bluuebunny/crossref_metadata_2025 huggingface dataset:
Using a Standardized Patient to Improve Collaboration and Problem Solving Skills With CPAP Usage in the Home
Authors: Williams Margaret G. , Ruhs Joan
Published: May 2018

A review of literature revealed a lack of research pertaining to nurses' or student nurses' knowledge of continuous positive airway pressure (CPAP) and the ability to troubleshoot CPAP malfunction. This study sought to answer the following questions: What are associate degree nursing (ADN) students' knowledge, interdisciplinary communication, and problem-solving skills regarding patients' home use of CPAP? Is there a change after participation in a simulation with a patient on CPAP in home setting? Twenty-one ADN students enrolled in small Midwest college participated. A preexperimental design of one group pretest posttest was used. Each student completed a demographic questionnaire, Mayo High Performance Teamwork Scale, Interprofessional collaborative simulation experience survey, and a CPAP knowledge base survey before and upon completion of the simulation. There were no changes in students' comfort, baseline knowledge, and basic understanding regarding CPAP. However, after the simulation, students described more detailed problem-solving skills, which included using respiratory therapists, durable medical equipment providers, and community resources. On the Mayo High Performance Teamwork Scale, all 16 items demonstrated improved scores (baseline mean = 21.65 and postsimulation mean = 25.6).
Bundle Payment Program Initiative
Authors: Peiritsch Heather
Published: May 2018

With the passage of the Affordable Care Act, The Centers for Medicare and Medicaid (CMS) introduced a new value-based payment model, the Bundle Payment Care Initiative. The CMS Innovation (Innovation Center) authorized hospitals to participate in a pilot to test innovative payment and service delivery models that have a potential to reduce Medicare expenditures while maintaining or improving the quality of care for beneficiaries. A hospital-based home care agency, Abington Jefferson Health Home Care Department, led the initiative for the development and implementation of the Bundled Payment Program. This was a creative and innovative method to improve care along the continuum while testing a value-based care model.
Hypoglycemia in Diabetes Mellitus
Authors: Freeland Barbara
Published: May 2018

Hypoglycemia is a serious acute complication of diabetes treatment. Recognizing the risk factors and taking steps to prevent low blood glucose should be a part of self-management education for all people taking glucose-lowering medications. It is important for home care clinicians to evaluate their patient's understanding of hypoglycemia and the appropriate treatment options.
Culturally Sensitive Care for Asian Immigrants
Authors: Ko Arthur , Turner Jill
Published: May 2018

The number of Asian immigrants has risen dramatically in recent decades, making them the fastest growing immigrant group in the United States. Home healthcare clinicians are expected to meet the healthcare needs of patients regardless of their ethnic or cultural background, but this can be challenging without a basic understanding of the patient's culture. This article is intended to provide information about the cultural traditions and health conditions clinicians may encounter when caring for patients and families who have immigrated to the United States from the top five Asian countries as determined by the U.S. Census, and concludes with resources that home healthcare clinicians can utilize when engaging in patient education.
Educating and Engaging Older Adults in the Sure Steps® Fall Prevention Program
Authors: Ciance Karin L.
Published: May 2018

Falls are the leading cause of fatal and nonfatal injuries among adults 65 years and older. Each year, one in three older adults experiences a fall, and people who fall are more likely to fall again. According to the National Council on Aging (2017), instituting evidence-based falls prevention programs can significantly decrease falls. The purpose of this article is to describe a pilot study that examined the impact of the Sure Steps® Fall Prevention Program on incidence of falls among adults 65 and older living in their home. A convenience sample of 10 community-dwelling participants aged 65 and older was recruited. After the Sure Steps® Fall Prevention Program was implemented, participants were contacted by telephone monthly for 1 year. None of the participants reported falls during that time. Based on the findings of this pilot study, the Visiting Nurse Association implemented the Sure Steps® Fall Prevention Program into their other four clinical sites.
Establishing Relationships and Navigating Boundaries When Caring for Children With Medical Complexity at Home
Authors: Nageswaran Savithri , Golden Shannon L.
Published: May 2018

Children with medical complexity receive care from many healthcare providers including home healthcare nurses. The objective of our study, based on a conceptual framework, was to describe the relationships between parents/caregivers of children with medical complexity and home healthcare nurses caring for these children. We collected qualitative data in 20 semistructured in-depth interviews (15 English, 5 Spanish) with 26 primary caregivers of children with medical complexity, and 4 focus groups of 18 home healthcare nurses inquiring about their experiences about home healthcare nursing services for children with medical complexity. During an iterative analysis process, we identified recurrent themes related to caregiver–nurse relationships. Our study showed that: (1) caregiver–nurse relationships evolved over time and were determined by multiple factors; (2) communication and trust were essential to the establishment of caregiver–nurse relationships; (3) both caregivers and nurses described difficulties of navigating physical, professional, personal, and emotional boundaries, and identified strategies to maintain these boundaries; and (4) good caregiver–nurse relationships helped in the care of children with medical complexity, reduced caregiver burden, resulted in less stress for nurses, and was a factor in nurse retention. We conclude that trusted relationships between caregivers and nurses are important to the home care of children with medical complexity. Interventions to develop and maintain good caregiver–nurse relationships are necessary.
A Resource Guide to Improve Nursing Care and Transition to Self-Care for Patients With Ostomies
Authors: Berti-Hearn Linda , Elliott Brenda
Published: May 2018

