bluuebunny/crossref_metadata_2025 huggingface dataset:
Universal Mismatch Repair Protein Screening in Upper Tract Urothelial Carcinoma
Authors: Gayhart Matthew George , Johnson Nicole , Paul Asit , Quillin John M , Hampton Lance J , Idowu Michael O , Smith Steven Christopher
Published: May 2020

Objectives

Universal screening of upper tract urothelial carcinoma (UTUC) for Lynch syndrome by mismatch repair (MMR) protein immunohistochemistry (IHC) has been recommended by some investigators. Herein, we assess this recommendation retrospectively by simulating its performance on a retrospective, unselected cohort of UTUCs, with comparison to the established setting of colorectal and endometrial adenocarcinoma.

Methods

We assessed for complete loss of MMR protein (MLH1, MSH2, MSH6, and PMS2) IHC in 74 consecutive cases of UTUC and then tabulated clinical and pathologic factors. MMR findings from same-institution colorectal and endometrial adenocarcinomas were tabulated for comparison.

Results

We observed loss of at least one MMR protein in 12% in our UTUC cohort (three MSH2/MSH6, three MSH6 only, one MLH1/PMS2, and two PMS2 only). Of these nine cases (seven males, two females, median age 67 years, five associated with colorectal adenocarcinoma), at least three (4% of the overall cohort) proved to be Lynch syndrome. Overall, MMR loss in UTUC was comparable to colorectal (11%; 50 of 471 cases) and endometrial (12%; 12 of 101 cases) adenocarcinomas.

Conclusions

The rate of MMR loss observed in UTUC was comparable to that in the established setting of colorectal and endometrial adenocarcinomas, supporting universal UTUC screening at our institution and others.
The origin of the giant ground beetleAplothorax burchellion St Helena Island
Authors: Sota Teiji , Hori Michio , Scholtz Clarke , Karagyan Gayane , Liang Hong-Bin , Ikeda Hiroshi , Takami Yasuoki
Published: May 2020

Some highly isolated oceanic islands harbour endemic ground beetles that have lost the ability to fly. Here, we investigated the origin of the possibly extinct flightless giant ground beetle Aplothorax burchelli on St Helena Island in the South Atlantic. Aplothorax burchelli was initially considered to be a member of the subtribe Calosomina (=genus Calosoma) of the subfamily Carabinae (Coleoptera: Carabidae) closely related to the genus Ctenosta (=Calosoma subgenus Ctenosta), but this proposition was questioned due to its unique external and genital morphology. We conducted a phylogenetic analysis of mitogenome sequences using historical specimens of A. burchelli and samples of representative species of Carabinae. Our analysis of 13 protein-coding gene sequences revealed that A. burchelli is definitely a member of Calosomina, most closely related to a species of Ctenosta. Further analysis using NADH dehydrogenase subunit 5 gene sequences from most groups in Calosomina showed that A. burchelli formed a monophyletic group with Ctenosta species from Africa and Madagascar. Our results suggest that the ancestor of A. burchelli, which had the ability to fly, colonized St Helena from Africa after the emergence of the island 14 Mya, and has since undergone evolutionary changes in conjunction with loss of flight.
Subcellular Localization And Formation Of Huntingtin Aggregates Correlates With Symptom Onset And Progression In A Huntington’S Disease Model
Authors: Landles Christian , Milton Rebecca E , Ali Nadira , Flomen Rachel , Flower Michael , Schindler Franziska , Gomez-Paredes Casandra , Bondulich Marie K , Osborne Georgina F , Goodwin Daniel , Salsbury Grace , Benn Caroline L , Sathasivam Kirupa , Smith Edward J , Tabrizi Sarah J , Wanker Erich E , Bates Gillian P
Published: May 2020

