bluuebunny/crossref_metadata_2025 huggingface dataset:
A relic of the past: current genetic patterns of the palaeoendemic tree Nothofagus macrocarpa were shaped by climatic oscillations in central Chile
Authors: Mathiasen Paula , Venegas-González Alejandro , Fresia Pablo , Premoli Andrea C
Published: June 2020

Background and Aims

The Mediterranean-type forest of central Chile is considered a ‘biodiversity hotspot’ and a relic of a wider ancient distribution produced by past climatic oscillations. Nothofagus macrocarpa, commonly known as ‘roble de Santiago’, is a threatened palaeoendemic of this forest, poorly represented in the protected area system. This tree has been repeatedly misidentified as the sister species N. obliqua, which has affected its recognition and protection. Only a few populations of N. macrocarpa remain within a matrix of intensive land use that has been affected by recent forest fires. We tested the hypothesis that current populations of N. macrocarpa are a relic state of a previously widespread range, with the aim of contributing to its identification, its biogeographical history and the design of conservation measures using genetic information.

Methods

We analysed remnant N. macrocarpa forests using nuclear (nDNA) and chloroplast DNA (cpDNA) sequences, conducted phylogenetic and phylogeographical analyses to reconstruct its biogeographical history, and assessed microsatellites [simple sequence repeats (SSRs)] to determine contemporary patters of diversity within and among all remnant populations. We also examined the degree of past, current and potential future isolation of N. macrocarpa populations using ecological niche models (ENMs).

Key Results

The species N. macrocarpa was confirmed by nDNA sequences, as previously suggested by chromosomal analysis. Small isolated populations of N. macrocarpa exhibited moderate to high genetic diversity according to SSRs. cpDNA analysis revealed a marked past latitudinal geographical structure, whereas analysis of SSRs did not find such current structure. ENM analyses revealed local expansion–contraction of the N. macrocarpa range during warmer periods, particularly in the northern and central ranges where basal-most cpDNA haplotypes were detected, and recent expansion to the south of the distribution.

Conclusions

Genetic patterns confirm that N. macrocarpa is a distinct species and suggest a marked latitudinal relic structure in at least two evolutionarily significant units, despite contemporary among-population gene flow. This information must be considered when choosing individuals (seeds and/or propagules) for restoration purposes, to avoid the admixture of divergent genetic stocks.
The impact ofSpodoptera exiguaherbivory onMeloidogyne incognita-induced root responses depends on the nematodes’ life cycle stages
Authors: Mbaluto Crispus M , Ahmad Esraa M , Fu Melody , Martínez-Medina Ainhoa , van Dam Nicole M
Published: June 2020

Induced responses to above-ground and below-ground herbivores may interact via systemic signalling in plants. We investigated whether the impact of above-ground herbivory on root-knot nematode-induced responses depends on the nematode’s life cycle stages. Tomato plants were infected with the nematode (Meloidogyne incognita) for 5, 15 or 30 days before receiving Spodoptera exigua caterpillars above-ground. We collected root materials after 24 h of caterpillar feeding. We investigated phytohormones and α-tomatine levels, and the expression of defence and glycoalkaloid metabolism (GAME) marker genes in tomato roots. Nematode infection alone increased the endogenous root levels of jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), α-tomatine and the expression of the GLYCOALKALOID METABOLISM 1 (GAME1) gene mostly at 30 days post-nematode inoculation. Caterpillar feeding alone upregulated Lipoxygenase D and downregulated Basic-β-1-glucanase and GAME1 expression in roots. On nematode-infected plants, caterpillar feeding decreased JA levels, but it increased the expression of Leucine aminopeptidase A. The induction patterns of ABA and SA suggest that caterpillars cause cross-talk between the JA-signalling pathway and the SA and ABA pathways. Our results show that caterpillar feeding attenuated the induction of the JA pathway triggered by nematodes, mostly in the nematodes’ reproduction stage. These results generate a better understanding of the molecular and chemical mechanisms underlying frequent nematode–plant–caterpillar interactions in natural and agricultural ecosystems.
Developmental mechanisms regulating the formation of smooth muscle layers in the mouse uterus†
Authors: Nakajima Tadaaki , Sakai Naoto , Nogimura Miho , Tomooka Yasuhiro
Published: June 2020

Uterine smooth muscle cells differentiate from mesenchymal cells, and gap junctions connect the muscle cells in the myometrium. At the neonatal stage, a uterine smooth muscle layer is situated away from the epithelium when smooth muscle cells are grafted near the epithelium, suggesting that the epithelium plays an important role in differentiation, proliferation, and/or migration of smooth muscle cells. In this study, developmental mechanisms regulating the formation of the smooth muscle layers in the mouse uterus were analyzed using an in vitro culture model. Differentiation of smooth muscle cells occurs at a neonatal stage because ACTA2 gene expression was increased at the outer layer, and GJA1 was not expressed in cellular membranes of uterine smooth muscle cells by postnatal day 15. To analyze the effects of the epithelium on the differentiation of smooth muscle cells, a bulk uterine mesenchymal cell line was established from p53−/− mice at postnatal day 3 (P3US cells). Co-culture with Müllerian ductal epithelial cells (E1 cells) induced repulsive migration of ACTA2-positive cells among bulk P3US cells from E1 cells, but it had no effects on the migration of any of 100% ACTA2-positive or negative smooth muscle cell lines cloned from P3US cells. Thus, uterine epithelial cells indirectly affected the repulsive migration of smooth muscle cells via mesenchymal cells. Conditioned medium by E1 cells inhibited differentiation into smooth muscle cells of clonal cells established from P3US cells. Therefore, the uterine epithelium inhibits the differentiation of stem-like progenitor mesenchymal cells adjacent to the epithelium into smooth muscle cells.
The value of septal rebound stretch analysis for the prediction of volumetric response to cardiac resynchronization therapy
Authors: Salden Odette A E , Zweerink Alwin , Wouters Philippe , Allaart Cornelis P , Geelhoed Bastiaan , de Lange Frederik J , Maass Alexander H , Rienstra Michiel , Vernooy Kevin , Vos Marc A , Meine Mathias , Prinzen Frits W , Cramer Maarten J
Published: June 2020