Clinical management of patients with an ostomy can be complex and stressful. With only 10% of Wound Ostomy Incontinence Nurses working in home health, home healthcare nurses need to be knowledgeable about care of patients with new ostomies. This article provides an overview of the resources available to guide nurses caring for ostomy patients. In addition, resources nurses can share with patients as they transition into the community are provided.
Online Resources to Support Clinical Practice
Authors: Ko Arthur , Turner Jill
Published: May 2018

Evidence-based practice requires access to practice guidelines, research articles, and other resources; however, home healthcare clinicians can face barriers when seeking health information. The purpose of this article is to provide home care clinicians with: a) free resources available on the internet, b) suggestions for searching and evaluating health information found on the internet, and c) opportunities for free continuing education for home healthcare clinicians.
Pediatric Nasogastric Tubes in the Home
Authors: Northington LaDonna , Lyman Beth , Moore Candice , Guenter Peggi
Published: May 2018

One of the dilemmas facing home healthcare nurses is the placement of a nasogastric tube (NGT) in the home setting coupled with being assured and confident that the NGT tip is in the correct position, that is, the stomach. There are very limited data to address the issue of management of an NGT in the home care setting with even less guidance for the pediatric population. Therefore, home healthcare nurses must use agency policy and procedures coupled with their own education, knowledge, experience, and skills when performing this procedure. These may vary from agency to agency, thus providing inconsistencies in teaching and techniques.
Home Delivered Meals to Older Adults
Authors: Gualtieri Marie C. , Donley Amy M. , Wright James D. , Vega Sara Strickhouser
Published: May 2018

The United States is witnessing a growing aging population stemming in part from medical advancements allowing people to live decades longer than previous generations. Simultaneously, food insecurity among older adults has increased, and is projected to get worse as the Baby Boomer generation ages. This review focuses on an assistance program for older adults: home-delivered meals. Specifically, we focus on the effects of Meals on Wheels (MOW) on the physical and emotional well-being of older adults, and the wide variety of procedural and operational issues that various MOW programs around the country experience. Findings from the literature highlight the positive outcomes these programs have on their clients. Although there have been recent budget cut threats from the federal government, evidence suggests that more funding should be allocated so these programs can provide services to everyone in need, and even expand what they are able to offer to older adults.
Multiple Sclerosis
Authors: Capriotti Teri , Noel Julia , Brissenden Simone
Published: May 2018

Multiple sclerosis (MS) is a chronic neurologic disease and the most common cause of nontraumatic disability in young adults in the United States. It strikes adults in the prime of life and can gradually diminish physical and mental function, affect relationships, employment, financial capacity, and independence. Neurologic symptoms fluctuate in a pattern of remissions and exacerbations for the majority of those with MS. A multidisciplinary treatment approach is essential. There are a wide number of medications that can be used. Treating the disease at an early stage within the first 5 years of clinical symptom onset is optimal. Home healthcare clinicians can use assessment tools to evaluate disease progression, teach the patient and family how to live with the disorder, and monitor the patient for medication side effects.
Autopsy Features of Fatal Donkey Attack
Authors: Fogel Lajos , Varga Gyula , Hubay Marta , Felszeghy Endre , Varga Peter , Byard Roger W.
Published: May 2018

Lethal donkey attacks have very rarely been described. The case of a 65-year-old man who was found deceased on a country road with 2 domestic donkeys nearby is, therefore, reported. Examination of the body revealed contusions and lacerations of the face and scalp, a comminuted fracture of the left maxilla, comminuted fracturing of the right radius and ulna and of the left anterior superior iliac spine, a flail chest, and pulmonary contusions. In addition, there were bite marks on the left thigh, right buttock, right axilla/upper arm, and left cheek which corresponded to the dental arcades of the donkeys. Death had resulted from blunt chest trauma due to an attack by 1 or 2 donkeys. Deaths and serious injuries are much more commonly caused by horses; however, this case shows that even domesticated donkeys may also rarely be capable of inflicting significant trauma and so should be approached with circumspection.
Selected Case From the Arkadi M. Rywlin International Pathology Slide Club: Peritoneal Lipofuscinosis and Deciduosis in Pregnancy
Authors: Gunawardane Dimuth N. , Allen Philip W.
Published: May 2018

Peritoneal lipofuscinosis is a very rarely recognized condition occurring during pregnancy characterized by brown pigmentation of the omentum and peritoneum, a decidual reaction and benign mesothelial cells. The iron negative pigment, which is likely to be confused with hemosiderin in the hematoxylin and eosin stain, is lipofuscin. The seminar case, apparently the third published, arose in a 37-year-old woman who presented in October 2015 at 24 weeks pregnancy with abdominal pain. Investigations revealed a ruptured left ovarian cyst and rising serum carcinoembryonic antige levels. At laparotomy, there was no free intraperitoneal blood but the omentum and uterine serosa were black. Histology showed lipofuscinosis and a decidual reaction. The patient delivered a normal baby in February 2016 and was clinically well after delivery. A left ovarian endometriotic cyst was removed in February 2017. The patient made a good recovery with no clinically apparent symptoms from the liposuscinosis. We postulate that the endometriotic cyst had ruptured and released blood into the peritoneal cavity in 2015. The iron from the red cells breakdown was then rapidly resorbed because of the pregnancy requirements for iron, leaving lipofuscin in peritoneal macrophages.
Fluorescent In Situ Hybridization in Surgical Pathology Practice
Authors: Gupta Ruta , Cooper Wendy A. , Selinger Christina , Mahar Annabelle , Anderson Lyndal , Buckland Michael E. , O’Toole Sandra A.
Published: May 2018

