bluuebunny/crossref_metadata_2025 huggingface dataset:
The Economic and Social Burden of the 2014 Ebola Outbreak in West Africa
Authors: Huber Caroline , Finelli Lyn , Stevens Warren
Published: April 2018

Background

The 2014 Ebola virus disease (EVD) outbreak in West Africa was more devastating than all previous EVD outbreaks combined; however, many estimates of its economic burden did not capture its significant social costs. This study aimed to review all currently available estimates, identify social components missed by these estimates, and generate a comprehensive cost of the 2014 EVD outbreak.

Methods

We conducted a systematic review of the grey (reports produced by nonprofit or nongovernmental organizations, government, or industry) and published literature to identify current estimates of the burden of the outbreak. Based on the findings of this review, we identified 6 key areas absent or underestimated from previous estimates and calculated the underestimated social costs using estimates from the literature and extrapolation.

Results

Current estimates of the economic burden of the outbreak range from $2.8 to $32.6 billion in lost gross domestic product. We estimated the comprehensive economic and social burden from the 2014 EVD outbreak to be $53.19 billion (2014 USD). The most significant component, $18.8 billion, was deaths from non-Ebola causes.

Conclusions

A more complete understanding of the burden of the 2014 EVD outbreak underscores the value of interventions that can mitigate or reduce the severity of future outbreaks.
Decreased Rescue Analgesic Use with Elagolix Treatment in Women with Endometriosis-Associated Pain [35G]
Authors: Taylor Hugh S. , Diamond Michael , Surrey Eric , Schwefel Brittany , Snabes Michael , Peloso Paul
Published: April 2018

INTRODUCTION:

Rescue analgesic use was evaluated in two phase 3 studies, wherein 6-months (M) of elagolix (an oral, non-peptide GnRH antagonist) treatment was associated with improved dysmenorrhea and nonmenstrual pelvic pain compared to placebo in women with endometriosis-associated pain.

METHODS:

Elaris EM-I (N=871) and Elaris EM-II (N=815) were randomized, double-blind, 6M, placebo-controlled phase 3 studies evaluating two elagolix doses (150mg once daily [QD] or 200mg twice daily [BID]) in women with moderate/severe endometriosis-associated pain. Women could use either naproxen and/or a single opioid as rescue analgesic (opioid varied by country). Daily pill counts were recorded in an electronic-diary.

RESULTS:

At baseline, the mean daily rescue analgesic pill count ranged 0.7-0.9 across studies/doses. The mean percent decrease from baseline in average daily rescue analgesic pill count (any analgesic) was significantly greater compared to placebo for elagolix 200mg BID at M3 in Elaris EM-I and M6 in both studies (M6-least-squares mean percent change; Elaris EM-I:placebo=-24.7%, 150mg QD=-40.3%, P=0.121, 200mg BID=-59.9%, P<0.001; Elaris EM-II:placebo=-23.1%, 150mg QD=-26.9%, P=0.810, 200mg BID=-75.3%, P<0.001). At M6 in each study, rescue analgesic use, based on percent change from baseline in average daily pill count, was significantly reduced compared to placebo for naproxen and opioid pill count in the 200mg BID dose group.

CONCLUSION:

It was previously shown that elagolix treatment (150mg QD and 200mg BID) decreased pain in women with moderate/severe endometriosis-associated pain at M3 and M6. The current analysis shows that women treated with elagolix 200mg BID had the greatest decrease in rescue analgesic use compared to placebo at M6.
Noninvasive Tracking of Anesthesia Neurotoxicity in the Developing Rodent Brain
Authors: Makaryus Rany , Lee Hedok , Robinson John , Enikolopov Grigori , Benveniste Helene
Published: April 2018

Background

Potential deleterious effect of multiple anesthesia exposures on the developing brain remains a clinical concern. We hypothesized that multiple neonatal anesthesia exposures are more detrimental to brain maturation than an equivalent single exposure, with more pronounced long-term behavioral consequences. We designed a translational approach using proton magnetic resonance spectroscopy in rodents, noninvasively tracking the neuronal marker N-acetyl-aspartate, in addition to tracking behavioral outcomes.

Methods

Trajectories of N-acetyl-aspartate in anesthesia naïve rats (n = 62, postnatal day 5 to 35) were determined using proton magnetic resonance spectroscopy, creating an “N-acetyl-aspartate growth chart.” This chart was used to compare the effects of a single 6-h sevoflurane exposure (postnatal day 7) to three 2-h exposures (postnatal days 5, 7, 10). Long-term effects on behavior were separately examined utilizing novel object recognition, open field testing, and Barnes maze tasks.

Results

Utilizing the N-acetyl-aspartate growth chart, deviations from the normal trajectory were documented in both single and multiple exposure groups, with z-scores (mean ± SD) of –0.80 ± 0.58 (P = 0.003) and –1.87 ± 0.58 (P = 0.002), respectively. Behavioral testing revealed that, in comparison with unexposed and single-exposed, multiple-exposed animals spent the least time with the novel object in novel object recognition (F(2,44) = 4.65, P = 0.015), traveled the least distance in open field testing (F(2,57) = 4.44, P = 0.016), but exhibited no learning deficits in the Barnes maze.