Aims

Patient selection for cardiac resynchronization therapy (CRT) may be enhanced by evaluation of systolic myocardial stretching. We evaluate whether systolic septal rebound stretch (SRSsept) derived from speckle tracking echocardiography is a predictor of reverse remodelling after CRT and whether it holds additive predictive value over the simpler visual dyssynchrony assessment by apical rocking (ApRock).

Methods and results

The association between SRSsept and change in left ventricular end-systolic volume (ΔLVESV) at 6 months of follow-up was assessed in 200 patients. Subsequently, the additive predictive value of SRSsept over the assessment of ApRock was evaluated in patients with and without left bundle branch block (LBBB) according to strict criteria. SRSsept was independently associated with ΔLVESV (β 0.221, P = 0.002) after correction for sex, age, ischaemic cardiomyopathy, QRS morphology and duration, and ApRock. A high SRSsept (≥optimal cut-off value 2.4) also coincided with more volumetric responders (ΔLVESV ≥ −15%) than low SRSsept in the entire cohort (70.0% and 56.4%), in patients with strict LBBB (83.3% vs. 56.7%, P = 0.024), and non-LBBB (70.7% vs. 46.3%, P = 0.004). Moreover, in non-LBBB patients, SRSsept held additional predictive information over the assessment of ApRock alone since patients that showed ApRock and high SRSsept were more often volumetric responder than those with ApRock but low SRSsept (82.8% vs. 47.4%, P = 0.001).

Conclusion

SRSsept is strongly associated with CRT-induced reduction in left ventricular end-systolic volume and holds additive prognostic information over QRS morphology and ApRock. Our data suggest that CRT patient selection may be improved by assessment of SRSsept, especially in the important subgroup without strict LBBB.

Clinical trial registration

The MARC study was registered at clinicaltrials.gov: NCT01519908.
A case report of isolated severe valve stenosis in a previous tricuspid valve repair: an integrated multimodality imaging and invasive haemodynamic evaluation
Authors: Jensen Jesper Khedri , Frederiksen Christian Alcaraz , Andersen Mads Jønsson , Poulsen Steen Hvitfeldt
Published: June 2020

Background

Tricuspid valve (TV) stenosis is a very rare condition and the aetiology is primarily due to rheumatic disease, carcinoid disease, congenital heart disease, endocarditis, and following degeneration of biological valve prosthesis.

Case summary

We present a 45-year-old man with a rare case of symptomatic TV stenosis (TS) in a previously isolated TV repair. A meticulous multimodality diagnostic approach is presented in order to determine the severity of the TS and to evaluate the right ventricular function.

Discussion

This case report presents an integrated multimodality imaging and haemodynamic approach to evaluate and document the suspicion of development of a symptomatic significant stenosis in a previous TV repair. The initial TV repair was done without ring annuloplasty, because only the anterior leaflet was affected and bicuspidalization of the valve made it patent. In addition, minimizing the amount of implanted material was intended to minimize the risk of reinfection. The final treatment was performed as a TV replacement with insertion of a bioprosthesis.
Association of anticoagulant therapy with risk of dementia among patients with atrial fibrillation
Authors: Kim Daehoon , Yang Pil-Sung , Jang Eunsun , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , Kim Jong-Youn , Sung Jung-Hoon , Pak Hui-Nam , Lee Moon-Hyoung , Lip Gregory Y H , Joung Boyoung
Published: June 2020

Aims

To investigate the risk of dementia in atrial fibrillation (AF) patients treated with different oral anticoagulants (OACs).

Methods and results

This observational, population-based cohort study enrolled 53 236 dementia-free individuals with non-valvular AF who were aged ≥50 years and newly prescribed OACs from 1 January 2013 to 31 December 2016 from the Korean National Health Insurance Service database. Propensity score matching was used to compare the rates of dementia between users of non-vitamin K antagonist oral anticoagulant (NOAC) (dabigatran, rivaroxaban, and apixaban) and warfarin and to compare each individual NOAC with warfarin. Propensity score weighting analyses were also performed. In the study population (41.3% women; mean age: 70.7 years), 2194 had a diagnosis of incident dementia during a mean follow-up of 20.2 months. Relative to propensity-matched warfarin users, NOAC users tended to be at lower risk of dementia [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69–0.90]. When comparing individual NOACs with warfarin, all the three NOACs were associated with lower dementia risk. In pairwise comparisons among NOACs, rivaroxaban was associated with decreased dementia risk, compared with dabigatran (HR 0.83, 95% CI 0.74–0.92). Supplemental propensity-weighted analyses showed consistent protective associations of NOACs with dementia relative to warfarin. The associations were consistent irrespectively of age, sex, stroke, and vascular disease and more prominent in standard dose users of NOAC.