There have been rapid and significant advances in diagnostic and predictive molecular techniques in recent years with profound impact on patient care. In situ hybridization (ISH) studies have become well entrenched in surgical pathology practice and their role in the evaluation of HER2 in breast carcinoma and their diagnostic utility in soft tissue pathology are well known. Fluorescent ISH is being increasingly used in other sites such as the head and neck and the gynecologic tract. Like most tests in surgical pathology, ISH studies require good quality tissue, correlation with clinical and histopathologic findings, and adherence to guidelines for optimal assay performance and interpretation. Although ISH studies are largely performed in tertiary centers, the tissue is often processed by a variety of laboratories and the referring pathologists are required to discuss the need, relevance, and significance of these tests and the results with their clinical colleagues. Here we review the predictive and diagnostic utility of fluorescent ISH studies in a variety of organ systems, the preanalytical factors that may affect the results, and the pitfalls in the interpretation that all practicing surgical pathologists should be aware of.
Relationships Between Gross Motor Skills and Social Function in Young Boys With Autism Spectrum Disorder
Authors: Holloway Jamie M. , Long Toby M. , Biasini Fred
Published: May 2018

Purpose:

The purpose of this study was to examine the relationship between gross motor skills and social function in young boys with autism spectrum disorder.

Methods:

Twenty-one children with autism spectrum disorder participated in the study. The Peabody Developmental Motor Scales Second Edition and the Miller Function and Participation Scales were used to assess gross motor skills. The Social Skills Improvement System Rating Scales was used to assess social function.

Results:

Moderately high correlations were found between overall gross motor and social skills (r = 0.644) and between the core stability motor subtest and overall social skills (r = −0.672). Specific motor impairments in stability, motor accuracy, and object manipulation scores were predictive of social function.

Conclusions:

This study suggests that motor skills and social function are related in young boys with autism. Implications for physical therapy intervention are also discussed.
A Quality Initiative: A System-Wide Reduction in Serious Medication Events Through Targeted Simulation Training
Authors: Hebbar Kiran B. , Colman Nora , Williams Lorisa , Pina Jessica , Davis Lisa , Bost James E. , Jones Halli , Frank Gary
Published: May 2018

Introduction

Medication administration events (MAEs) are a great concern to the healthcare industry, because they are both common and costly. Pediatric patients pose unique challenges to healthcare systems, particularly regarding the safety of medication administration. Our objectives were to improve adherence to best practices, decrease MAEs, and decrease cost related to error reduction rates by implementing a scenario-based simulation training program for frontline nursing staff in the general care units, emergency departments, and intensive care units within our institution.

Methods

Children's simulation center in conjunction with the medication safety workgroup developed a 2-hour target-specific simulation-based training. This quality initiative focused on implementation of a MAE bundle that included the following three elements: The Five Rights, MedZone, and Independent Double Check. Adherence to the use of bundle elements was monitored via bedside auditing for 18 months after the intervention. This audit was accomplished using an institution-wide MAE reporting system. The 2012 Healthcare Cost and Utilization Project Kids' Inpatient Database and 2014 Children's Hospital Association, Pediatric Health Information System databases were used to estimate cost impact.

Results

A total of 1434 nurses from our intensive care units, emergency departments, and general care inpatient units participated in simulation training. Nursing adherence to the MAE bundle in the 18-month period after simulation increased by 33%, from January 2014 to June 2015. Medication administration event monitoring during the preintervention, intervention, and postintervention periods demonstrated a decrease in error rate from 2.5 events per month to 0.86 events per month This error reduction correlated to an estimated charge savings of $165,000 to $255,000 and a cost impact of $90,000 to $130,000 per year.

Conclusions

Target-specific simulation-based training on a large scale has improved adherence with best practice guidelines and has led to a significant reduction in MAEs.
Short-term Outcomes of Ambulatory Colectomy for 157 Consecutive Patients
Authors: Gignoux Benoit , Gosgnach Marilyn , Lanz Thomas , Vulliez Alexandre , Blanchet Marie-Cecile , Frering Vincent , Faucheron Jean-Luc , Chasserant Philippe
Published: May 2018

Objective:

To evaluate short-term outcomes of laparoscopic colectomy for selected consecutive patients in an ambulatory setting at two institutions.

Background:

Several studies showed that an enhanced recovery protocol for colorectal surgery reduces postoperative morbidity and mortality, and shortens the length of hospital stay. The development of such a program has allowed us to gradually reduce the length of stay for colorectal surgery, until ambulatory management.

Methods:

Between February, 2013 and December, 2016, all patients scheduled for elective laparoscopic colectomy and meeting rigorous criteria for ambulatory surgery were included. Outcome was prospectively studied.