Conclusions

Our data demonstrate the feasibility of using the biomarker N-acetyl-aspartate, measured noninvasively using proton magnetic resonance spectroscopy, for longitudinally monitoring anesthesia-induced neurotoxicity. These results also indicate that the neonatal rodent brain is more vulnerable to multiple anesthesia exposures than to a single exposure of the same cumulative duration.
The effect of Cobb angle correction on spinal length gain in patients with adolescent idiopathic scoliosis
Authors: Ghandhari Hassan , Ameri Ebrahim , Safari Mir Bahram , Kheirabadi Habib , Asl Hadi S. , Zarghampour Manijeh , Behzadmehr Razieh , Fouladi Daniel F.
Published: April 2018

The relationship between curve correction and spinal length gain in adolescent idiopathic scoliosis was examined. A total of 102 patients who underwent posterior spinal correction and fusion alone or in combination with anterior spinal correction and fusion (ASF) were studied. The Cobb angle correction, increase in the main thoracic length, T1–L5 spinal length gain, and T1–L5 spinal length gain/Cobb angle correction were reported. The length gain/Cobb angle correction value was not significantly associated with sex, fusion approach, and the number of fused levels. Surgical T1–L5 spinal length gain (mm) equaled (70.20)−(3.51)×(degrees of Cobb angle correction)+(0.08)×(degrees of Cobb angle correction)2.
Assessment of Proximal Junctional Kyphosis and Shoulder Balance With Proximal Screws versus Hooks in Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis
Authors: Pahys Joshua M. , Vivas Andrew C. , Samdani Amer F. , Cunn Gregory , Betz Randal R. , Newton Peter O. , Cahill Patrick J.
Published: April 2018

Study Design.

A retrospective review of a prospectively collected multicenter database.

Objective.

To assess the effect of proximal hooks versus screws on proximal junctional kyphosis (PJK) as well as shoulder balance in otherwise all pedicle screw (>80%) posterior spinal fusion (PSF) constructs in adolescent idiopathic scoliosis (AIS).

Summary of Background Data.

Less rigid forms of fixation at the top of constructs in degenerative lumbar PSF have been postulated to decrease the risk of PJK.

Methods.

A multicenter AIS surgical database was reviewed to identify all patients who underwent PSF with all pedicle screw (>80%) constructs and minimum 2-year follow-up. Patients in the “hook” group had two hooks used at the top of the construct, whereas the “screw” group used only pedicle screws at all levels.

Results.

A total of 354 patients were identified, 274 (77%) in the screw group, and 80 (23%) in the hook group. There were no significant preoperative differences with regards to curve type, coronal/sagittal Cobb angle, or curve flexibility for either group. At 2 years post-op, the coronal Cobb correction was similar for both groups (60%). There was no difference in correction of shoulder asymmetry and T1 rib angle, including when the groups were matched for preoperative shoulder balance. PJK, defined as the sagittal Cobb angle between the uppermost instrumented and uninstrumented vertebrae, was similar for the screw versus hook group as well (7.1° vs. 6.2°, P = 0.2).

Conclusion.

The use of different anchors (pedicle screws vs. hooks) at the top of an otherwise all pedicle screw PSF construct for AIS did not have any significant bearing on the correction of shoulder asymmetry and coronal Cobb angle at 2 years postoperative. There was also no significant difference in the magnitude of PJK or incidence of marked PJK (>15°) between either group at 2 years.

Level of Evidence: 3
Prenatal exposure to perfluoroalkyl substances
Authors: Shoaff Jessica , Papandonatos George D. , Calafat Antonia M. , Chen Aimin , Lanphear Bruce P. , Ehrlich Shelley , Kelsey Karl T. , Braun Joseph M.
Published: April 2018

Background:

Prenatal perfluoroalkyl substance (PFAS) exposure has been associated with reduced birth weight and excess child adiposity, but the relationship between PFAS and early life growth is unknown.

Objective:

To determine if prenatal PFAS exposure was associated with birth weight, body composition, and growth until 2 years of age.

Methods:

In a prospective cohort of women and their children from Cincinnati, OH, we quantified perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) in pregnant women’s serum. We used linear regression to estimate associations of PFAS with birth weight z-scores (n = 345) and linear mixed models to estimate associations with repeated weight and length/height measurements (n = 334) at 4 weeks and 1 and 2 years of age, after adjusting for sociodemographic, perinatal, nutritional, and environmental factors.

Results:

We found nonsignificant inverse associations between PFAS and infant birth weight. For example, each log2 increase in PFOA was associated with a 0.03 SD reduction in birth weight z-score (95% confidence interval [CI] = −0.17, 0.10). Compared to associations with birth weight, we observed stronger associations between PFAS and child anthropometry from 4 weeks to 2 years. For instance, each log2 increase in PFOA was associated with a 0.12 SD decrease in BMI z-score (95% CI = −0.25, 0.01). We did not observe any differences in growth rate associated with PFAS.