Conclusion

In this propensity-matched and -weighted analysis using a real-world population-based cohort, use of NOACs was associated with lower dementia risk than use of warfarin among non-valvular AF patients initiating OAC treatment.
A unified theory for the circuit of atrioventricular nodal re-entrant tachycardia
Authors: Katritsis Demosthenes G
Published: June 2020

Atrioventricular nodal re-entrant tachycardia (AVNRT) is the most common regular tachycardia in the human, but its exact circuit remains elusive. In this article, recent evidence about the electrophysiological characteristics of AVNRT and new data on the anatomy of the atrioventricular node, are discussed. Based on this information, a novel, unified theory for the nature of the circuit of the tachycardia is presented.
Higher Risk Taking and Impaired Probability Judgment in Behavioral Addiction
Authors: Asaoka Yui , Won Moojun , Morita Tomonari , Ishikawa Emi , Goto Yukiori
Published: June 2020

Background

Accumulating evidence suggests that deficits in decision-making and judgment may be involved in several psychiatric disorders, including addiction. Behavioral addiction is a conceptually new psychiatric condition, raising a debate of what criteria define behavioral addiction, and several impulse control disorders are equivalently considered as types of behavioral addiction. In this preliminary study with a relatively small sample size, we investigated how decision-making and judgment were compromised in behavioral addiction to further characterize this psychiatric condition.

Method

Healthy control subjects (n = 31) and patients with kleptomania and paraphilia as behavioral addictions (n = 16) were recruited. A battery of questionnaires for assessments of cognitive biases and economic decision-making were conducted, as was a psychological test for the assessment of the jumping-to-conclusions bias, using functional near-infrared spectroscopy recordings of prefrontal cortical (PFC) activity.

Results

Although behavioral addicts exhibited stronger cognitive biases than controls in the questionnaire, the difference was primarily due to lower intelligence in the patients. Behavioral addicts also exhibited higher risk taking and worse performance in economic decision-making, indicating compromised probability judgment, along with diminished PFC activity in the right hemisphere.

Conclusion

Our study suggests that behavioral addiction may involve impairments of probability judgment associated with attenuated PFC activity, which consequently leads to higher risk taking in decision-making.
Robust finite-time H∞ control of switched non-linear neutral systems in the presence of multiple disturbances using auxiliary matrices
Authors: Gholami Hadi , Shafiei Mohammad Hossein
Published: June 2020

This paper focuses on finite-time boundedness (FTB) of a class of switched non-linear neutral systems in the presence of multiple disturbances. Based on Lyapunov analysis, Finsler’s lemma and the average dwell-time concept, sufficient conditions are extracted to guarantee the FTB of the system. Using these sufficient conditions, finite-time ${H}_{\infty }$ controllers are designed via state feedback and static output feedback structures. The proposed controllers are less conservative than the existing Lyapunov-based approach and there are many degrees of freedom to achieve feasible linear matrix inequalities. Finally, two examples are simulated to validate the proposed approach and to show that the obtained theoretical results are less conservative than the existing papers.
Dispersive liquid-liquid microextraction based preconcentration of selected pesticides and escitalopram oxalate, haloperidol and olanzapine from wastewater samples prior to determination by GC-MS
Authors: Bozyiğit Gamze Dalgıç , Ayyıldız Merve Fırat , Chormey Dotse Selali , Engin Güleda Onkal , Bakırdere Sezgin
Published: June 2020

A multivariate experimental design was used to attain optimum conditions of a dispersive liquid-liquid microextraction (DLLME) method for preconcentration of pesticides and pharmaceuticals for determination by gas chromatography mass spectrometry (GC-MS). Experimental design enabled parameters to be evaluated for their effects on extraction output as well as their interactive effects. The optimum parameters suggested by the design model were 200 µL of chloroform, 1.96 mL of ethanol and 40 s vortexing period. Limits of detection and quantification (LOD and LOQ) were calculated using linear calibration plots of the analytes developed in the standard concentration range of 2.0 µg/L-2.0 mg/L. Enhancement in detection power of the analytes recorded by the optimized method with respect to direct GC-MS determination (based on LOD values) was in the range of 3.6 and 539 folds. Spiked recovery experiments for municipal, medical and synthetic wastewater samples yielded low recovery results when calculated against aqueous standard solutions. Matrix matched calibration standards were used to mitigate interferences from the waste samples, and the percent recoveries obtained were close to 100%. This established accuracy and applicability of the developed method.
Implied Default Probabilities and Losses Given Default from Option Prices*
Authors: Conrad Jennifer , Dittmar Robert F , Hameed Allaudeen
Published: June 2020

We propose a novel method of estimating default probabilities using equity options data. The resulting default probabilities are highly correlated with estimates of default probabilities extracted from CDS spreads, which assume constant losses given default. Additionally, the option-implied default probabilities are higher in bad economic times and for firms with poorer credit ratings and financial positions. A simple inferred measure of loss given default is related to underlying business conditions, and varies across sectors; the time series properties of this measure are similar after controlling for liquidity effects.
A case of pyometra with a colouterine fistula due to rectal cancer presenting as acute abdomen
Authors: Kanemura Masanori , Yoshida Atsushi , Toji Akihiko , Hashida Sousuke , Murayama Yumi , Iwai Emi
Published: June 2020