Results:

One hundred fifty-seven patients (70 women) with a median age of 61 years (range 25–82 years) were included. The ambulatory rate for colectomy was 30.5%. Median operative time and length of in-hospital stay were 95 minutes (range 45–232 minutes) and 10.0 hours (range 7–14.7 hours), respectively. The admission rate was 7.0% due to operative difficulties (4 patients), medical reasons (4 patients), and social reasons (3 patients). Outcomes for these patients were uneventful and the median length of hospital stay was 3.1 days (range 1–14 days). An unscheduled consultation was necessary for 30 patients (20.5%). Nine patients required readmission (6.1%), of whom 6 required reoperation (3.8%). The overall 30-day morbidity rate was 24.8%. The mortality rate was 0%.

Conclusions:

This is the first case of consecutive patients undergoing ambulatory colectomy for malignant or benign disease. We demonstrated the feasibility, safety, and reproducibility of outpatient colectomy for selected patients. In our experience, 30% of patients scheduled for elective colectomy can be managed in an ambulatory setting.
Prognostic Impact of Breast-Conserving Therapy Versus Mastectomy of BRCA1/2 Mutation Carriers Compared With Noncarriers in a Consecutive Series of Young Breast Cancer Patients
Authors: van den Broek Alexandra J. , Schmidt Marjanka K. , van ’t Veer Laura J. , Oldenburg Hester S. A. , Rutgers Emiel J. , Russell Nicola S. , Smit Vincent T. H. B. M. , Voogd Adri C. , Koppert Linetta B. , Siesling Sabine , Jobsen Jan J. , Westenend Pieter J. , van Leeuwen Flora E. , Tollenaar Rob A. E. M.
Published: May 2018

Objective:

To investigate the effects of different types of surgery on breast cancer prognosis in germline BRCA1/BRCA2 mutation carriers compared with noncarriers.

Summary of Background Data:

Although breast-conserving therapy (breast-conserving surgery followed by radiotherapy) has been associated with more local recurrences than mastectomy, no differences in overall survival have been found in randomized trials performed in the general breast cancer population. Whether breast-conservation can be safely offered to BRCA1/2 mutation carriers is debatable.

Methods:

The study comprised a cohort of women with invasive breast cancer diagnosed <50 years and treated between 1970 and 2003 in 10 Dutch centers. Germline DNA for BRCA1/2 testing of most-prevalent mutations (covering ∼61%) was mainly derived from paraffin-blocks. Survival analyses were performed taking into account competing risks.

Results:

In noncarriers (N = 5820), as well as in BRCA1 (N = 191) and BRCA2 (N = 70) mutation carriers, approximately half of the patients received breast-conserving therapy. Patients receiving mastectomy followed by radiotherapy had prognostically worse tumor characteristics and more often received systemic therapy. After adjustment for these potential confounders, patients who received breast-conserving therapy had a similar overall survival compared with patients who received mastectomy, both in noncarriers (hazard ratio [HR] = 0.95, confidence interval [CI] = 0.85–1.07, P = 0.41) and BRCA1 mutation carriers (HR = 0.80, CI = 0.42–1.51, P = 0.50). Numbers for BRCA2 were insufficient to draw conclusions. The rate of local recurrences after breast-conserving therapy did not differ between BRCA1 carriers (10-year risk = 7.3%) and noncarriers (10-year risk = 7.9%).

Conclusion:

Our results, together with the available literature, provide reassurance that breast-conserving therapy is a safe local treatment option to offer to BRCA1 mutation carriers with invasive breast cancer.
Differences in Pelvic Floor Symptoms During Pregnancy Between Hispanic and Non-Hispanic White Women
Authors: Saltzman Hanna M. , Egger Marlene J. , Bardsley Tyler , Ding Qian , Shaw Janet M. , Nygaard Ingrid E.
Published: May 2018

Objectives

This study aimed to describe and compare pelvic floor symptoms and symptom burden between nulliparous Hispanic and non-Hispanic white women in the third trimester of pregnancy and to determine, in women with stress urinary incontinence (SUI), whether bother differs between groups, adjusted for UI severity.

Methods

In this cross-sectional analysis, participants completed the Epidemiology of Prolapse and Incontinence and Incontinence Severity Index questionnaires. We compared differences in symptom domains between groups using logistic regression and tested the effect of ethnicity on bother in women with SUI using linear regression.

Results

The sample comprised 418 non-Hispanic white and 154 Hispanic women. Prevalence rates of symptom domains ranged from 5.0% and 7.1% for pelvic organ prolapse to 95.2% and 94.2% for overactive bladder in non-Hispanic white and Hispanic women, respectively. After adjusting age, height, weight, education, physical activity, and gestational age, non-Hispanic whites had 2.37-fold increased odds (95% confidence interval, 1.44–3.92) for defecatory dysfunction and had nonsignificant increases in other symptom domains. Non-Hispanic whites were more likely to endorse symptoms in 3 or more domains than Hispanic women (58.9% vs 40.3%, respectively; P = 0.0001). Given the same UI severity (Incontinence Severity Index), Hispanic women with SUI reported 7.5 points greater bother (Epidemiology of Prolapse and Incontinence) than non-Hispanic white women (P = 0.07).