Conclusions:

We observed inverse associations between prenatal serum PFAS concentrations and anthropometry until 2 years of age. Prenatal serum PFAS concentrations were not associated with growth rate in the first 2 years of life.
Establishing Radiological Screening Levels for Defense-related Uranium Mine (DRUM) Sites on BLM Land Using a Recreational Future-use Scenario
Authors: Brown Steven H. , Edge Russel , Elmer John , McDonald Michael
Published: April 2018

Thousands of former uranium mining sites in the United States, primarily in the southwestern states of Colorado, Arizona, New Mexico, Arizona, and Utah, are being identified and evaluated to assess their potential for causing public and environmental impacts. The common radiological contaminant of concern that characterizes these sites is naturally occurring uranium ore and associated wastes that may have been left behind postmining. The majority of these sites were abandoned and in general, are referred to as abandoned uranium mines, regardless of the government authority currently managing the land or in some cases, assigned responsibility for the oversight of assessment and remediation. The U.S. Department of Energy has identified over 4,000 defense-related uranium mine sites from which uranium ore was purchased by the U.S. government for nuclear defense programs prior to 1970. U.S. Department of Energy has established a program to inventory and perform environmental screening on defense-related uranium mine sites. The focus of this paper is the approximately 2,400 defense-related uranium mine sites located on federal land managed by the Bureau of Land Management and the U.S. Forest Service. This paper presents the results of an analysis to develop radiological screening criteria for U.S. Department of Energy’s defense-related uranium mine sites that can be used as input to the overall ranking of these sites for prioritization of additional assessment, reclamation, or remedial actions. For these sites managed by Bureau of Land Management, public access is typically limited to short-term use, primarily for recreational purposes. This is a broad category that can cover a range of possible activities, including camping, hiking, hunting, biking, all-terrain vehicle use, and horseback riding. The radiological screening levels were developed by calculating the radiological dose to future recreational users of defense-related uranium mine sites assuming a future camper spends two weeks per year at the site engaged in recreational activities. Although a number of possible exposure pathways were included in this analysis (inhalation and ingestion of dust and soil, radon and progeny inhalation, and gamma radiation exposure from the soil), it is desirable as a practical matter to determine what gamma exposure rate would ensure that the annual acceptable exposure as determined by the regulatory authority will not be exceeded in the future. Because these sites are generally remote and located in semiarid environments, traditional exposure scenarios often applied in these types of analyses (e.g., subsistent farmers and ranchers), including exposure pathways for the ingestion of locally grown food products and water, were not considered relevant to short-term recreational use.
Radiation Protection for Interventional Fluoroscopy: Results of a Survey Among Dutch Hospitals
Authors: Bijwaard Harmen , Valk Doreth , de Waard-Schalkx Ischa
Published: April 2018

A survey was conducted among 20 Dutch hospitals about radiation protection for interventional fluoroscopy. This was a follow-up of a previous study in 2007 that led to several recommendations for radiation protection for interventional fluoroscopy. The results indicate that most recommendations have been followed. However, radiation-induced complications from interventional procedures are still often not recorded in the appropriate register. Furthermore, even though professionals with appropriate training in radiation protection are usually involved in interventional procedures, this often is not the case when these procedures are carried out outside the radiology department. Although this involvement is not required by Dutch law, it is recommended to have radiation protection professionals present more often at interventional procedures. Further improvements in radiation protection for interventional fluoroscopy may come from a comparison of dose-reducing practices among hospitals, the introduction of diagnostic reference levels for interventional procedures, and a more thorough form of screening and follow-up of patients.
Anemia in the Elderly
Authors: Girelli Domenico , Marchi Giacomo , Camaschella Clara
Published: April 2018

Anemia affects a substantial fraction of the elderly population, representing a public health problem that is predicted to further increase in coming years because of the demographic drive. Being typically mild, it is falsely perceived as a minor problem, particularly in the elderly with multimorbidity, so that it often remains unrecognized and untreated. Indeed, mounting evidence indicates that anemia in the elderly (AE) is independently associated with disability and other major negative outcomes, including mortality. AE is generally multifactorial, but initial studies suggested that etiology remains unexplained in near one‐third of cases. This proportion is consistently declining due to recent advances highlighting the role of several conditions including clonal hematopoiesis, “inflammaging,” correctable androgen deficiency in men, and under‐recognized iron deficiency. Starting from a real‐world case vignette illustrating a paradigmatic example of anemia in an elderly patient with multimorbidity, we review the main clinical and pathophysiological aspect of AE, giving some practical insights into how to manage similar cases.
CHECKPOINT INHIBITOR IMMUNE THERAPY
Authors: Dalvin Lauren A. , Shields Carol L. , Orloff Marlana , Sato Takami , Shields Jerry A.
Published: April 2018

Purpose:

To review immune checkpoint inhibitor indications and ophthalmic side effects.

Methods:

A literature review was performed using a PubMed search for publications between 1990 and 2017.

Results:

Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab). These medications upregulate the immune system and cause autoimmune-like side effects. Ophthalmic side effects most frequently manifest as uveitis (1%) and dry eye (1–24%). Other side effects include myasthenia gravis (n = 19 reports), inflammatory orbitopathy (n = 11), keratitis (n = 3), cranial nerve palsy (n = 3), optic neuropathy (n = 2), serous retinal detachment (n = 2), extraocular muscle myopathy (n = 1), atypical chorioretinal lesions (n = 1), immune retinopathy (n = 1), and neuroretinitis (n = 1). Most inflammatory side effects are managed with topical or periocular corticosteroids, but advanced cases require systemic corticosteroids and cessation of checkpoint inhibitor therapy.