Pyometra usually develops in elderly women, and it can be caused by various etiologies. We describe a rare case of pyometra with a colouterine fistula due to rectal cancer presenting as acute abdomen. A 67-year-old woman with purulent vaginal discharge and abdominal distension was referred to our hospital for suspected pyometra. Because the vaginal echogram showed pyometra at her initial medical examination, drainage was performed. Her symptoms subsequently disappeared temporarily, but 4 months later, she developed acute abdomen. The computed tomography scan showed a pelvic mass with expansion of the intestine. The patient underwent en bloc resection of the mass. Histopathologic analysis of the tumor showed rectal cancer with invasion of the uterus and ileum, and a colouterine fistula. Although pyometra due to a colouterine fistula is a very rare condition, the incidence of associated malignancy is considerable. Physicians should be aware of this potential presentation of colorectal cancer.
Acute bilateral renal vein thrombosis diagnosis and management: a case report
Authors: Ghaly Paul , Iliopoulos Jim , Ahmad Mehtab
Published: June 2020

Undifferentiated abdominal pain accounts for a significant proportion of emergency presentations and often presents as a diagnostic dilemma. Renal vein thrombosis (RVT) has many aetiologies including nephrotic syndrome, malignancy, trauma, infection and hypercoagulable states. RVT should be considered in cases of persistent abdominal pain where other, more common, pathologies have been excluded. We present the case of a 42-year-old male with a delayed diagnosis of bilateral RVT after presenting with multiple episodes of intractable abdominal pain and adverse sequelae of this condition. This case report aims to emphasize the importance of prompt RVT recognition and the utility of bedside emergency department (ED) investigations, which can guide initial differential diagnoses of abdominal pain, reduce the delay in diagnosis as well as limit unnecessary investigations.
Integration of silicon and secondary metabolites in plants: a significant association in stress tolerance
Authors: Ahanger Mohammad Abass , Bhat Javaid Akhter , Siddiqui Manzer H , Rinklebe Jörg , Ahmad Parvaiz
Published: June 2020

As sessile organisms, plants are unable to avoid being subjected to environmental stresses that negatively affect their growth and productivity. Instead, they utilize various mechanisms at the morphological, physiological, and biochemical levels to alleviate the deleterious effects of such stresses. Amongst these, secondary metabolites produced by plants represent an important component of the defense system. Secondary metabolites, namely phenolics, terpenes, and nitrogen-containing compounds, have been extensively demonstrated to protect plants against multiple stresses, both biotic (herbivores and pathogenic microorganisms) and abiotic (e.g. drought, salinity, and heavy metals). The regulation of secondary metabolism by beneficial elements such as silicon (Si) is an important topic. Silicon-mediated alleviation of both biotic and abiotic stresses has been well documented in numerous plant species. Recently, many studies have demonstrated the involvement of Si in strengthening stress tolerance through the modulation of secondary metabolism. In this review, we discuss Si-mediated regulation of the synthesis, metabolism, and modification of secondary metabolites that lead to enhanced stress tolerance, with a focus on physiological, biochemical, and molecular aspects. Whilst mechanisms involved in Si-mediated regulation of pathogen resistance via secondary metabolism have been established in plants, they are largely unknown in the case of abiotic stresses, thus leaving an important gap in our current knowledge.
Rice NIN-LIKE PROTEIN 1 rapidly responds to nitrogen deficiency and improves yield and nitrogen use efficiency
Authors: Alfatih Alamin , Wu Jie , Zhang Zi-Sheng , Xia Jin-Qiu , Jan Sami Ullah , Yu Lin-Hui , Xiang Cheng-Bin
Published: June 2020

Nitrogen (N) is indispensable for crop growth and yield, but excessive agricultural application of nitrogenous fertilizers has generated severe environmental problems. A desirable and economical solution to cope with these issues is to improve crop nitrogen use efficiency (NUE). Plant NUE has been a focal point of intensive research worldwide, yet much still has to be learned about its genetic determinants and regulation. Here, we show that rice (Oryza sativa L.) NIN-LIKE PROTEIN 1 (OsNLP1) plays a fundamental role in N utilization. OsNLP1 protein localizes in the nucleus and its transcript level is rapidly induced by N starvation. Overexpression of OsNLP1 improves plant growth, grain yield, and NUE under different N conditions, while knockout of OsNLP1 impairs grain yield and NUE under N-limiting conditions. OsNLP1 regulates nitrate and ammonium utilization by cooperatively orchestrating multiple N uptake and assimilation genes. Chromatin immunoprecipitation and yeast one-hybrid assays showed that OsNLP1 can directly bind to the promoter of these genes to activate their expression. Therefore, our results demonstrate that OsNLP1 is a key regulator of N utilization and represents a potential target for improving NUE and yield in rice.
Comprehensive nucleosome interactome screen establishes fundamental principles of nucleosome binding
Authors: Skrajna Aleksandra , Goldfarb Dennis , Kedziora Katarzyna M , Cousins Emily M , Grant Gavin D , Spangler Cathy J , Barbour Emily H , Yan Xiaokang , Hathaway Nathaniel A , Brown Nicholas G , Cook Jeanette G , Major Michael B , McGinty Robert K
Published: June 2020