Conclusions

After adjustment, we found few differences in the prevalence of pelvic floor symptom domains between Hispanic and non-Hispanic white women, apart from defecatory dysfunction. If differences by ethnicity in other pelvic floor symptoms exist, they do not seem to originate during the first pregnancy.
Effect of Morbid Obesity on Midurethral Sling Efficacy for the Management of Stress Urinary Incontinence
Authors: Elshatanoufy Solafa , Matthews Alexandra , Yousif Mairy , Jamil Marcus , Gutta Sravanthi , Gill Harmanjit , Galvin Shelley L. , Luck Ali M.
Published: May 2018

Objectives

The aim of our study was to assess midurethral sling (MUS) failure rate in the morbidly obese (body mass index [BMI] ≥40 kg/m2) population as compared with normal-weight individuals. Our secondary objective was to assess the difference in complication rates.

Methods

This is a retrospective cohort study. We included all patients who underwent a synthetic MUS procedure from January 1, 2008, to December 31, 2015, in our health system. Failure was defined as reported stress urinary incontinence symptoms or treatment for stress urinary incontinence. Variables collected were BMI; smoking status; comorbidities; perioperative (≤24 hours), short-term (≤30 days), and long-term (>30 days) complications; and follow-up time. Statistics include analysis of variance, χ2 test, logistic regression, Kaplan-Meier method, and Cox regression.

Results

There were 431 patients included in our analysis. Forty-nine patients were in class 3 with a BMI mean of 44.9 ± 5.07 kg/m2. Median follow-up time was 52 months (range, 6–119 months). Class 3 obesity (BMI ≥40 kg/m2) was the only group that had an increased risk of failure when compared with the normal-weight group (P = 0.03; odds ratio, 2.47; 95% confidence interval, 1.09–5.59). Obesity was not a significant predictor of perioperative, short-term, or long-term postoperative complications (P = 0.19, P = 0.28, and P = 0.089, respectively) after controlling for other comorbidities.

Conclusions

Patients in the class 3 obesity group who are treated with an MUS are 2 times as likely to fail when compared with those in the normal-weight category on long-term follow-up with similar low complication rates.
Long-Term Cognitive and Psychological Functioning in Post–Electroconvulsive Therapy Patients
Authors: Miller Michelle L. , Luu Hien , Gaasedelen Owen , Hahn-Ketter Amanda E. , Elmore Alexis , Dezhkam Naseem , Bayless John , Moser David J. , Whiteside Douglas M.
Published: May 2018

Objective

Electroconvulsive therapy (ECT) is associated with positive outcomes for treatment-resistant mood disorders in the short term. However, there is limited research on long-term cognitive or psychological changes beyond 1 year after -ECT. This study evaluated long-term outcomes in cognitive functioning, psychiatric symptoms, and quality of life for individuals who had undergone ECT.

Methods

Eligible participants (N = 294) who completed a brief pre-ECT neuropsychological assessment within the last 14 years were recruited for a follow-up evaluation; a limited sample agreed to follow-up testing (n = 34). At follow-up, participants were administered cognitive measures (Repeatable Battery for the Assessment of Neuropsychological Status [RBANS], Wide Range Achievement Test-4 Word Reading, Trail Making Test, Wechsler Adult Intelligence Scale—Fourth Edition Letter Number Sequence and Digit Span, and Controlled Oral Word Association Test), along with emotional functioning measures (Beck Depression Inventory—Second Edition [BDI-II] and Beck Anxiety Inventory) and the World Health Organization Quality of Life–BREF quality of life measure. Follow-up-testing occurred on average (SD) 6.01 (3.5) years after last ECT treatment.

Results

At follow-up, a paired t test showed a large and robust reduction in mean BDI-II score. Scores in cognitive domains remained largely unchanged. A trend was observed for a mean reduction in RBANS visual spatial scores. Lower BDI-II scores were significantly associated with higher RBANS scores and improved quality of life.

Conclusions

For some ECT patients, memory, cognitive functioning, and decreases in depressive symptoms can remain intact and stable even several years after ECT. However, the selective sampling at follow-up makes these results difficult to generalize to all post-ECT patients. Future research should examine what variables may predict stable cognitive functioning and a decline in psychiatric symptoms after ECT.
PBMC Fixation and Processing for Chromium Single-Cell RNA Sequencing
Authors: Chen Jinguo , Cheung Foo , Shi Rongye , Zhou Huizhi , Wenrui Wenrui , Consortium CHI , Candia Julián , Kotliarov Yuri , Stagliano Katie R. , Tsang John S.
Published: May 2018

Background

Interest in single-cell transcriptomic analysis is growing rapidly, especially for profiling rare or heterogeneous populations of cells. In almost all reported works investigators have used live cells, which introduces cell stress during preparation and hinders complex study designs. Recent studies have indicated that cells fixed by denaturing fixative can be used in single-cell sequencing, however they did not usually work with most types of primary cells including immune cells.

Methods

The methanol-fixation and new processing method was introduced to preserve human peripheral blood mononuclear cells (PBMCs) for single-cell RNA sequencing (scRNA-Seq) analysis on 10X Chromium platform.

Results

When methanol fixation protocol was broken up into three steps: fixation, storage and rehydration, we found that PBMC RNA was degraded during rehydration with PBS, not at cell fixation and up to three-month storage steps. Resuspension but not rehydration in 3X saline sodium citrate (SSC) buffer instead of PBS preserved PBMC RNA integrity and prevented RNA leakage. Diluted SSC buffer did not interfere with full-length cDNA synthesis. The methanol-fixed PBMCs resuspended in 3X SSC were successfully implemented into 10X Chromium standard scRNA-seq workflows with no elevated low quality cells and cell doublets. The fixation process did not alter the single-cell transcriptional profiles and gene expression levels. Major subpopulations classified by marker genes could be identified in fixed PBMCs at a similar proportion as in live PBMCs. This new fixation processing protocol also worked in several other fixed primary cell types and cell lines as in live ones.

