20 age-matched and sex-matched healthy children as controls. Serum Ig and serum IgG subclass levels were measured in the children with GD. Serum IgG subclass levels were measured in the control subjects. Hyperimmunoglobulinemia was present in 15 of the 20 (75%) children with GD. In addition, it is found significantly lower IgG2 levels and significantly higher IgG3 levels in the GD group than in the control group (P<0.001 and <0.006, respectively). Patients with 12 infections per year had significantly higher IgG3 levels compared with patients with 6 infections per year (P=0.022). In conclusion, hyperimmunoglobulinemia and IgG subclass abnormalities occur in children with GD who are on ERT and may be related to recurrent infections.
How Does Comprehensive Care Impact Life of Pediatric Patients With Hemophilia? Results From a Center in a Developing Country
Authors: Villarreal-Martínez Laura , Meléndez-Aguirre Atenas , Cantú-Moreno Marcela , Garay-Mendoza Domingo , Garza José A. , Ibarra-Ramírez Marisol , Quiroga-Treviño Marbely , Pope-Salazar Sulia E. , Velasco-Ruiz Ileana
Published: August 2019

Background:

Quality of life (QoL) has been included as a marker of treatment effectiveness in pediatric patients with chronic diseases. We believe that frequent multidisciplinary interventions and patient education could lead to an improvement in QoL.

Aims:

Determine the QoL and economic impact of monthly interventions in multidisciplinary treatment.

Materials and Methods:

The Haemo-QoL questionnaire was applied to patients who attended the hemophilia center of the University Hospital “Dr. José Eleuterio González,” Monterrey, Mexico, at the time of enrollment and 1 year later.

Results:

Male patients between 4 and 16 years diagnosed with hemophilia were included. The score results presented are based on Haemo-QoL versions that classify patients by their age group: group 1 (4 to 7 y) and group 2 (8 to 12 y). Statistical significant improvement was observed in the overall score (sociodemographic, psychosocial, etc.) after 1 year of follow-up in both groups (P<0.05).

Conclusions:

Impact on the QoL of patients receiving this approach was favorable. Improvement was observed regardless of severity and in those who were already in prophylaxis, suggesting that this type of approach could be causing the improvement. Results support the application of multidisciplinary treatment as the gold standard, and it should be considered in all centers including those with limited resources.
Sedentary behaviour facilitates conditioned pain modulation in middle-aged and older adults with persistent musculoskeletal pain: a cross-sectional investigation
Authors: Mani Ramakrishnan , Adhia Divya Bharatkumar , Leong Sook Ling , Vanneste Sven , De Ridder Dirk
Published: August 2019

Introduction:

Higher physical activity (PA) and lower sedentary behaviour (SB) levels have demonstrated beneficial effects on temporal summation (TS) and conditioned pain modulation (CPM) in healthy adults. This cross-sectional study investigated the relationships between PA and SB and TS/CPM responses in individuals with chronic musculoskeletal pain.

Methods:

Sixty-seven middle-aged and older adults with chronic musculoskeletal pain were recruited from the community. Questionnaires measuring demographics, pain, and psychological measures were completed. Physical activity/SB levels were measured using the International Physical Activity Questionnaire—short form and Sedentary Behaviour Questionnaire, respectively. Semmes monofilament was used to assess mechanical TS (MTS) at the most symptomatic (MTS-S) and a reference region (MTS-R); change in the pain scores (baseline-10th application) was used for analysis. Conditioned pain modulation procedure involved suprathreshold pressure pain threshold (PPT-pain4) administered before and after (CPM30sec, CPM60sec, and CPM90sec) conditioning stimulus (2 minutes; ∼12°C cold bath immersion). For analysis, PPT-pain4 (%) change scores were used.

Results:

PPT-pain4 (%) change scores at CPM30sec and CPM60sec demonstrated significant weak positive correlations with SB levels and weak negative correlations with PA measures. After adjusting for confounding variables, a significant positive association was found between SB (h/d) and PPT-pain4 (%) change scores at CPM30sec and CPM60sec. No significant associations between MTS and PA/SB measures.