Huntington’s disease is caused by the expansion of a CAG repeat within exon 1 of the HTT gene, which is unstable, leading to further expansion, the extent of which is brain region and peripheral tissue specific. The identification of DNA repair genes as genetic modifiers of Huntington’s disease, that were known to abrogate somatic instability in Huntington’s disease mouse models, demonstrated that somatic CAG expansion is central to disease pathogenesis, and that the CAG repeat threshold for pathogenesis in specific brain cells might not be known. We have previously shown that the HTT gene is incompletely spliced generating a small transcript that encodes the highly pathogenic exon 1 HTT protein. The longer the CAG repeat, the more of this toxic fragment is generated, providing a pathogenic consequence for somatic expansion. Here, we have used the R6/2 mouse model to investigate the molecular and behavioural consequences of expressing exon 1 HTT with 90 CAGs, a mutation that causes juvenile Huntington’s disease, compared to R6/2 mice carrying ∼200 CAGs, a repeat expansion of a size rarely found in Huntington’s disease patient’s blood, but which has been detected in post-mortem brains as a consequence of somatic CAG repeat expansion. We show that nuclear aggregation occurred earlier in R6/2(CAG)90 mice and that this correlated with the onset of transcriptional dysregulation. Whereas in R6/2(CAG)200 mice, cytoplasmic aggregates accumulated rapidly and closely tracked with the progression of behavioural phenotypes and with end-stage disease. We find that aggregate species formed in the R6/2(CAG)90 brains have different properties to those in the R6/2(CAG)200 mice. Within the nucleus, they retain a diffuse punctate appearance throughout the course of the disease, can be partially solubilized by detergents and have a greater seeding potential in young mice. In contrast, aggregates from R6/2(CAG)200 brains polymerize into larger structures that appear as inclusion bodies. These data emphasize that a subcellular analysis, using multiple complementary approaches, must be undertaken in order to draw any conclusions about the relationship between HTT aggregation and the onset and progression of disease phenotypes.
Performance of Capsule Endoscopy and Cross-Sectional Techniques in Detecting Small Bowel Lesions in Patients with Crohn’s Disease
Authors: Calabrese Carlo , Diegoli Margherita , Dussias Nikolas , Salice Marco , Rizzello Fernando , Cappelli Alberta , Ricci Claudio , Gionchetti Paolo
Published: May 2020

Background

Crohn’s disease (CD) can be classified according to endoscopic and cross-sectional imaging characteristics. Information regarding disease extent and phenotype may be provided by advanced endoscopic and imaging techniques. In this study, we compare the ability of capsule endoscopy (CE) and cross-sectional imaging techniques (CST) (MRE/Computer Tomography Enteroscopy [CTE]) in detecting small bowel (SB) lesions.

Methods

We retrospectively analyzed 102 patients with a diagnosis of CD who underwent both CE and CST. Only patients with at least a 12-month follow-up after CE were included.

Results

Sensitivity and specificity for the detection of SB lesions were, respectively, 100% and 83.3% for CE, 55.1% and 80% for CTE, and 60% and 82.3% for MRE. CE detected proximal CD lesions in 73% of patients, whereas MRE and CTE detected proximal lesions in 41% and 16% of patients, respectively (P < 0.001). Positive findings on CE led to management changes in all patients, in a median follow-up period of 58.7 months. During the follow-up period, 26.5% of patients underwent surgery. Multivariate analysis revealed that moderate-to-severe disease at CE was independently correlated with surgery (P = 0.03).

Conclusions

CE has a superior sensitivity for detecting CD lesions in the proximal and medium SB compared with CST. In the terminal ileum, MRE and CTE displayed similar performance to CE.
Internalized Orientalism: Toward a Postcolonial Media Theory and De-Westernizing Communication Research from the Global South
Authors: Alahmed Anas M
Published: May 2020

This article applies the concept of internalized orientalism to explain how news representations reflect the power struggles and power relationships within postcolonial nations of the global South through Orientalist discourses. Introducing the concept of internalized orientalism to postcolonial media studies has the potential to de-westernize communication research by depicting the interplays of representations within the South. In this article, I analyze internalized orientalism as a communication theory by studying media representations of the Egyptian revolution in terms of four themes: (a) inability of southern people to rule themselves, (b) religious versus civil state, (c) social conflicts and the patriarchal state, and (d) dehumanization of people and reducing human agency. I argue that internalized orientalism demonstrates how media representations reflect a Western production of knowledge of the global South in the global South, working toward reproducing neocolonial power. At the same time, I argue, internalized orientalism offers a lens for understanding the politics of representations and knowledge production from the South.
Long-term Motor and Cognitive Function in the Children of Women With Inflammatory Bowel Disease
Authors: Friedman Sonia , Nielsen Jan , Jølving Line Riis , Nøhr Ellen A , Nørgård Bente Mertz
Published: May 2020

Introduction

Research on long-term outcomes of children exposed to inflammatory bowel disease [IBD] in utero is lacking. Maternal inflammation, IBD medications, or other factors may increase the risk of developmental disabilities in the offspring.