Nuclear proteins bind chromatin to execute and regulate genome-templated processes. While studies of individual nucleosome interactions have suggested that an acidic patch on the nucleosome disk may be a common site for recruitment to chromatin, the pervasiveness of acidic patch binding and whether other nucleosome binding hot-spots exist remain unclear. Here, we use nucleosome affinity proteomics with a library of nucleosomes that disrupts all exposed histone surfaces to comprehensively assess how proteins recognize nucleosomes. We find that the acidic patch and two adjacent surfaces are the primary hot-spots for nucleosome disk interactions, whereas nearly half of the nucleosome disk participates only minimally in protein binding. Our screen defines nucleosome surface requirements of nearly 300 nucleosome interacting proteins implicated in diverse nuclear processes including transcription, DNA damage repair, cell cycle regulation and nuclear architecture. Building from our screen, we demonstrate that the Anaphase-Promoting Complex/Cyclosome directly engages the acidic patch, and we elucidate a redundant mechanism of acidic patch binding by nuclear pore protein ELYS. Overall, our interactome screen illuminates a highly competitive nucleosome binding hub and establishes universal principles of nucleosome recognition.
Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae
Authors: Prada-Luengo Iñigo , Møller Henrik D , Henriksen Rasmus A , Gao Qian , Larsen Camilla Eggert , Alizadeh Sefa , Maretty Lasse , Houseley Jonathan , Regenberg Birgitte
Published: June 2020

Circular DNA can arise from all parts of eukaryotic chromosomes. In yeast, circular ribosomal DNA (rDNA) accumulates dramatically as cells age, however little is known about the accumulation of other chromosome-derived circles or the contribution of such circles to genetic variation in aged cells. We profiled circular DNA in Saccharomyces cerevisiae populations sampled when young and after extensive aging. Young cells possessed highly diverse circular DNA populations but 94% of the circular DNA were lost after ∼15 divisions, whereas rDNA circles underwent massive accumulation to >95% of circular DNA. Circles present in both young and old cells were characterized by replication origins including circles from unique regions of the genome and repetitive regions: rDNA and telomeric Y’ regions. We further observed that circles can have flexible inheritance patterns: [HXT6/7circle] normally segregates to mother cells but in low glucose is present in up to 50% of cells, the majority of which must have inherited this circle from their mother. Interestingly, [HXT6/7circle] cells are eventually replaced by cells carrying stable chromosomal HXT6 HXT6/7 HXT7 amplifications, suggesting circular DNAs are intermediates in chromosomal amplifications. In conclusion, the heterogeneity of circular DNA offers flexibility in adaptation, but this heterogeneity is remarkably diminished with age.
The Effectiveness of Medical and Surgical Treatment for Children With Refractory Epilepsy
Authors: Pan Iwen , LoPresti Melissa A , Clarke Dave F , Lam Sandi
Published: June 2020

BACKGROUND

Pediatric refractory epilepsy affects quality of life, clinical disability, and healthcare costs for patients and families.

OBJECTIVE

To show the impact of surgical treatment for pediatric epilepsy on healthcare utilization compared to medically treated pediatric epilepsy over 5 yr.

METHODS

The Pediatric Health Information System database was used to conduct a cohort study using 5 published algorithms. Refractory epilepsy patients treated with antiepileptic medications (AEDs) only or AEDs plus epilepsy surgery between 1/1/2008 and 12/31/2014 were included. Healthcare utilization following the index date at 2 and 5 yr including inpatient, emergency department (ED), and all epilepsy-related visits were evaluated. The propensity scores (PS) method was used to match surgically and medically treated patients. PS. SAS® 9.4 and Stata 14.0 were used for data management and statistical analysis.

RESULTS

A total of 2106 (17.1%) and 10186 (82.9%) were surgically and medically treated. A total of 4050 matched cases, 2025 per each treated group, were included. Compared to medically treated patients, utilization was reduced in the surgical group: at 2 and 5 yr postindex date, there was a reduction of 36% to 37% of inpatient visits and 47% to 50% of ED visits. The total number (inpatient, ED, ambulatory visits) of epilepsy-associated visits were reduced by 39% to 43% in the surgical group compared to the medically treated group. In those who had surgery, the average reduction in AEDs was 16% at 2 and 5 yr after treatment.

CONCLUSION

Patients with refractory epilepsy treated with surgery had significant reductions in healthcare utilization compared with patients treated only with medications.
Decentralization’s Effects on Education and Health: Evidence from Ethiopia
Authors: Faguet Jean-Paul , Khan Qaiser , Kanth Devarakonda Priyanka
Published: June 2020

We explore the effects of decentralization on education and health in Ethiopia using an original database covering all of the country’s regions and woredas (local governments). Ethiopia is a remarkable case in which war, famine and chaos in the 1970s–80s were followed by federalization, decentralization, rapid growth, and dramatic improvements in human development. Did decentralization contribute to these successes? We use time series and panel data analyses to show that decentralization improved net enrollments in primary schools and access to antenatal care for pregnant women. The main channel appears to be institutional, not fiscal. We offer the database as an additional contribution.
Long-term outcomes in systemic lupus erythematosus: trends over time and major contributors
Authors: Arnaud Laurent , Tektonidou Maria G
Published: June 2020