Conclusion:

Sedentariness is associated with higher pain inhibitory capacity in people with chronic musculoskeletal pain. The observed relationship may be characteristic of a protective (sedentary) behaviour to enhance pain modulatory mechanism. Prospective longitudinal studies using objective PA/SB measures are required to validate the observed relationship in a larger sample size.
Consolidation Time and Relapse: A Systematic Review of Outcomes in Internal versus External Midface Distraction for Syndromic Craniosynostosis
Authors: Bertrand Anthony A. , Lipman Kelsey J. , Bradley James P. , Reidhead Jacob , Lee Justine C.
Published: August 2019

Background:

The choice between internal and external distraction osteogenesis for midface advancement in patients with syndromic craniosynostosis is based primarily on surgeon preference and expertise. However, differences in outcomes between the two techniques have been sparingly compared. In this work, the authors performed a systematic review to compare outcomes between internal versus external midface distraction.

Methods:

A systematic review was performed of studies published between 1998 and 2018 (61 studies included; n = 689 patients). Operative characteristics, early reoperations, complications, and relapse rates were extracted. Bias evaluation was performed using the Newcastle-Ottawa instrument. Statistical analyses were performed with independent samples t tests and linear regression analyses (p < 0.05 considered significant).

Results:

The authors found that external distraction was associated with more Le Fort III osteotomies and hardware adjustments (p = 0.023), whereas internal distraction was associated with more monobloc osteotomies and longer consolidation times (p = 0.008). No significant differences in the distance of midface advancement, reoperations, complications, or relapse rates were noted between internal versus external distraction, although external distraction trended toward a slightly higher relapse rate. Regardless of distraction protocol, consolidation time was found to be a strong negative predictor for relapse (beta = −0.792; p = 0.02).

Conclusions:

No significant differences were demonstrated in advancement distance, reoperative rates, complication rates, or relapse rates for internal versus external distraction for midface advancement. Regardless of distraction type, consolidation time was strongly inversely associated with relapse rates. The trend toward higher relapse in external distraction is potentially explained by the significantly lower consolidation times.
Angiotensin II Type I Receptor Blockade Is Associated with Decreased Cutaneous Scar Formation in a Rat Model
Authors: Murphy Amanda , LeVatte Terry , Boudreau Colton , Midgen Craig , Gratzer Paul , Marshall Jean , Bezuhly Michael
Published: August 2019

Background:

Angiotensin II engagement of angiotensin II type 1 receptor (AT1R) is implicated in fibrogenesis, with AT1R blockers used clinically to attenuate cardiac and renal fibrosis. The authors tested the hypothesis that the AT1R blocker losartan could reduce postsurgical cutaneous scarring in rats.

Methods:

Human dermal fibroblasts were treated with losartan and assessed for viability, contractile activity, migration, and profibrotic gene transcription by means of calcein, collagen gel, scratch, and quantitative reverse transcriptase polymerase chain reaction assays, respectively. Monocyte migration and adhesion to losartan-treated and control fibroblasts were examined. Losartan effects in vivo were assessed using a mechanical distraction hypertrophic scar model. Three days after incisions were made and closed on their backs, rats were assigned randomly to receive drinking water with or without losartan (1 mg/kg per day; n = 6 per group). Distraction devices were applied and activated up to day 14. On day 28, scars underwent cross-sectional area and elevation index analyses, and α-SMA+ (alpha-smooth muscle actin) and CD68+ (monocyte/macrophage marker) immunostaining.

Results:

Losartan-treated human dermal fibroblasts displayed decreased contractile activity, migration, and gene expression of transforming growth factor-β1, collagen I, and monocyte chemoattractant protein-1 relative to controls (p < 0.05). Monocyte migration and adhesion to losartan-treated fibroblasts were reduced (p < 0.01). Compared to controls, scars from losartan-treated rats demonstrated decreased cross-sectional area (19.4 ± 3.1 mm2 versus 45.0 ± 5.2 mm2; p = 0.002), elevation index (1.5 ± 0.1 versus 2.6 ± 0.3; p = 0.003), and α-SMA+ and CD68+ immunostaining (p < 0.001).

Conclusions:

Losartan decreases myofibroblast activity and reduces monocyte trafficking to cutaneous scar. These findings support losartan as a potential novel therapy for the prevention of hypertrophic scars.
Exosomes Are Comparable to Source Adipose Stem Cells in Fat Graft Retention with Up-Regulating Early Inflammation and Angiogenesis
Authors: Chen Bin , Cai Junrong , Wei Yating , Jiang Zhaohua , Desjardins Haley E. , Adams Alexandra E. , Li Shengli , Kao Huang-Kai , Guo Lifei
Published: August 2019

Background:

Exosomes derived from mesenchymal stem cells possess functional properties similar to those of their parent cells, suggesting that they could play a pivotal role in tissue repair and regeneration.