Methods

We used the Danish National Birth Cohort, an ongoing prospective study that includes 100 419 pregnancies of 92 274 women, in conjunction with the Danish National Registries, to evaluate cognitive and motor development of the children of women with and without IBD. We analysed basic measures of childhood development at 6-month and 18-month interviews with the mother and with validated questionnaires filled out by the parents when the child was 7 years old. We adjusted for multiple confounders, including preterm birth.

Results

At 6 months, we included 484 children of women with IBD and 69 571 unexposed children; at 18 months, 471 exposed and 66 018 unexposed; at 7 years, 391 exposed and 54 356 unexposed. At 18 months, exposed children were significantly less likely to ‘use word-like sounds’ but there was no difference between use of ‘sentences of 2 words’. At 6 and 18 months, there were no other obvious differences in language and motor development. At 7 years, cognitive scores [emotional, conduct, hyperactivity, peer, and social scores] and motor development [gross/fine motor skills and general coordination] were similar between the two groups.

Conclusions

Children exposed to IBD in utero and unexposed children scored similarly on survey-based tools assessing basic measures of neurodevelopment over 7 years. These results are reassuring for current and future parents with IBD.
Aortic root rupture during balloon-expandable transcatheter aortic valve replacement in a patient without recognized risk factors for aortic root rupture: a case report
Authors: Tsuda Masaki , Mizote Isamu , Mukai Takashi , Sakata Yasushi
Published: May 2020

Background

Aortic root rupture is a severe complication of balloon-expandable transcatheter aortic valve replacement (TAVR). Although previous studies have revealed several risk factors for this complication, predicting this complication is occasionally difficult.

Case summary

A 78-year-old male patient underwent TAVR via a transfemoral approach using a 29-mm balloon-expandable valve. No recognized risk factors for aortic root rupture existed in pre-procedural multi-detector computed tomography (MDCT) analysis. However, after the valve deployment, sudden haemodynamic collapse occurred. Transoesophageal echocardiography revealed pericardial effusion, which led to an immediate diagnosis of cardiac tamponade following aortic root rupture. Following pericardial drainage via a subxiphoid approach, the haemodynamics were immediately stabilized. After 10 days of close observation, the patient was discharged on Day 39 without additional problems. He was still alive at the 6-month follow-up without sequelae.

Discussion

Established risk factors for aortic root rupture include >20% area oversizing, bicuspid aortic valve, small annulus (<20 mm), shallow sinus of Valsalva (SOV) compared with the aortic annulus, and massive annular or subannular calcification. Our patient did not have any of the recognized risk factors for aortic root rupture, suggesting the existence of other factors. Pre-procedural MDCT showed a flat calcification orthogonal to the aortic root wall, and post-procedural MDCT revealed that this calcification penetrated the SOV with extravasation. Thus, we suggest that a flat calcification orthogonal to the aortic root wall might be an additional risk factor for aortic root rupture.
Repetitive out of hospital cardiac arrests following pregnancy: a case report of an unfortunate presentation of mitral annular disjunction
Authors: Van Berendoncks An , McGhie Jackie , Heidbuchel Hein , Roos-Hesselink Jolien W
Published: May 2020

Background

Mitral annular disjunction (MAD) is an under-recognized cause of arrhythmic sudden cardiac death, especially in young women. The relation between MAD and the occurrence of arrhythmia during pregnancy has not yet been explored. We would like to stress the importance of careful echocardiographic examination and the vulnerable peripartum period.

Case summary

A 29-year-old woman survived an out of hospital cardiac arrest 4 months after delivery of her first child. The diagnosis was not clear and an implantable cardioverter-defibrillator (ICD) as secondary prevention was implanted. Her second pregnancy and delivery were uneventful. The 12-lead electrocardiogram demonstrated sinus rhythm with right bundle branch block, ventricular extra systoles (premature ventricular contractions), and a right superior axis, i.e. origin in the inferolateral basal left ventricle. Transthoracic 2D echocardiography showed myxomatous mitral valve disease with moderate mitral valve insufficiency with normal left and right heart dimensions and function. However, 4 weeks after delivery she experienced a sudden syncope at home. Implantable cardioverter-defibrillator reading revealed primary ventricular fibrillation, induced by a ventricular premature beat (VPB), terminated with a successful ICD shock. A frame-by-frame echocardiographic analysis of the mitral valve using biplane echocardiographic analysis allowed diagnosis of MAD with detachment of the root of the annulus from the posterolateral ventricular myocardium during systole.