SLE is a chronic autoimmune rheumatic disorder of high heterogeneity in clinical presentation, treatment response and prognosis. Long-term outcomes in SLE have been dramatically improved over the past decades, however, increased morbidity and mortality, especially among young individuals, still exists. Unmet needs include residual disease activity and frequent flares, glucocorticoid treatment dependency and toxicity, comorbidity burden, reduced health-related quality of life, health disparities and damage. The main determinants of long-term outcomes in SLE are age, sex, race/ethnicity, genetic profile, environmental factors including smoking, disease activity, major organ involvement such as lupus nephritis and CNS involvement, comorbidities including cardiovascular disease and serious infections, coexistence with APS, treatment adherence, socio-economic factors and access to care. In this review we discuss trends in long-term outcomes in SLE over the years and major contributors such as genetic, disease-related, treatment, comorbidity, socio-economic and other factors.
Nonclinical Safety Assessment of AMG 553, an Investigational Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Acute Myeloid Leukemia
Authors: Karbowski Christine , Goldstein Rebecca , Frank Brendon , Kim Kei , Li Chi-Ming , Homann Oliver , Hensley Kelly , Brooks Benjamin , Wang Xiaoting , Yan Qinghong , Hernandez Rocio , Adams Gregor , Boyle Michael , Arvedson Tara , Lebrec Herve
Published: June 2020

Feline McDonough Sarcoma-like tyrosine kinase 3 (FLT3), a tyrosine-protein kinase involved in hematopoiesis, is detectable on the cell surface of approximately 80% of leukemia isolates from adult patients with acute myeloid leukemia (AML). AMG 553 is an investigational chimeric antigen receptor (CAR) T-cell immunotherapy for the treatment of AML. FLT3 expression analysis and in vitro and in vivo studies were leveraged to evaluate the nonclinical safety of AMG 553. Cynomolgus monkeys administered autologous anti-FLT3 CAR T cells demonstrated no evidence of CAR T-cell-mediated toxicity, expansion, or persistence, likely due to restricted cell surface FLT3 protein expression in healthy animals. This highlights the limited value of such in vivo studies for safety assessment of the CAR T-cell modality when directed against a target with restricted expression. To complement these studies and directly evaluate the potential toxicities of eliciting T-cell-mediated cytotoxicity against cells with surface expression of FLT3 protein in vivo, data from cynomolgus monkey toxicology studies with 2 bispecific T-cell engager molecules targeting FLT3 were leveraged; findings were consistent with the targeted killing of bone marrow cells expressing cell surface FLT3. Potential AMG 553-induced cytotoxicity was assessed against a wide range of normal human primary cells and cell lines; cytotoxicity was observed against FLT3-positive AML cell lines and a percentage of primary bone marrow CD34+ cells. In conclusion, the nonclinical safety data suggest that AMG 553 can target FLT3 protein on AML cells, whereas only affecting a percentage of normal hematopoietic stem and progenitor cells, supporting clinical development.
During the COVID-19 pandemic, should nurses offer to pray with patients?
Authors: Taylor Elizabeth Johnston
Published: June 2020

Patients hospitalized with COVID-19 are unable to visit with friends and family, and religious patients cannot see personal clergy or even hospital chaplains. These patients may be scared, possibly mechanically ventilated, and dying. In these situations, should their nurse ever initiate an offer of prayer? Weighing the pros and cons of this issue, this discussion will argue that when offered in an ethical, patient-centered manner, nurses offering prayer can be therapeutic for some patients.
Effect of Respiratory Physiological Changes on Optic Nerve Sheath Diameter and Cerebral Oxygen Saturation in Patients With Acute Traumatic Brain Injury
Authors: Balakrishnan Sweatha , Naik Shwetha , Chakrabarti Dhritiman , Konar Subhas , Sriganesh Kamath
Published: June 2020

Background:

Severe traumatic brain injury (TBI) results in raised intracranial pressure (ICP). Ultrasonographic measurement of the optic nerve sheath diameter (ONSD) is a noninvasive method for the assessment of raised ICP. Manipulation of positive end-expiratory pressure (PEEP) and end-tidal carbon dioxide (ETCO2) are often used to optimize ICP and improve oxygenation in TBI patients. This study evaluated the effects of PEEP and ETCO2 on ONSD and regional cerebral oxygen saturation (rScO2) in patients with acute TBI.

Methods:

A total of 14 patients (11 males) aged older than 18 years with acute severe TBI were included in this study. ONSD and rScO2 were assessed before and after changes in PEEP from 5 to 10 cm H2O and in ETCO2 from 40 to 30 mm Hg on both pathologic and nonpathologic sides.

Results:

Increasing PEEP and reducing ETCO2 resulted in changes in ONSD and rScO2 on both pathologic and nonpathologic sides. On the pathologic side, ONSD and rScO2 were highest with a PEEP of 10 cm H2O:ETCO2 40 mm Hg combination and lowest with PEEP of 5 cm H2O:ETCO2 30 mm Hg (ONSD 5.24±0.49 vs. 4.27±0.36 mm, P<0.001; rScO2 70.7±9.91% vs. 66.3±9.75%, P<0.001); both PEEP and ETCO2 had significant effects on ONSD and rScO2 (P<0.001). On the nonpathologic side, ONSD and rScO2 were highest and lowest with PEEP of 10 cm H2O:ETCO2 40 mm Hg and PEEP of 5 cm H2O:ETCO2 30 mm Hg combinations, respectively (ONSD: 4.93±0.46 vs. 4.02±0.40 mm, P<0.001; rScO2: 74.77±8.30% vs. 70.69±8.12%, P<0.001). ETCO2 had a significant effect on rScO2 (P<0.001), but the impact of PEEP on rScO2 was not statistically significant (P=0.05).