Methods:

Using lipotransfer as a surrogate, exosomes were isolated from mouse adipose-derived stem cell–conditioned medium and characterized. Minced fat tissue mixed with exosomes, source cells (cell-assisted lipotransfer), or saline was implanted subcutaneously in the lower back of C57/BL mice bilaterally (n= 16 each). Transferred fat tissues were harvested and analyzed at 3 and 10 weeks.

Results:

At 3 and 10 weeks after the transfer, fat grafts in groups of exosomes and cell-assisted lipotransfer showed better fat integrity, fewer oil cysts, and reduced fibrosis. At week 10, graft retention rates in cell-assisted lipotransfer (50.9 ± 2.4 percent;p= 0.03) and exosome groups (56.4 ± 1.6 percent;p< 0.001) were significantly higher than in the saline group (40.7 ± 4.7 percent). Further investigations of macrophage infiltration, inflammatory factors, angiogenic factors, adipogenic factors, and extracellular matrix revealed that those exosomes promoted angiogenesis and up-regulated early inflammation, whereas during mid to late stages of fat grafting, they exerted a proadipogenic effect and also increased collagen synthesis level similarly to their source cells.

Conclusions:

The adipose-derived stem cell–derived exosomes demonstrated effects comparable to those of their source cells in achieving improved graft retention by up-regulating early inflammation and augmenting angiogenesis. These features may enable exosomes to be an attractive cell-free alternative in therapeutic regenerative medicine.
Stress-Induced Suppression of Food Intake in Overweight and Obese Adolescents
Authors: Nagy Matthew R. , Gill Amaanat , Adams Tessa , Gerras Julia , Mazin Lauren , Leung Cindy , Hasson Rebecca E.
Published: August 2019

Objective

Overweight adolescents exhibit greater cortisol reactivity in response to acute stress and are more likely to eat in response to emotional cues, which suggest an increased susceptibility to stress-induced eating. The purpose of this study was to examine the biological (cortisol and α-amylase reactivity) and behavioral (caloric intake) responses to an acute stressor in overweight adolescents.

Methods

Fifty-one adolescents ages 14 to 19 years (47% female, 55% white; body mass index, 31.2 ± 0.8 kg/m2) were exposed to the Trier Social Stress Test and a control condition on separate days. Immediately after each condition, participants were provided with snacks to eat at their leisure. Reactivity was assessed via salivary cortisol and α-amylase area under the curve (AUC), and adolescents were categorized as high or low reactors.

Results

Cortisol AUC was higher during the stress condition (19.6 ± 0.2 μg/dl · min) compared with the control condition (11.4 ± 0.9 μg/dl · min,p< .001). α-Amylase AUC was not different during the stress condition (9999 ± 987 U/ml · min) compared with the control condition (8762 ± 865 U/ml · min,p= .145). Overall, adolescents consumed fewer calories during the stress condition (488 ± 51 kcal) compared with the control condition (637 ± 42 kcal,p= .007). High cortisol reactors decreased their calorie consumption from the control condition (716 ± 52 kcal) to the stress condition (457 ± 53 kcal,p= .001), whereas low cortisol reactors did not change their consumption (stress: 518 ± 87 kcal versus control: 561 ± 62 kcal,p= .574).

Conclusion

High cortisol reactivity in overweight adolescents resulted in decreased calorie consumption after an acute stressor. Further research is needed to understand the mechanisms underlying stress-induced suppression of food intake in overweight adolescents.
Posttransplant Lymphoproliferative Disorder in Pediatric Patients: Characteristics of Disease in EBV-seropositive Recipients
Authors: L’Huillier Arnaud G. , Dipchand Anne I. , Ng Vicky L. , Hebert Diane , Avitzur Yaron , Solomon Melinda , Ngan Bo-Yee , Yeung Simon , Stephens Derek , Punnett Angela S. , Barton Michelle , Allen Upton D.
Published: August 2019

Background.

Patients at greatest risk of posttransplant lymphoproliferative disorder (PTLD) are those who acquire primary Epstein-Barr virus (EBV) infection after solid organ transplantation. The incidence of PTLD among patients who are EBV-seropositive before transplant is lower, and little is known about the differences in presentation and outcome of this population. We describe the characteristics of EBV-seropositive transplant recipients (R+) who developed PTLD and compare survival outcomes with EBV-seronegative recipients (R−).

Methods.