Conclusion

Mitral annular disjunction is an under-recognized cause of arrhythmic sudden cardiac death. Biplane echocardiographic analysis of the mitral annulus can identify MAD and as such may help for risk stratification and sudden cardiac death prevention. Careful follow-up is necessary especially during pregnancy and the postpartum period.
The PKGIα/VASP pathway is involved in insulin- and high glucose-dependent regulation of albumin permeability in cultured rat podocytes
Authors: Rachubik Patrycja , Szrejder Maria , Audzeyenka Irena , Rogacka Dorota , Rychłowski Michał , Angielski Stefan , Piwkowska Agnieszka
Published: May 2020

Podocytes, the principal component of the glomerular filtration barrier, regulate glomerular permeability to albumin via their contractile properties. Both insulin- and high glucose (HG)-dependent activation of protein kinase G type Iα (PKGIα) cause reorganization of the actin cytoskeleton and podocyte disruption. Vasodilator-stimulated phosphoprotein (VASP) is a substrate for PKGIα and involved in the regulation of actin cytoskeleton dynamics. We investigated the role of the PKGIα/VASP pathway in the regulation of podocyte permeability to albumin. We evaluated changes in high insulin- and/or HG-induced transepithelial albumin flux in cultured rat podocyte monolayers. Expression of PKGIα and downstream proteins was confirmed by western blot and immunofluorescence. We demonstrate that insulin and HG induce changes in the podocyte contractile apparatus via PKGIα-dependent regulation of the VASP phosphorylation state, increase VASP colocalization with PKGIα, and alter the subcellular localization of these proteins in podocytes. Moreover, VASP was implicated in the insulin- and HG-dependent dynamic remodelling of the actin cytoskeleton and, consequently, increased podocyte permeability to albumin under hyperinsulinaemic and hyperglycaemic conditions. These results indicate that insulin- and HG-dependent regulation of albumin permeability is mediated by the PKGIα/VASP pathway in cultured rat podocytes. This molecular mechanism may explain podocytopathy and albuminuria in diabetes.
Inter-Population Similarities and Differences in Predation Efficiency of a Mosquito Natural Enemy
Authors: Cuthbert Ross N , Dalu Tatenda , Wasserman Ryan J , Weyl Olaf L F , Froneman P William , Callaghan Amanda , Dick Jaimie T A
Published: May 2020

Predation is a critical factor that mediates population stability, community structure, and ecosystem function. Predatory natural enemies can contribute to the regulation of disease vector groups such as mosquitoes, particularly where they naturally co-occur across landscapes. However, we must understand inter-population variation in predatory efficiency if we are to enhance vector control. The present study thus employs a functional response (FR; resource use under different densities) approach to quantify and compare predatory interaction strengths among six populations of a predatory temporary pond specialist copepod, Lovenula raynerae, from the Eastern Cape of South Africa preying on second instar Culex pipiens complex mosquito larvae. All individuals from the sampled populations were predatory and drove significant mortality through per capita predation rates of 0.75–1.10 mosquitoes/h at maximum densities over a 5-h feeding time. Individuals from all copepod populations exhibited Type II FRs with no significant differences in attack rates. On the other hand, there were significant differences in handling times, and therefore also maximum feeding rates (maximum experimental prey density: 32), suggesting possible genetic differences among populations that influenced predation. Owing to a widespread distribution in arid landscapes, we propose that predatory calanoid copepods such as L. raynerae play a key regulatory role at the landscape scale in the control of disease vector mosquito populations. We propose that these ecosystems and their specialist biota should thus be conserved and enhanced (e.g., via selective breeding) owing to the ecosystem services they provide in the context of public health.
Identification of functionally distinct and interacting cancer cell subpopulations from glioblastoma with intratumoral genetic heterogeneity
Authors: Guo Min , van Vliet Marjolein , Zhao Jian , de Ståhl Teresita Díaz , Lindström Mikael S , Cheng Huaitao , Heller Susanne , Nistér Monica , Hägerstrand Daniel
Published: May 2020

Background

Glioblastomas display a high level of intratumoral heterogeneity with regard to both genetic and histological features. Within single tumors, subclones have been shown to communicate with each other to affect overall tumor growth. The aim of this study was to broaden the understanding of interclonal communication in glioblastoma.