Conclusions

We expect that the methanol-based cell fixation procedure presented here will allow better and more effective batching schemes for a complex single cell experimental design with primary cells or tissues.
Structural basis for selective stalling of human ribosome nascent chain complexes by a drug-like molecule
Authors: Li Wenfei , Ward Fred R. , McClure Kim F. , Chang Stacey Tsai-Lan , Montabana Elizabeth , Liras Spiros , Dullea Robert , Cate Jamie H. D.
Published: May 2018

Small molecules that target the ribosome generally have a global impact on protein synthesis. However, the drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small subset of proteins by an unknown mechanism. In high-resolution cryo-electron microscopy (cryo-EM) structures of human ribosome nascent chain complexes stalled by PF846, PF846 binds in the ribosome exit tunnel in a newly-identified and eukaryotic-specific pocket formed by the 28S ribosomal RNA (rRNA), and redirects the path of the nascent polypeptide chain. PF846 arrests the translating ribosome in the rotated state that precedes mRNA and tRNA translocation, with peptidyl-tRNA occupying a mixture of A/A and hybrid A/P sites, in which the tRNA 3’-CCA end is improperly docked in the peptidyl transferase center. Using mRNA libraries, selections of PF846-dependent translation elongation stalling sequences reveal sequence preferences near the peptidyl transferase center, and uncover a newly-identified mechanism by which PF846 selectively blocks translation termination. These results illuminate how a small molecule selectively stalls the translation of the human ribosome, and provides a structural foundation for developing small molecules that inhibit the production of proteins of therapeutic interest.
Highly Multiplexed Single-Cell RNA-seq for Defining Cell Population and Transcriptional Spaces
Authors: Gehring Jase , Park Jong Hwee , Chen Sisi , Thomson Matthew , Pachter Lior
Published: May 2018

We describe a universal sample multiplexing method for single-cell RNA-seq in which cells are chemically labeled with identifying DNA oligonucleotides. Analysis of a 96-plex perturbation experiment revealed changes in cell population structure and transcriptional states that cannot be discerned from bulk measurements, establishing a cost effective means to survey cell populations from large experiments and clinical samples with the depth and resolution of single-cell RNA-seq.
Decreased mitochondrial metabolic requirements in fasting animals carry an oxidative cost
Authors: Salin Karine , Villasevil Eugenia M. , Anderson Graeme J. , Auer Sonya K. , Selman Colin , Hartley Richard C. , Mullen William , Chinopoulos Christos , Metcalfe Neil B.
Published: May 2018

Many animals experience periods of food shortage in their natural environment. It has been hypothesised that the metabolic responses of animals to naturally‐occurring periods of food deprivation may have long‐term negative impacts on their subsequent life‐history.

In particular, reductions in energy requirements in response to fasting may help preserve limited resources but potentially come at a cost of increased oxidative stress. However, little is known about this trade‐off since studies of energy metabolism are generally conducted separately from those of oxidative stress.

Using a novel approach that combines measurements of mitochondrial function with in vivo levels of hydrogen peroxide (H2O2) in brown trout (Salmo trutta), we show here that fasting induces energy savings in a highly metabolically active organ (the liver) but at the cost of a significant increase in H2O2, an important form of reactive oxygen species (ROS).

After a 2‐week period of fasting, brown trout reduced their whole‐liver mitochondrial respiratory capacities (state 3, state 4 and cytochrome c oxidase activity), mainly due to reductions in liver size (and hence the total mitochondrial content). This was compensated for at the level of the mitochondrion, with an increase in state 3 respiration combined with a decrease in state 4 respiration, suggesting a selective increase in the capacity to produce ATP without a concomitant increase in energy dissipated through proton leakage. However, the reduction in total hepatic metabolic capacity in fasted fish was associated with an almost two‐fold increase in in vivo mitochondrial H2O2 levels (as measured by the MitoB probe).

The resulting increase in mitochondrial ROS, and hence potential risk of oxidative damage, provides mechanistic insight into the trade‐off between the short‐term energetic benefits of reducing metabolism in response to fasting and the potential long‐term costs to subsequent life‐history traits.
Maternal density stress and coccidian parasitism: Synergistic effects on overwinter survival in root voles
Authors: Yang Yan‐Bin , Shang Guo‐Zhen , Du Shou‐Yang , Zhang Xin , Wu Yan , Bian Jiang‐Hui
Published: May 2018

Individuals in poor physiological condition are known to be more susceptible to infection that, once it occurs, further deteriorates the individuals' conditions, making them even more susceptible to infection and leading to death. This vicious synergy between the host condition and infection has recently been proposed to be among the key factors determining the oscillation characteristics in natural populations. Field studies that directly test such a hypothesis, however, are currently scarce, and the physiological traits involved remain largely unclear.

In this field study, we systematically examined the synergistic effects of maternal stress and coccidian parasitic interaction on the physiological conditions and overwinter survival of offspring in the root vole (Microtus oeconomus) via repeated live trapping and measurements of faecal corticosterone metabolite (FCM) levels and immunocompetence in captured animals.