Conclusion:

Checkpoint inhibitors enhance the immune system by releasing inhibition on T cells, with risk of autoimmune-like side effects. Ophthalmologists should include immune-related adverse events in their differential when examining cancer patients with new ocular symptoms.
Interleukin-6 trans-signaling and pathological low back pain in patients with Paget disease of bone
Authors: Rendina Domenico , De Filippo Gianpaolo , Postiglione Loredana , Covelli Bianca , Ricciardone Margherita , Guillaume Séverine , Di Spigna Gaetano , Selleri Carmine , Merlotti Daniela , Bianciardi Simone , Materozzi Maria , Muscariello Riccardo , De Pascale Francesca , D'Elia Lanfranco , Nuti Ranuccio , Strazzullo Pasquale , Gennari Luigi
Published: April 2018

The interleukin (IL)-6 biological system plays a key role in the pathogenesis of Paget disease (PD) of bone and pathological bone pain. Bone pain, particularly in the lower back region, is the most frequent symptom in patients with PD. This case–control study aimed to evaluate the relationship between the IL-6 system and low back pain (LBP) in patients with PD. We evaluated 85 patients with PD, with the disease localized in the lumbar spine, pelvis, and/or sacrum, and classified them based on the presence or absence of LBP, before and after aminobisphosphonate treatment. We also examined 32 healthy controls without LBP. Before treatment, IL-6 levels in patients with PD were higher than those in the controls, without difference between patients with or without LBP. Patients with PD with LBP (35/85) showed higher IL-6-soluble receptor (sIL-6R) and lower soluble glycoprotein (sgp) 130 levels compared with both patients with PD without LBP and controls (sIL-6R: 46.9 ± 7.4 vs 35.4 ± 8.6 vs 29.9 ± 4.2 ng/mL; sgp130: 307.2 ± 35.4 vs 341.4 ± 41.4 vs 417.1 ± 58.5 ng/mL, respectively). Paget disease remission, 6 months after treatment, is associated with LBP improvement. This phenomenon is associated with reduced sIL-6R levels and increased sgp130 levels in patients with PD with LBP at the baseline. Considering the biological properties of IL-6, sIL-6R, and sgp130, the results of the study suggest that the perception of LBP in patients with PD could be linked to an enhanced transmission of IL-6 signal in the specialized neural system activated by nociceptors.
Changes in Heart Failure Symptoms are Associated With Changes in Health-related Quality of Life Over 12 Months in Patients With Heart Failure
Authors: Heo Seongkum , Moser Debra K. , Lennie Terry A. , Fischer Mary , Kim JinShil , Lee Mikyoung , Walsh Mary N. , Ounpraseuth Songthip
Published: April 2018

Purpose:

Patients with heart failure (HF) have notably poor health-related quality of life (HRQOL). A 5-point improvement in HRQOL is associated with reduction in hospitalization and mortality rates. Heart failure symptoms are associated with poor HRQOL, but little is known about whether changes in HF symptoms lead to changes in HRQOL over time. Therefore, we examined the association of changes in HF symptoms with changes in overall, physical, and emotional aspects of HRQOL over a 12-month period, controlling for typical covariates.

Methods:

Data on HF symptoms and HRQOL (Minnesota Living Heart Failure questionnaire) were collected from 94 patients with HF (mean age, 58 years; 58.5% female) at baseline and 12-month follow-up. Psychosocial factors (depressive symptoms, perceived control, and social support), behavioral factors (medication adherence and sodium intake), sociodemographic and clinical factors (age, comorbidities, and body mass index), and a physical factor (functional status) were collected at baseline. Multiple and logistic regression analyses were used to analyze the data.

Results:

In complete models, changes in HF symptoms were associated with changes in the total HRQOL (P < .001) and the physical (P < .001) and emotional (P < .001) aspects of HRQOL over 12 months, controlling for all the factors. Changes in HF symptoms were significantly associated with the likelihood of at least a 5-point improvement in HRQOL (P = .001), controlling for covariates.

Conclusions:

Improvement in HF symptoms was associated with improvement in HRQOL over 12 months. Thus, development and delivery of interventions that target improvement in HF symptoms may improve HRQOL.
Living With Dementia in Correctional Settings: A Case Report
Authors: Peacock Shelley , Hodson Alexandra , MacRae Rhoda , Peternelj-Taylor Cindy
Published: April 2018

The prison population is aging at an alarming rate and many older persons have the potential to develop dementia while in prison. This case report aims to explore the needs of older people living with dementia in prison and discusses the interventions that exist to address these needs. As the condition progresses, persons with dementia become increasingly reliant on the support of others for their health and well-being because of the increasing complexity of physical healthcare and psychosocial needs. Very few interventions are cited in the research literature regarding the use, acceptability, and/or effectiveness of programming for people living with dementia in prison. To support the unique and complex needs of these persons, research is needed to guide the development of evidence-informed dementia programs and services as well as consideration of interdisciplinary collaboration with community organizations.
Sustained Breastfeeding and Related Factors for Late Preterm and Early Term Infants
Authors: Kuhnly Joan Esper
Published: April 2018