Methods

We have used the U-343 model, consisting of U-343 MG, U-343 MGa, U-343 MGa 31L, and U-343 MGa Cl2:6, a set of distinct glioblastoma cell lines that have been derived from the same tumor. We characterized these with regard to temozolomide sensitivity, protein secretome, gene expression, DNA copy number, and cancer cell phenotypic traits. Furthermore, we performed coculture and conditioned media-based experiments to model cell-to-cell signaling in a setting of intratumoral heterogeneity.

Results

Temozolomide treatment of a coculture composed of all 4 U-343 cell lines presents a tumor relapse model where the least sensitive population, U-343 MGa 31L, outlives the others. Interestingly, the U-343 cell lines were shown to have distinct gene expression signatures and phenotypes although they were derived from a single tumor. The DNA copy number analysis revealed both common and unique alterations, indicating the evolutionary relationship between the cells. Moreover, these cells were found to communicate and affect each other’s proliferation, both via contact-dependent and -independent interactions, where NOTCH1, TGFBI, and ADAMTS1 signaling effects were involved, respectively.

Conclusions

These results provide insight into how complex the signaling events may prove to be in a setting of intratumoral heterogeneity in glioblastoma and provide a map for future studies.
Semantic Deflationism and Meta-Ontological Deflationism
Authors: Marschall Benjamin , Schindler Thomas
Published: May 2020

Deflationary positions have been defended in many areas of philosophy. Most prominent are semantic deflationism about truth and reference, and meta-ontological deflationism, according to which existence has no deep nature and the standard neo-Quinean approach to ontology is misguided. Although both kinds of views have generated much discussion, surprisingly little attention has been paid to the question of how they relate to each other. Are they independent, is it advisable to hold them all at once, or do they even entail each other? One exception is Amie Thomasson, who has argued that semantic deflationism actually entails meta-ontological deflationism. This is unexpected, since semantic deflationism is usually regarded as much less controversial than meta-ontological deflationism. In our paper, we will argue that Thomasson’s argument fails though, and that the connection between the views is in fact weaker than she makes them out to be.
Psychological and self-management support for people with vasculitis or connective tissue diseases: UK health professionals’ perspectives
Authors: Robson Joanna C , Shepherd Michael , Harper Lorraine , Ndosi Mwidimi , Austin Keziah , Flurey Caroline , Logan Sarah , Dures Emma
Published: May 2020

Objectives

CTD and systemic vasculitis impact on health-related quality of life. Treatment can be complex, involving multiple medical specialities. The aim of this study was to investigate psychological and self-management support for patients in secondary care.

Methods

An online survey of health professionals in the UK, including 45 multiple-choice and free-text questions, was analysed descriptively. Free-text survey responses were analysed thematically to identify health professionals’ perceptions of best practice and unmet needs.

Results

The online survey included 120 health professionals (34% specialist nurses, 51% doctors and 12% allied health professionals), predominantly working in rheumatology (52.9%) and nephrology (21.5%) departments. Access to self-management programmes or clinics for people with CTD or vasculitis was available in 23% of rheumatology and 8% of nephrology departments. In response to ‘How well is your team providing self-management support to people with CTD or vasculitis?’, 38% of respondents reported ‘not very well’ or ‘not well at all’. Direct access to psychological support was available in 76.9% of nephrology and 32.8% of rheumatology departments. More than 80% of respondents would like additional training. Key themes from the qualitative data (free-text survey responses) included the importance of: dedicated psychological support and self-management programmes for people with CTD and vasculitis, a whole-team approach (specialist teams empowering people to manage their own care), staff training (e.g. brief psychological interventions) and signposting to resources, including patient charities.