A hospital-based registry was used to identify all patients with biopsy-proven PTLD for the period 2000–2014. Characteristics and outcomes were compared between R+ and R− patients with PTLD.

Results.

Sixty-nine patients were included, among which 20 (29.0%) were R+ and 49 (71.0%) were R−. Multiorgan transplant patients accounted for 25% of PTLD cases in R+ patients, while accounting for only 2.1% of all transplants during the study period. There was no difference in PTLD site between R+ and R− patients. PTLD among R+ individuals occurred during the second year after transplant (median: 1.92; range: 0.35–3.09 y) compared with during the first year for R− individuals (median: 0.95; range: 0.48–2.92 y; P = 0.380). There was a trend for a higher overall mortality among R+ individuals (log rank: 0.09). PTLD-related mortality did not differ between R+ and R− individuals (log rank: 0.17).

Conclusions.

PTLD among R+ individuals was more likely to occur among multiorgan recipients, and there was a tendency for poorer outcomes at 1 and 5 years after the diagnosis of PTLD.
The smallest proton-bound dimer H
5
+
: theoretical progress
Authors: Prosmiti Rita , Valdés Álvaro
Published: August 2019

The protonated hydrogen dimer, H
5
+
, is the smallest system including proton transfer, and has been of long-standing interest since its first laboratory observation in 1962. H
5
+
and its isotopologues are the intermediate complexes in deuterium fractionation reactions, and are of central importance in molecular astrophysics. The recently recorded infrared spectra of both H
5
+
and D
5
+
reveal a rich vibrational dynamics of the cations, which presents a challenge for standard theoretical approaches. Although H
5
+
is a four-electron ion, which makes highly accurate electronic structure calculations tractable, the construction of
ab initio
-based potential energy and dipole moment surfaces has proved a hard task. In the same vein, the difficulties in treating the nuclear motion could also become cumbersome due to their high dimensionality, floppiness and/or symmetry. These systems are prototypical examples for studying large-amplitude motions, as they are highly delocalized, interconverting between equivalent minima through internal rotation and proton transfer motions requiring state-of-the-art treatments. Recent advances in the computational vibrational spectroscopy of the H
5
+
cation and its isotopologues are reported from full quantum spectral simulations, providing important information in a rigorous manner, and open perspectives for further future investigations.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.
Dissociative recombination of H3+and D5+
Authors: Larsson Mats
Published: August 2019

Compared with earlier years, the dissociative recombination ofH3+has not been very actively studied in recent years. New results from afterglow experiments are quoted and compared with results from ion storage rings and theory. New results forD5+are discussed. This article also contains some historical remarks on hydrogen and its importance for the advancement of physics and chemistry.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H3+, H5+and beyond’.
General mathematical formulation of scattering processes in atom–diatomic collisions in the RmatReact methodology
Authors: McKemmish Laura K. , Tennyson Jonathan
Published: August 2019

Accurately modelling cold and ultracold reactive collisions occurring over deep potential wells, such as

D

+

+

H

2

→

H

+

+

HD

, requires the development of new theoretical and computational methodologies. One potentially useful framework is the
R
-matrix method adopted widely for electron–molecule collisions which has more recently been applied to non-reactive heavy-particle collisions such as Ar–Ar. The existing treatment of non-reactive elastic and inelastic scattering needs to be substantially extended to enable modelling of reactive collisions: this is the subject of this paper. Herein, we develop the general mathematical formulation for non-reactive elastic and inelastic scattering, photoassociation, photodissociation, charge exchange and reactive scattering using the
R
-matrix method. Of particular note is that the inner region, of central importance to calculable
R
-matrix methodologies, must be finite in all scattering coordinates rather than a single scattering coordinate as for non-reactive scattering.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.
Astrochemical studies at the Cryogenic Storage Ring
Authors: Kreckel H. , Novotný O. , Wolf A.
Published: August 2019

The new Cryogenic Storage Ring at the Max Planck Institute for Nuclear Physics (Heidelberg, Germany) has recently become operational. One of the main research areas foreseen for this unique facility is astrochemical studies with cold molecular ions. The spontaneous radiative cooling of the prototype interstellar molecule CH
+
to its lowest rotational states has been demonstrated by photodissociation spectroscopy, paving the way for experiments under true interstellar conditions. To this end, a low-energy electron cooler and a neutral atom beam set-up for merged beams studies have been constructed. These experiments have the potential to provide energy-resolved rate coefficients for fundamental astrochemical processes involving state-selected molecular ions. The main target reactions include some of the key processes of interstellar chemistry, such as the electron recombination of H
3
+
, charge exchange between H
2
+
and H, or the formation of CH
+
in collisions of triatomic hydrogen ions and C atoms.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.
Modelling H
3
+
in planetary atmospheres: effects of vertical gradients on observed quantities
Authors: Moore L. , Melin H. , O'Donoghue J. , Stallard T. S. , Moses J. I. , Galand M. , Miller S. , Schmidt C. A.
Published: August 2019