Conclusion:

Increasing PEEP resulted in significant increases in ONSD and rScO2, whereas reducing ETCO2 significantly decreased ONSD and rScO2.
Revisiting the Beighton Criteria: Does Ligamentous Laxity Testing Correlate With Shoulder Range of Motion Norms in a North American, Pediatric Population?
Authors: Cahill Sean V. , Sharkey Melinda S. , Carter Cordelia W.
Published: June 2020

Background:

Ligamentous laxity testing using the Beighton score is frequently used as part of the pediatric shoulder examination. However, the relationship between generalized ligamentous laxity (GLL) and shoulder range of motion (ROM) remains unexamined in children, and normative data for these clinical tests have not been well established. In this study, we establish normative data for shoulder range of motion and GLL in a healthy, diverse pediatric population and investigate whether Beighton testing correlates with shoulder ROM in children.

Methods:

Healthy subjects age 2 to 18 years with isolated lower extremity complaints were recruited. Passive shoulder ROM measurements for forward flexion (FF), abduction (ABD), internal rotation (IR), external rotation (ER), and extension (EXT) were obtained using a long-armed goniometer. The Beighton score was obtained, with a positive test defined as ≥5. Descriptive statistics were used to stratify data on the basis of age and sex. Interclass correlation coefficients (ICCs) were calculated. Spearman’s r was calculated to determine correlations between the Beighton score and shoulder ROM. Predictive indices of a positive Beighton test to identify patients with high shoulder mobility (ROM in the top 15 percentile, or 1 SD above the mean) were calculated.

Results:

A total of 202 subjects were enrolled and evaluated. Passive ROM norms by age and sex were determined. Intraclass correlation coefficients for all shoulder ROM measurements were substantial to excellent. Female individuals had greater ROM than age-matched male individuals, but this trend was largely statistically insignificant. Pearson’s correlation between age and shoulder ROM was significant for FF, ABD, EXT, and ER (r=−0.52 to −0.20, P<0.001). Based on a Beighton score of ≥5, the prevalence of GLL was 10% in male and 15% in female individuals. Spearman’s correlation between Beighton score and shoulder ROM was significant for 3 of 5 ROM measurements: FF, ER, and EXT (r=0.30 to 0.39, P<0.001).

Conclusions:

Normative pediatric shoulder ROM and joint laxity data have been established in a healthy, diverse population of children. Beighton testing exhibits only a weak to moderate correlation, despite statistical significance, with shoulder ROM and is poorly predictive for high ROM in children.

Level of Evidence:

Level I— Diagnostic.
Combined Phacoemulsification With Goniosynechialysis Under Ophthalmic Endoscope for Primary Angle-closure Glaucoma After Failed Trabeculectomy
Authors: Nie Li , Fu Lin , Chan Yau Kei , Fang Aiwu , Pan Weihua
Published: June 2020

Precis:

Phacoemulsification with goniosynechialysis under an ophthalmic endoscope (Phaco-OE-GSL) is safe and able to lowering intraocular pressure (IOP) for failed trabeculectomy in primary angle-closure glaucoma with cataract. The larger pupil diameter and younger age are identified as the 2 risk factors for surgical outcome.

Purpose:

To investigate the efficacy and safety of combined Phaco-OE-GSL for primary angle-closure glaucoma with cataract after failed trabeculectomy.

Materials and Methods:

Twenty-five patients (25 eyes) were enrolled in this retrospective study. IOP, best-corrected visual acuity, and number of glaucoma medications at baseline and each postoperative follow-up visit were recorded. Peripheral anterior synechia (PAS) was recorded using gonioscopy. Binary logistic regression was used to analyze the risk factors of surgical failure.

Results:

The mean follow-up duration was 17.9±11.4 months. The mean IOP was significantly lower than the preoperative baseline IOP at all time points (P<0.001). The mean IOP was reduced from 24.4±6.5 mm Hg at baseline to 14.2±3.0 mm Hg at the last follow-up. The mean preoperative number of glaucoma medications was 2.2±1.2, which reduced to 0.9±1.1 at the last follow-up. The complete success rates at 1 year and the last follow-up were 70.6% and 68%, respectively. The total success rates were 96% and 92%, respectively. The most common postoperative complications were IOP spikes (48%) and hyphemas (32%). All eyes had degrees of PAS recurrence, with a range of 96.1±52.5 degrees (30 to 210 degrees) after 4 to 6 months. Larger pupil diameter and younger age were significantly associated with the failure of Phaco-OE-GSL.

Conclusions:

Phaco-OE-GSL is safe and can lower IOP for failed trabeculectomy in PACG with cataract despite the high recurrence rate of PAS.
Drug Eluting Versus Covered Metal Stents in Malignant Biliary Strictures—Is There a Clinical Benefit?
Authors: Mohan Babu P. , Canakis Andrew , Khan Shahab R. , Chandan Saurabh , Ponnada Suresh , McDonough Stephanie , Adler Douglas G.
Published: June 2020

Goals/Background:

Patients with malignant biliary obstruction (MBO) often require transpapillary stenting for symptomatic relief and biliary decompression. Plastic stents and uncovered metal stents are now replaced by covered self-expanding metal stents (SEMS). However, stent occlusion from tumor overgrowth and chronic inflammation continues to be an issue. Drug-eluting stents (DES), through an antitumor paclitaxel membrane, have been used to combat this problem. The aim of this study was to conduct a meta-analysis comparing DES to SEMS in MBO.

Study:

Multiple databases were searched to identify studies that compared the clinical outcomes of SEMS and DES in patients with MBO. Random-effects model was used to calculate the pooled odds ratio and the pooled individual outcomes. Our primary goals were to assess the stent patency and overall survival in days. Secondary outcomes assessed the individual reported adverse events and/or complications.