We found that maternal density stress significantly increased FCM levels and both the prevalence and intensity of coccidian infection in offspring, significantly suppressed offspring immunocompetence and reduced offspring overwinter survival. Coccidian infection significantly potentiated increases in FCM levels and exacerbated the immune suppression induced by maternal density stress. Coccidian infection also significantly accelerated a decrease in overwinter survival and a population decline in maternal‐density‐stressed populations.

Our findings indicate that both stress and immune systems are involved in the synergistic process through which stressors and parasites interact with the host to influence the fitness of individuals and cause a population decline in the natural environment.

A plain language summary is available for this article.
Acceleration or deceleration of litter decomposition by herbivory depends on nutrient availability through intraspecific differences in induced plant resistance traits
Authors: Burghardt Karin T. , Bradford Mark A. , Schmitz Oswald J.
Published: May 2018

Herbivores often induce changes in plant defensive chemistry or nutrient content that may respectively inhibit or promote microbial decomposition of senesced litter. Often the directional impact of herbivores on decomposition is considered to be a property of a species or ecosystem. While rarely explored, plasticity in the induction of defensive strategies across environmental gradients may also result in divergent impacts of herbivores on decomposition (deceleration vs. acceleration).

Here, we examined how soil nutrient conditions determine legacy effects of herbivory, using nine goldenrod genotypes grown across four levels of nutrient supply and with or without grasshopper herbivory. In this species, herbivory induces defensive traits in genotypes grown in high nutrient conditions but induces tolerance (compensatory growth) in low nutrient conditions. We combined senesced litter from each treatment with a common soil inoculum in microcosms and measured soil respiration and litter mass loss over 100 days as estimates of decomposition.

Plant genotype, nutrient environment, and herbivory each altered decomposition. The legacy effect of herbivory overwhelmed the positive effect of high soil nutrient supply on decomposition. This significant herbivory × nutrient environment interaction meant that herbivore‐induced plants grown in high nutrient environments produced litter that was more resistant to microbial breakdown than litter from the same genotype not exposed to herbivores. But the opposite occurred at low nutrient levels where litter from herbivore‐induced plants was most readily decomposed. Furthermore, we mechanistically tie treatment‐induced changes in leaf traits to decomposition rates. Lastly, we demonstrate a significant correlation between herbivore growth rates on living tissue and decomposition efficiency by the microbial community of senesced tissue, suggesting that herbivores and microbes perceive the “quality” of the induced substrate similarly.

Synthesis. Herbivore‐induced changes in leaf palatability and trait expression due to defense induction or compensatory growth can cascade through to either inhibit or promote the decomposability of leaf litter within a single species. Here, the key determinant of which occurs is the soil fertility environment of the goldenrod clone. These findings offer mechanistic understanding of how spatial heterogeneity in ecosystem process rates may be generated by spatial variation in herbivory and nutrient availability.
Reduction in polyamine catabolism leads to spermine‐mediated airway epithelial injury and induces asthma features
Authors: Jain V. , Raina S. , Gheware A. P. , Singh R. , Rehman R. , Negi V. , Murray Stewart T. , Mabalirajan U. , Mishra A. K. , Casero R. A. , Agrawal A. , Ghosh B.
Published: May 2018

Background

Airway epithelial injury is a crucial component of acute and severe asthma pathogenesis and a promising target for treatment of refractory asthma. However, the underlying mechanism of epithelial injury remains poorly explored. Although high levels of polyamines, mainly spermine, have been found in asthma and comorbidity, their role in airway epithelial injury and the cause of their altered levels in asthma have not been explored.

Methods

We measured key polyamine metabolic enzymes in lung samples from normal and asthmatic subjects and in mice with OVA‐induced allergic airway inflammation (AAI). Polyamine metabolism was modulated using pharmacologic/genetic modulators. Epithelial stress and apoptosis were measured by TSLP levels and TUNEL assay, respectively.

Results

We found loss of the polyamine catabolic enzymes spermidine/spermine‐N (1)‐acetyltransferase‐1 (SAT1) and spermine oxidase (SMOX) predominantly in bronchial epithelial cells (BECs) of human asthmatic lung samples and mice with AAI. In naïve mice, SAT1 or SMOX knockdown led to airway hyper‐responsiveness, remodeling, and BEC apoptosis. Conversely, in mice with AAI, overexpression of either SAT1 or SMOX alleviated asthmatic features and reduced TSLP levels and BEC apoptosis. Similarly, while pharmacological induction of SAT1 and SMOX using the polyamine analogue bis(ethyl)norspermine (BENSPM) alleviated asthmatic features with reduced TSLP levels and BEC apoptosis, pharmacological inhibition of these enzymes using BERENIL or MDL72527, respectively, worsened them. Spermine accumulation in lungs correlated with BEC apoptosis, and spermine treatment caused apoptosis of human BEAS‐2B cells in vitro.