Since its detection in the aurorae of Jupiter approximately 30 years ago, the H
3
+
ion has served as an invaluable probe of giant planet upper atmospheres. However, the vast majority of monitoring of planetary H
3
+
radiation has followed from observations that rely on deriving parameters from column-integrated paths through the emitting layer. Here, we investigate the effects of density and temperature gradients along such paths on the measured H
3
+
spectrum and its resulting interpretation. In a non-isothermal atmosphere, H
3
+
column densities retrieved from such observations are found to represent a lower limit, reduced by 20% or more from the true atmospheric value. Global simulations of Uranus' ionosphere reveal that measured H
3
+
temperature variations are often attributable to well-understood solar zenith angle effects rather than indications of real atmospheric variability. Finally, based on these insights, a preliminary method of deriving vertical temperature structure is demonstrated at Jupiter using model reproductions of electron density and H
3
+
measurements. The sheer diversity and uncertainty of conditions in planetary atmospheres prohibits this work from providing blanket quantitative correction factors; nonetheless, we illustrate a few simple ways in which the already formidable utility of H
3
+
observations in understanding planetary atmospheres can be enhanced.

This article is part of a discussion meeting issue ‘Advances in hydrogen molecular ions: H
3
+
, H
5
+
and beyond’.
An 11-bit High Dynamic Range (HDR) Luminance Display and Its Use to Discover Contextual Mechanisms of Real-World Luminance Normalization for Visual Acuity and Target Discrimination
Authors: Hung Chou P , Callahan-Flintoft Chloe , Fedele Paul D , Fluitt Kim F , Odoemene Onyekachi , Vaughan Barry D , Walker Anthony J , Jaswa Matthew M , Wei Min , Harrison Andre V
Published: August 2019

Luminance can vary widely when scanning across a scene, by up to 10^9 to 1, requiring multiple normalizing mechanisms spanning from the retina to cortex to support visual acuity and recognition. Vision models based on standard dynamic range luminance contrast ratios below 100 to 1 have limited ability to generalize to real-world scenes with contrast ratios over 10,000 to 1 (high dynamic range [HDR]). Understanding and modeling brain mechanisms of HDR luminance normalization is thus important for military applications, including automatic target recognition, display tone mapping, and camouflage. Yet, computer display of HDR stimuli was until recently unavailable or impractical for research. Here we describe procedures for setup, calibration, and precision check of an HDR display system with over 100,000 to 1 luminance dynamic range (650–0.0065 cd/m^2), pseudo 11-bit grayscale precision, and 3-ms temporal precision in the MATLAB/Psychtoolbox software environment. The setup is synchronized with electroencephalography and IR eye-tracking measurements. We report measures of HDR visual acuity and the discovery of a novel phenomenon—that abrupt darkening (from 400 to 4 cd/m^2) engages contextual facilitation, distorting the perceived orientation of a high-contrast central target. Surprisingly, the facilitation effect depended on luminance similarity, contradicting both classic divisive and subtractive models of contextual normalization.
Physiological and Biochemical Analyses of Sorghum Varieties Reveal Differential Responses to Salinity Stress
Authors: Mbinda W , Kimtai M
Published: August 2019