The purpose of this pilot study was to determine the prevalence of sustained breastfeeding in late preterm and early term breastfeeding infants at 1 and 2 months of age and to identify the factors that were related to sustained breastfeeding. Subjects were identified through purposive sampling and completed the Breastfeeding Self-Efficacy Scale and data were collected on lactation support, hospital course details, and demographic factors. At 1 and 2 months of age, structured telephone interviews determined the current feeding status and postdischarge lactation support. Of 126 mothers, 82% sustained breastfeeding at 1 month and 71.2% at 2 months. Factors associated with sustained breastfeeding at 2 months included a college education (P = .014), higher day 1 breastfeeding scores (P = .007), higher Breastfeeding Self-Efficacy scores (P = .046), and continued maternal skin-to-skin contact (P = .007). High after day 1 breastfeeding scores were associated with sustained breastfeeding at 1 month (P = .000) and 2 months (P = .001). Unsustained breastfeeding at 1 and 2 months was associated with the occurrence of supplemental feedings (P = .001) and pumping at discharge (1 month, P = .002; 2 months, P = .015). Identifying the factors associated with the high-sustained breastfeeding rate in this population helps nurses focus on how to best support their breastfeeding experience.
The Necessity for Post-Maneuver Restrictions in the Treatment of Benign Paroxysmal Positional Vertigo: An Updated Meta-Analysis of the Literature
Authors: Cromwell Christina , Tyler Jordan , Nobbs Rachael , Hockaday Adam , Donnelly Sean , Clendaniel Richard
Published: April 2018

Objective:

Many studies have published conflicting results regarding the necessity of post-maneuver postural restrictions following treatment of benign paroxysmal positional vertigo (BPPV). The purpose of this meta-analysis is to complete an updated, comprehensive review to determine best practice following a repositioning maneuver (RM).

Data Sources:

PubMed, CINAHL, and Embase were searched through July 2016. The reference lists of the selected studies were searched for studies that were not identified in the electronic database searches.

Study Selection:

Studies investigating the effect of post-maneuver postural restrictions on RM treatment efficacy were included.

Data Extraction:

The methodology, number of participants, type of RM administered, post-maneuver restrictions implemented, outcome measures, and results for each study were recorded.

Data Synthesis:

Following data extraction, heterogeneity and homogeneity values of included studies were determined. Risk ratios and random effects values were obtained to determine effect size.

Results:

Eleven studies were included in the meta-analysis. The results of 739 total subjects were analyzed, 362 of which received post-maneuver postural restrictions and 377 of which did not. Meta-analysis revealed that there was not a statistically significant difference in treatment success rates between patients who received post-maneuver postural restrictions (90.3%) and those who did not (81.7%) (p = 0.095).

Conclusions:

There was no statistically significant difference found in treatment efficacy between subjects who received post-maneuver postural restrictions and those who did not. Based on the results of this meta-analysis, if there is any benefit from prescribing the postural restrictions, it is likely to be a small marginal improvement in outcomes.
In-hospital cardiac arrest: are we overlooking a key distinction?
Authors: Moskowitz Ari , Holmberg Mathias J. , Donnino Michael W. , Berg Katherine M.
Published: April 2018

Purpose of review

To review the epidemiology, peri-arrest management, and research priorities related to in-hospital cardiac arrest (IHCA) and explore key distinctions between IHCA and out-of-hospital cardiac arrest (OHCA) as they pertain to the clinician and resuscitation scientist.

Recent findings

IHCA is a common and highly morbid event amongst hospitalized patients in the United States. As compared with patients who experience an OHCA, patients who experience an IHCA tend to have more medical comorbidities, have a witnessed arrest, and be attended to by professional first responders. Further, providers resuscitating patients from IHCA commonly have access to tools and information not readily available to the OHCA responders. Despite these differences, society guidelines for the peri-arrest management of patients with IHCA are often based on data extrapolated from the OHCA population. To advance the care of patients with IHCA, clinicians and investigators should recognize the many important distinctions between OHCA and IHCA.

IHCA is a unique disease entity with an epidemiology and natural history that are distinct from OHCA. In both research and clinical practice, physicians should recognize these distinctions so as to advance the care of IHCA victims.
APRIL is Involved in the Proliferation and Metastasis of Acute Lymphoblastic Leukemia Cells
Authors: Sun Baolan , Xia Zhengting , Cai Fuying , Wang Pengbo , Xu Meiyu , Wu Youjia
Published: April 2018

Our previous work showed that a proliferation-inducing ligand (APRIL) was involved in the development of acute lymphoblastic leukemia (ALL) in children. However, the precise role of APRIL in ALL remains unknown. To investigate this issue, we silenced and overexpressed APRIL in Nalm-6 ALL cells using short hairpin RNA targeting the APRIL gene and recombinant human APRIL, respectively, and evaluated the effects on cell proliferation, apoptosis, and migration. APRIL mRNA and APRIL and matrix metalloproteinase-2 protein levels were evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blott, respectively. We found that APRIL expression was reduced by shRNA-mediated knockdown in Nalm-6 cells; this was associated with a decrease in cell proliferation (P<0.05). APRIL knockdown increased apoptosis (P<0.01) but suppressed cell migration along with matrix metalloproteinase-2 protein level. Overexpressing recombinant human APRIL had the opposite effects in each case (P<0.05). These results demonstrate a link between APRIL expression and ALL development and suggest that APRIL is a potential therapeutic target for ALL treatment.
Trends in Imaging Findings, Interventions, and Outcomes Among Children With Isolated Head Trauma
Authors: Coon Eric R. , Newman Thomas B. , Hall Matt , Wilkes Jacob , Bratton Susan L. , Schroeder Alan R.
Published: April 2018

Objective

The aim was to analyze the impact of decreased head computed tomography (CT) imaging on detection of abnormalities and outcomes for children with isolated head trauma.