Conclusions

Spermine induces BEC injury. Induction of polyamine catabolism may represent a novel therapeutic approach for asthma via reversing BEC stress.
Atopic asthma after rhinovirus‐induced wheezing is associated with DNA methylation change in the SMAD3 gene promoter
Authors: Lund R. J. , Osmala M. , Malonzo M. , Lukkarinen M. , Leino A. , Salmi J. , Vuorikoski S. , Turunen R. , Vuorinen T. , Akdis C. , Lähdesmäki H. , Lahesmaa R. , Jartti T.
Published: May 2018

Children with rhinovirus‐induced severe early wheezing have an increased risk of developing asthma later in life. The exact molecular mechanisms for this association are still mostly unknown. To identify potential changes in the transcriptional and epigenetic regulation in rhinovirus‐associated atopic or nonatopic asthma, we analyzed a cohort of 5‐year‐old children (n = 45) according to the virus etiology of the first severe wheezing episode at the mean age of 13 months and to 5‐year asthma outcome. The development of atopic asthma in children with early rhinovirus‐induced wheezing was associated with DNA methylation changes at several genomic sites in chromosomal regions previously linked to asthma. The strongest changes in atopic asthma were detected in the promoter region of SMAD3 gene at chr 15q22.33 and introns of DDO/METTL24 genes at 6q21. These changes were validated to be present also at the average age of 8 years.
Initiating transitional care for adolescents with cystic fibrosis at the age of 12 is both feasible and promising
Authors: Skov M , Teilmann G , Damgaard I N , Nielsen K G , Hertz P G , Holgersen M G , Presfeldt M , Dalager A M S , Brask M , Boisen K A
Published: May 2018

Aim

Adolescence is a vulnerable period in cystic fibrosis, associated with declining lung function. This study described, implemented and evaluated a transition programme for adolescents.

Methods

We conducted a single centre, nonrandomised and noncontrolled prospective programme at the cystic fibrosis centre at Copenhagen University Hospital Rigshospitalet from 2010 to 2011, assessing patients aged 12–18 at baseline and after 12 months. Changes implemented included staff training on communication, a more youth‐friendly feel to the outpatient clinic, the introduction of youth consultations partly alone with the adolescent, and a parents’ evening focusing on cystic fibrosis in adolescence. Lung function and body mass index (BMI) were measured monthly and adolescents were assessed for their readiness for transition and quality of life at baseline and 12 months.

Results

We found that 40 (98%) of the eligible patients participated and youth consultations were successfully implemented with no dropouts. The readiness checklist score increased significantly over the one‐year study period, indicating increased readiness for transfer and self‐care. Overall quality of life, lung function and BMI remained stable during the study period.

Conclusion

A well‐structured transition programme for cystic fibrosis patients as young as 12 years of age proved to be both feasible and sustainable.
The evolution of the policy environment for climate change migration in Bangladesh: Competing narratives, coalitions and power
Authors: Geun Ji Hyeng
Published: May 2018

In spite of an enormous increase in attention to climate migration in Bangladesh, institutional weaknesses have meant that unplanned migration has triggered social issues. This situation requires investigation of the main challenges and opportunities in institutional capacity and policy development for climate change induced migration. Drawing on different narratives, networks and power status of stakeholders, this study identifies two competing coalitions: ‘in‐situ’ coalition, which shares the belief that migration is a failure of adaptation, and ‘ex‐situ’ coalition adhering to the emerging slogan of “migration as adaptive strategy.” The differentiated powers of two coalitions to some extent leave the agenda of climate migration in the policy domain as a subject of informal institutional capacity rather than a formal regulatory framework. Consequently, the evolution of the policy environment for climate migration depends on how effectively a greater policy space is determined by narratives, coalitions and power. Through a political economy lens, this article seeks to clarify the potential approaches to extending the policy space regarding climate migration in Bangladesh, first by improving ideological pluralism in international climate change finance, and, second, enhancing the bottom‐up process for resource mobilization. In short, the evolution of the policy environment for climate change largely depends on the political power of the ‘ex‐situ’ coalition.
Comparative evaluation of the clonogenic capacity of periodontal ligament fibroblasts in Hank's balanced salt solution and egg albumen: An in vitro study
Authors: Shah Dimpi , Sulkshane Prasad , Lalwani Rutika , Pawar Sagar , Teni Tanuja , Kakade Adesh
Published: May 2018

Background/Aim

The type of storage media for short‐term storage of an avulsed tooth is a critical determinant for the success of tooth replantation. If immediate replantation of an avulsed tooth is not possible, it is advised to store the tooth in a suitable storage medium. The viability and clonogenicity of periodontal ligament fibroblasts (PDLF) determines the success of replantation of an avulsed tooth. The aim of this study was to evaluate the effect on the clonogenic capacity of PDLF's upon storage in Hank's balanced salt solution (HBSS) and egg albumen.

Methods

Fibroblast cell culture was established from a human premolar tooth extracted for orthodontic purposes. The PDLF cells thus obtained were treated with either Dulbecco's modified Eagle's medium (DMEM; as a positive control), HBSS, or egg albumen for different durations at room temperature and then allowed to grow in DMEM medium until visible colonies appeared which were then fixed, stained, and scored manually.

Results

With increase in the duration of storage in both egg albumen as well as HBSS, there was a reduction in the clonogenic capacity of the PDLF's as compared to DMEM. However, storage in egg albumen led to a significant reduction in the clonogenic capacity of PDLF's (8%‐16% for egg albumen) compared to HBSS (80%‐90%).

Conclusion

Due to its limited ability to support the clonogenicity of PDLF's, egg albumen is a poor storage medium for an avulsed tooth compared to either DMEM or HBSS.