Salinity is among the most severe and widespread environmental constrains to global crop production, especially in arid and semi-arid climates and negatively affecting productivity of salt sensitive crop species. Breeding and selection of salt tolerant crop varieties is therefore necessary for sustainable plant productivity. Given that germination and seeding phases are the most critical phase in the plant life cycle, this study aimed to evaluate seed germination potential and associated traits under salt stress conditions as a simple approach to identify salt tolerant Sorghum varieties. There Sorghum varieties whose adaptation to various agroclimatic conditions is not well elucidated. Salinity stress was applied by addition of NaCl at three different levels of stress (100, 200 and 300 mM NaCl), while plants irrigated with water were used as controls. Evaluation of tolerance was performed on the basis of germination percentage, shoot and seed water absorbance, shoot and root length, leave water content, seedling total chlorophyll content and morphologic abnormality. Our results showed that salinity stress significantly impacts all features associated with germination and early development of seedlings. Our results indicated that that salinity stress substantially affects all traits associated with germination and early seedling growth, with the effect of salinity being dependent on the variety used and level of salinity stress applied. Among the tested Sorghum varieties, Gadam was established to the most salt tolerant variety, suggesting its potential use for cultivation under salinity stress conditions as well as its suitability for use as germplasm material in future Sorghum breeding programmes. For a greater insight into comprehensive mechanisms of salinity tolerance in Sorghum, we suggest further research on genomic and molecular analysis.
Single Cell Gene Expression Analysis Reveals Human Stem Cell-Derived Graft Composition in a Cell Therapy Model of Parkinson’s Disease
Authors: Tiklová Katarína , Nolbrant Sara , Fiorenzano Alessandro , Björklund Åsa K. , Sharma Yogita , Heuer Andreas , Gillberg Linda , Hoban Deirdre B. , Cardoso Tiago , Adler Andrew F. , Birtele Marcella , Lundén-Miguel Hilda , Volakakis Nikolaos , Kirkeby Agnete , Perlmann Thomas , Parmar Malin
Published: August 2019

Since the pioneering studies using fetal cell transplants in Parkinson’s disease (PD), brain repair by cell replacement has remained a long-standing and realistic goal for the treatment of neurodegenerative disorders including PD. Authentic and functional midbrain dopamine (DA) neurons can now be generated from human pluripotent stem cells (hPSCs) via a floor plate intermediate1,2, and these cell preparations are both safe and functional when transplanted to animal models of PD3. However, although resulting grafts from fetal brain tissue and hPSCs contain large numbers of desired DA neurons, these therapeutic cells are a minor component of the grafts. Moreover, the cellular composition of the graft has remained difficult to assess due to limitations in histological methods that rely on pre-conceived notions concerning cell types. Here, we used single cell RNA sequencing (scRNA-seq) combined with comprehensive histological analyses to characterize intracerebral grafts from ventral midbrain (VM)-patterned human embryonic stem cells (hESCs) and VM fetal tissue after long-term survival and functional maturation in a pre-clinical rat model of PD. The analyses revealed that while both cell preparations gave rise to neurons and astrocytes, oligodendrocytes were only detected in grafts of fetal tissue. On the other hand, a cell type closely resembling a class of newly identified perivascular-like cells was identified as a unique component of hESC-derived grafts. The presence of these cells was confirmed in transplants from three different hESC lines, as well as from iPSCs. Thus, these experiments have addressed one of the major outstanding questions in the field of cell replacement in neurological disease by revealing graft composition and differences between hESC- and fetal cell-derived grafts, which can have important implications for clinical trials.
Peppy: A Virtual Reality Environment for Exploring the Principles of Polypeptide Structure
Authors: Doak David G , Denyer Gareth S , Gerrard Juliet A , Mackay Joel P , Allison Jane R
Published: August 2019

A key learning outcome for undergraduate biochemistry classes is a thorough understanding of the principles of protein structure. Traditional approaches to teaching this material, which include two-dimensional (2D) images on paper, physical molecular modelling kits, and projections of 3D structures into 2D, are unable to fully capture the dynamic, 3D nature of proteins. We have built a virtual reality application, Peppy, aimed at facilitating teaching of the principles of protein secondary structure. Rather than attempt to model molecules with the same fidelity to the underlying physical chemistry as existing, research-oriented molecular modelling approaches, we took the more straightforward approach of harnessing the Unity video game physics engine. Indeed, the simplicity and limitations of our model are a strength in a teaching context, provoking questions and thus deeper understanding. Peppy allows exploration of the relative effects of hydrogen bonding (and electrostatic interactions more generally), backbone ϕ/ψ angles, basic chemical structure and steric effects on polypeptide structure in an accessible format that is novel, dynamic and fun to use. As well as describing the implementation and use of Peppy, we discuss the outcomes of deploying Peppy in undergraduate biochemistry courses.

STATEMENT

Protein structure is inherently dynamic and three-dimensional, but traditional teaching tools are static and/or two-dimensional. We have developed a virtual reality teaching tool, Peppy, that facilitates undergraduate teaching of the principles of protein structure. We outline how Peppy works in terms of how it is used and what goes on ‘under the hood’. We then illustrate its use in undergraduate teaching, where its playful nature stimulated exploration and, thus, deeper understanding.