Methods

The study involves a multicenter retrospective cohort of patients younger than 19 years presenting for isolated head trauma to emergency departments in the Pediatric Health Information System database from 2003 to 2015. Patients directly admitted or transferred to another facility and those with a discharge diagnosis code for child maltreatment were excluded. Outcomes were ascertained from administrative and billing data. Trends were tested using mixed effects logistic regression, accounting for clustering within hospitals and adjusted for age, sex, insurance type, race, presence of a complex chronic condition, and hospital-level case mix index.

Results

Between 2003 and 2015, 306,041 children presented for isolated head trauma. The proportion of children receiving head CT imaging was increasing until 2008, peaking at just under 40%, before declining to 25% by 2015. During the recent period of decreased head CT imaging, the detection of skull fractures (odds ratio [OR]/year, 0.96; 95% confidence interval [CI], 0.95–0.97) and intracranial bleeds (OR/year, 0.96; 95% CI, 0.94–0.97), hospitalization (OR/year, 0.96; 95% CI, 0.95–0.96), neurosurgery (OR/year, 0.91; 95% CI, 0.87–0.95), and revisit (OR/year, 0.98; 95% CI, 0.96–1.00) also decreased, without significant changes in mortality (OR/year, 0.93; 95% CI, 0.84–1.04) or persistent neurologic impairment (OR/year, 1.03; 95% CI, 0.92–1.15).

Conclusions

The recent decline in CT scanning in children with isolated head trauma was associated with a reduction in detection of intracranial abnormalities, and a concomitant decrease in interventions, without measurable patient harm.
Teaching Point-of-Care Lung Ultrasound to Novice Pediatric Learners
Authors: Soon Aun Woon , Toney Amanda Greene , Stidham Timothy , Kendall John , Roosevelt Genie
Published: April 2018

Objective

To assess whether Web-based teaching is at least as effective as traditional classroom didactic in improving the proficiency of pediatric novice learners in the image acquisition and interpretation of pneumothorax and pleural effusion using point-of-care ultrasound (POCUS).

Methods

We conducted a randomized controlled noninferiority study comparing the effectiveness of Web-based teaching to traditional classroom didactic. The participants were randomized to either group A (live classroom lecture) or group B (Web-based lecture) and completed a survey and knowledge test. They also received hands-on training and completed an objective structured clinical examination. The participants were invited to return 2 months later to test for retention of knowledge and skills.

Results

There were no significant differences in the mean written test scores between the classroom group and Web group for the precourse test (absolute difference, −2.5; 95% confidence interval [CI], −12 to 6.9), postcourse test (absolute difference, 2.0; 95% CI, −1.4, 5.3), and postcourse 2-month retention test (absolute difference, −0.8; 95% CI, −9.6 to 8.1). Similarly, no significant differences were noted in the mean objective structured clinical examination scores for both intervention groups in postcourse (absolute difference, 1.9; 95% CI, −4.7 to 8.5) and 2-month retention (absolute difference, −0.6; 95% CI, −10.7 to 9.5).

Conclusions

Web-based teaching is at least as effective as traditional classroom didactic in improving the proficiency of novice learners in POCUS. The usage of Web-based tutorials allows a more efficient use of time and a wider dissemination of knowledge.
Quantitation of Perfused Lung Volume Using Hybrid SPECT/CT Allows Refining the Assessment of Lung Perfusion and Estimating Disease Extent in Chronic Thromboembolic Pulmonary Hypertension
Authors: Derlin Thorsten , Kelting Catharina , Hueper Katja , Weiberg Desiree , Meyer Katrin , Olsson Karen M. , Thackeray James T. , Welte Tobias , Bengel Frank M. , Hoeper Marius M.
Published: April 2018

Background

We evaluated the feasibility of perfusion SPECT/CT for providing quantitative data for estimation of perfusion defect extent in chronic thromboembolic pulmonary hypertension (CTEPH).

Methods

Thirty patients with CTEPH underwent 99mTc–human serum albumin lung perfusion SPECT/CT. Perfusion defects were quantified using 3 different methods: (1) visual, semiquantitative scoring of perfusion defect extent in each lung segment, (2) threshold-based segmentation of perfused lung volumes, and (3) threshold-based segmentation of perfused lung volumes divided by segmented lung volumes at CT (perfusion index). Imaging findings were correlated with right-sided heart catheterization results and N-terminal pro–B-type natriuretic peptide. Receiver operating characteristic analysis was performed to identify SPECT thresholds for mean pulmonary arterial pressure (PAPm) greater than 50 mm Hg.

Results

Assessment of lung perfusion provided similar results using all 3 methods. The perfusion defect score correlated with PAPm (r
s = 0.60, P = 0.0005) and was associated with serum levels of N-terminal pro–B-type natriuretic peptide (r
s = 0.37, P = 0.04). Perfused lung volume (40% threshold, r
s = −0.48, P = 0.007) and perfusion index (40% threshold, r
s = −0.50, P = 0.005) decreased as PAPm increased. Receiver operating characteristic analysis showed that perfusion defect score (sensitivity, 88%; specificity, 77%; area under the curve [AUC] = 0.89, P = 0.001), perfused lung volume (sensitivity, 88%; specificity, 64%; AUC = 0.80, P = 0.01), and perfusion index (sensitivity, 88%; specificity, 64%; AUC = 0.82, P = 0.009) could identify patients with PAPm of greater than 50 mm Hg.