Results:

Five studies including 348 patients (175 males and 173 females) were included. The pooled odds ratio of stent patency was 1.03 (95% confidence interval: 0.68-1.54, P=0.9) and overall survival was 1.16 (95% confidence interval: 0.63-2.11, P=0.6). The pooled rate of stent patency was 168.3 (95% 140.7-196.4) days for DES and 149.4 (117.6-181.2) days for SEMS. The pooled rate of overall survival was 267.2 (206.2-328.2) days for DES and 218.2 (148.5-287.8) days for SEMS.

Conclusion:

On the basis of this meta-analysis, DES and SEMS seem to demonstrate comparable clinical outcomes in patients with malignant biliary strictures. Reported adverse events and/or complications were comparable as well.
Metastatic NUT Midline Carcinoma Treated With Aggressive Neoadjuvant Chemotherapy, Radiation, and Resection: A Case Report and Review of the Literature
Authors: Sopfe Jenna , Greffe Brian , Treece Amy L.
Published: June 2020

NUT midline carcinoma, characterized by the rearrangement of the nuclear protein in testis (NUTM1) gene, is a rare and aggressive subtype of squamous cell carcinoma. This disease is rarely cured and there have been no reports of cure in patients with distant metastatic disease. In fact, patients typically succumb to NUT midline carcinoma within 6 to 12 months from diagnosis. The authors report on a single patient who presented widely metastatic disease who has now been in remission for 37 months after multimodal therapy with compressed cycles of vincristine, cyclophosphamide, and doxorubicin alternating with ifosfamide and etoposide, high-dose radiation, and postchemotherapy resection.
Human listeners’ perception of behavioural context and core affect dimensions in chimpanzee vocalizations
Authors: Kamiloğlu Roza G. , Slocombe Katie E. , Haun Daniel B. M. , Sauter Disa A.
Published: June 2020

Vocalizations linked to emotional states are partly conserved among phylogenetically related species. This continuity may allow humans to accurately infer affective information from vocalizations produced by chimpanzees. In two pre-registered experiments, we examine human listeners' ability to infer behavioural contexts (e.g. discovering food) and core affect dimensions (arousal and valence) from 155 vocalizations produced by 66 chimpanzees in 10 different positive and negative contexts at high, medium or low arousal levels. In experiment 1, listeners (
n
= 310), categorized the vocalizations in a forced-choice task with 10 response options, and rated arousal and valence. In experiment 2, participants (
n
= 3120) matched vocalizations to production contexts using yes/no response options. The results show that listeners were accurate at matching vocalizations of most contexts in addition to inferring arousal and valence. Judgments were more accurate for negative as compared to positive vocalizations. An acoustic analysis demonstrated that, listeners made use of
brightness
and
duration
cues, and relied on
noisiness
in making context judgements, and
pitch
to infer core affect dimensions. Overall, the results suggest that human listeners can infer affective information from chimpanzee vocalizations beyond core affect, indicating phylogenetic continuity in the mapping of vocalizations to behavioural contexts.
Streptococcal toxic shock syndrome in a patient with community-acquired pneumonia. Impact of rapid diagnostics on patient management
Authors: Bagge Kristian , Pedersen Louise , Lisby Jan Gorm
Published: June 2020

Here we describe a community-acquired pneumonia with

Streptococcus pyogenes

, group A following a common cold caused by human metapneumovirus. The patient, a 58-year-old woman with no prior medical history, developed respiratory failure and multi-organ dysfunction caused by streptococcal toxic shock syndrome. The patient was admitted to the intensive care unit and treated with supportive care. The definitive diagnosis was made by BioFire FilmArray by Biomerieux (multiplex PCR) 12 h before positive blood culture, thus enabling the clinician to add clindamycin and intravenous immunoglobulin to the treatment. The patient was discharged fully recovered after 23 days. Streptococci group A is a rare pathogen of severe pneumonia and rapid diagnostics by syndromic testing, potentially performed in a near patient setting, is crucial for early implementation of targeted antimicrobial treatment.
The stability of HIV-2 Vpx and Vpr proteins is regulated by the presence or absence of zinc-binding sites and poly-proline motifs with distinct roles
Authors: Shimagaki Kazunori , Koga Ryoko , Fujino Haruna , Ahagon Ami , Tateishi Hiroshi , Otsuka Masami , Yamaguchi Yoshihiro , Fujita Mikako
Published: June 2020

The Vpx and Vpr proteins of human immunodeficiency virus type 2 (HIV-2) are important for virus replication. Although these proteins are homologous, Vpx is expressed at much higher levels than Vpr. Previous studies demonstrated that this difference results from the presence of an HHCC zinc-binding site in Vpx that is absent in Vpr. Vpx has another unique region, a poly-proline motif (PPM) of seven consecutive prolines at the C-terminus. Using PPM point mutants of Vpx, this study demonstrated that these seven consecutive prolines are critical for suppressing proteasome degradation of Vpx in the absence of Gag. Both the PPM and the zinc-binding site stabilize Vpx but do so via different mechanisms. PPM and zinc-binding site mutants overexpressed in

Escherichia coli

aggregated readily, indicating that these motifs normally prevent exposure of the hydrophobic region outside the structure. Furthermore, introduction of the zinc-binding site and the PPM into Vpr increased the level of Vpr expression so that it was as high as that of Vpx. Intriguingly, HIV-2 has evolved to express Vpx at high levels and Vpr at low levels based on the presence and absence of these two motifs with distinct roles.