Conclusions

Quantitative analysis of perfusion defects at SPECT is feasible, provides a measure of disease severity, and correlates with established clinical parameters. Quantitation of perfusion SPECT may refine the diagnostic approach in CTEPH providing a quantitative imaging biomarker, for example, for therapy monitoring.
Newly Diagnosed Primary Gum Lymphoma on FDG PET/CT
Authors: Zhang Jianhua , Fan Yan , Liu Meng , Li Qian , Wang Rongfu
Published: April 2018

An 81-year-old woman presented a 2-month history of left upper gum swelling. Biopsy of the lesion revealed the diffuse large B-cell lymphoma. 18F-FDG PET/CT scan showed the abnormal high uptake at the left upper gum.
Impact of Breast Surgery in Primary Metastasized Breast Cancer
Authors: Fitzal Florian , Bjelic-Radisic Vesna , Knauer Michael , Steger Günther , Hubalek Michael , Balic Marija , Singer Christian , Bartsch Rupert , Schrenk Peter , Soelkner Lidija , Greil Richard , Gnant Michael
Published: April 2018

Background:

Conflicting evidence exists regarding the value of surgical resection of the primary in stage IV breast cancer patients.

Objective:

The prospective randomized phase III ABCSG-28 POSYTIVE trial evaluated median survival comparing primary surgery followed by systemic therapy to primary systemic therapy in de novo stage IV breast cancer.

Methods:

Between 2011 and 2015, 90 previously untreated stage IV breast cancer patients were randomly assigned to surgical resection of the primary tumor followed by systemic therapy (Arm A) or primary systemic therapy (Arm B) in Austria. Overall survival (OS) was defined as the primary study endpoint.

Results:

The trial was stopped early due to poor recruitment. Ninety patients (45 arm A, 45 arm B) were included; median follow-up was 37.5 months. Patients in the surgery arm had more cT3 breast cancer (22.2% vs 6.7%) and more cN2 staging (15.6% vs 4.4%). Both groups were well balanced with respect to the type of first-line systemic treatment. Median survival in arm A was 34.6 months, versus 54.8 months in the nonsurgery arm [hazard ratio (HR) 0.691, 95% confidence interval (95% CI) 0.358–1.333; P = 0.267]; time to distant progression was 13.9 months in the surgery arm and 29.0 months in the nonsurgery arm (HR 0.598, 95% CI 0.343–1.043; P = 0.0668).

Conclusion:

The prospective phase III trial ABCSG-28 (POSYTIVE) could not demonstrate an OS benefit for surgical resection of the primary in breast cancer patients presenting with de novo stage IV disease.
Evolutionary trade-offs and the structure of polymorphisms
Authors: Sheftel Hila , Szekely Pablo , Mayo Avi , Sella Guy , Alon Uri
Published: April 2018

Populations of organisms show genetic differences called polymorphisms. Understanding the effects of polymorphisms is important for biology and medicine. Here, we ask which polymorphisms occur at high frequency when organisms evolve under trade-offs between multiple tasks. Multiple tasks present a problem, because it is not possible to be optimal at all tasks simultaneously and hence compromises are necessary. Recent work indicates that trade-offs lead to a simple geometry of phenotypes in the space of traits: phenotypes fall on the Pareto front, which is shaped as a polytope: a line, triangle, tetrahedron etc. The vertices of these polytopes are the optimal phenotypes for a single task. Up to now, work on this Pareto approach has not considered its genetic underpinnings. Here, we address this by asking how the polymorphism structure of a population is affected by evolution under trade-offs. We simulate a multi-task selection scenario, in which the population evolves to the Pareto front: the line segment between two archetypes or the triangle between three archetypes. We find that polymorphisms that become prevalent in the population have pleiotropic phenotypic effects that align with the Pareto front. Similarly, epistatic effects between prevalent polymorphisms are parallel to the front. Alignment with the front occurs also for asexual mating. Alignment is reduced when drift or linkage is strong, and is replaced by a more complex structure in which many perpendicular allele effects cancel out. Aligned polymorphism structure allows mating to produce offspring that stand a good chance of being optimal multi-taskers in at least one of the locales available to the species.

This article is part of the theme issue ‘Self-organization in cell biology’.
Self-organization principles of intracellular pattern formation
Authors: Halatek J. , Brauns F. , Frey E.
Published: April 2018

Dynamic patterning of specific proteins is essential for the spatio-temporal regulation of many important intracellular processes in prokaryotes, eukaryotes and multicellular organisms. The emergence of patterns generated by interactions of diffusing proteins is a paradigmatic example for self-organization. In this article, we review quantitative models for intracellular Min protein patterns inEscherichia coli, Cdc42 polarization inSaccharomyces cerevisiaeand the bipolar PAR protein patterns found inCaenorhabditis elegans. By analysing the molecular processes driving these systems we derive a theoretical perspective on general principles underlying self-organized pattern formation. We argue that intracellular pattern formation is not captured by concepts such as ‘activators’, ‘inhibitors’ or ‘substrate depletion’. Instead, intracellular pattern formation is based on the redistribution of proteins by cytosolic diffusion, and the cycling of proteins between distinct conformational states. Therefore, mass-conserving reaction–diffusion equations provide the most appropriate framework to study intracellular pattern formation. We conclude that directed transport, e.g. cytosolic diffusion along an actively maintained cytosolic gradient, is the key process underlying pattern formation. Thus the basic principle of self-organization is the establishment and maintenance of directed transport by intracellular protein dynamics.

This article is part of the theme issue ‘Self-organization in cell biology’.
Fluid flows shaping organism morphology
Authors: Alim Karen
Published: April 2018

A dynamic self-organized morphology is the hallmark of network-shaped organisms like slime moulds and fungi. Organisms continuously reorganize their flexible, undifferentiated body plans to forage for food. Among these organisms the slime mould
Physarum polycephalum
 has emerged as a model to investigate how an organism can self-organize their extensive networks and act as a coordinated whole. Cytoplasmic fluid flows flowing through the tubular networks have been identified as the key driver of morphological dynamics. Inquiring how fluid flows can shape living matter from small to large scales opens up many new avenues for research. This article is part of the theme issue ‘Self-organization in cell biology’.
Ordering of myosin II filaments driven by mechanical forces: experiments and theory
Authors: Dasbiswas Kinjal , Hu Shiqiong , Schnorrer Frank , Safran Samuel A. , Bershadsky Alexander D.
Published: April 2018

Myosin II filaments form ordered superstructures in both cross-striated muscle and non-muscle cells. In cross-striated muscle, myosin II (thick) filaments, actin (thin) filaments and elastic titin filaments comprise the stereotypical contractile units of muscles called sarcomeres. Linear chains of sarcomeres, called myofibrils, are aligned laterally in registry to form cross-striated muscle cells. The experimentally observed dependence of the registered organization of myofibrils on extracellular matrix elasticity has been proposed to arise from the interactions of sarcomeric contractile elements (considered as force dipoles) through the matrix. Non-muscle cells form small bipolar filaments built of less than 30 myosin II molecules. These filaments are associated in registry forming superstructures (‘stacks’) orthogonal to actin filament bundles. Formation of myosin II filament stacks requires the myosin II ATPase activity and function of the actin filament crosslinking, polymerizing and depolymerizing proteins. We propose that the myosin II filaments embedded into elastic, intervening actin network (IVN) function as force dipoles that interact attractively through the IVN. This is in analogy with the theoretical picture developed for myofibrils where the elastic medium is now the actin cytoskeleton itself. Myosin stack formation in non-muscle cells provides a novel mechanism for the self-organization of the actin cytoskeleton at the level of the entire cell.

This article is part of the theme issue ‘Self-organization in cell biology’.
Guided by curvature: shaping cells by coupling curved membrane proteins and cytoskeletal forces
Authors: Gov N. S.
Published: April 2018

Eukaryote cells have flexible membranes that allow them to have a variety of dynamical shapes. The shapes of the cells serve important biological functions, both for cells within an intact tissue, and during embryogenesis and cellular motility. How cells control their shapes and the structures that they form on their surface has been a subject of intensive biological research, exposing the building blocks that cells use to deform their membranes. These processes have also drawn the interest of theoretical physicists, aiming to develop models based on physics, chemistry and nonlinear dynamics. Such models explore quantitatively different possible mechanisms that the cells can employ to initiate the spontaneous formation of shapes and patterns on their membranes. We review here theoretical work where one such class of mechanisms was investigated: the coupling between curved membrane proteins, and the cytoskeletal forces that they recruit. Theory indicates that this coupling gives rise to a rich variety of membrane shapes and dynamics, while experiments indicate that this mechanism appears to drive many cellular shape changes.

This article is part of the theme issue ‘Self-organization in cell biology’.
Lipid self-assembly and lectin-induced reorganization of the plasma membrane
Authors: Sych Taras , Mély Yves , Römer Winfried
Published: April 2018

The plasma membrane represents an outstanding example of self-organization in biology. It plays a vital role in protecting the integrity of the cell interior and regulates meticulously the import and export of diverse substances. Its major building blocks are proteins and lipids, which self-assemble to a fluid lipid bilayer driven mainly by hydrophobic forces. Even if the plasma membrane appears—globally speaking—homogeneous at physiological temperatures, the existence of specialized nano- to micrometre-sized domains of raft-type character within cellular and synthetic membrane systems has been reported. It is hypothesized that these domains are the origin of a plethora of cellular processes, such as signalling or vesicular trafficking. This review intends to highlight the driving forces of lipid self-assembly into a bilayer membrane and the formation of small, transient domains within the plasma membrane. The mechanisms of self-assembly depend on several factors, such as the lipid composition of the membrane and the geometry of lipids. Moreover, the dynamics and organization of glycosphingolipids into nanometre-sized clusters will be discussed, also in the context of multivalent lectins, which cluster several glycosphingolipid receptor molecules and thus create an asymmetric stress between the two membrane leaflets, leading to tubular plasma membrane invaginations.

This article is part of the theme issue ‘Self-organization in cell biology’.