Conclusion

People with CTD and vasculitis have complex needs, and improvements in self-management and psychological support are required in UK rheumatology and nephrology departments.
Evaluation criteria versus firm characteristics as determinants of public R&D funding
Authors: Thomas Falk Martin , Svensson Roger
Published: May 2020

This study provides new empirical evidence regarding the relevance of evaluation criteria and firm characteristics for public R&D funding decisions. The database used contains both accepted and rejected R&D project proposals, project evaluation scores, and several firm characteristics. The probit estimations show that proposals with high scores on innovative content, spillover, and knowledge gain are significantly more likely to be approved and that most firm-level characteristics are not significant, except for firm size. For example, good or very good assessments of innovative content raise the acceptance probability by between 18 and 37 percentage points, respectively. Small firms are more likely to receive a grant.
0001 Activation of Nociceptin/Orphanin-FQ Peptide (NOP) Receptors Produces an Increase in Non-REM Sleep in Rats and Constitutes a Novel and Attractive Target for the Treatment of Insomnia
Authors: Whiteside G T , Hummel M , Knappenberger T , Hiroyama S , Itoh T , Takai N , Kyle D J
Published: May 2020

Introduction

Treatments for insomnia have targeted GABA, histamine, serotonin, melatonin and orexin receptors. The nociceptin/orphanin-FQ peptide (NOP) receptor is widely expressed in the nervous system. High doses of NOP agonists administered systemically or locally into the CNS can result in sedation, however, the utility of targeting this receptor to treat insomnia has not been fully described.

Methods

V117957 is a recently described investigational oral, potent and selective NOP receptor partial agonist. We determined the brain Kp in whole brain and multiple sub-regions (50mg/kg) and receptor occupancy in the hypothalamus (30, 300mg/kg) via in vivo displacement using [3H]-NOP-1A. EEG/EMG were determined in rats chronically implanted with electrodes (cortex and dorsal neck muscle) and recorded via telemetry following dosing (3, 30, 300mg/kg); sleep stage was determined from visual analysis of EEG level. Sleep parameters were also assessed in NOP receptor knock-out rats (300mg/kg). The side-effect profile for V117957 was determined by functional observation battery, whole-body plethysmography, Morris water maze (MWM) (up to 600mg/kg) and conditioned place preference (CPP) assay (up to 300mg/kg).

Results

V117957 displayed limited distribution into the CNS but achieved a high level of receptor occupancy (75% at 30mg/kg). Administration of V117957 produced dose-dependent and statistically significant increases in non-REM sleep with a minimally efficacious dose of 30mg/kg; a coincident dose-dependent and statistically significant decrease in wakefulness and a non-dose-dependent effect on REM sleep occurred. These changes were not seen in knock-out animals demonstrating effects are via NOP receptors. At doses higher than those that increased non-REM sleep, V117957 had no effects in a functional observational battery, did not affect escape latency in MWM or produce CPP; additionally, V117957 did not affect respiratory parameters.

Conclusion

We conclude that activation of NOP receptors decreases wakefulness and increases non-REM sleep in rats with an improved preclinical profile compared to historical profiles of current treatments and, therefore, may represent a novel and attractive target for the treatment of insomnia.

Support

Funded by Shionogi and Imbrium Therapeutics, a subsidiary of Purdue Pharma L.P.
0009 Anti-Streptococcal Antibodies in Chinese Patients with Type -1 Narcolepsy
Authors: Ding Q , Li J , Xiao F , Zhang C , Dong X , Han F
Published: May 2020

Introduction

Narcolepsy type 1 (NT1) is considered to be an autoimmune disease, and streptococcal infection may be an environmental trigger. However, previous studies from Asian narcolepsy patients did not reveal elevated anti-streptolysin O [ASO]. The aim is to investigate whether large sample Chinese patients with NT1 have an increase in antistreptococcal antibody titers.

Methods

A total of 214 narcolepsy patients and 360 healthy controls were recruited. All patients were DQB1*0602 positive with clear-cut cataplexy or had low CSF hypocretin-1. Participants were tested for ASO and anti DNAse B [ADB]. These patients were divided into five groups according to disease duration, including 29 patients less than 3 months; 25 from 3 months to 1 year; 40 from 1 to 3 years; 61 from 3 to 10 years and 59 patients over 10 years. Comparison was also made between children and adults with age matched controls, respectively.

Results

There were no significant differences between patients and healthy controls in regard to both ASO ≥ 200 IU (19.2% vs. 16.9%, p = 0.50) and ADB≥480IU (9.8% vs. 10.3%, p = 0.86). For children narcolepsy patients, ASO positive rates(19.8% vs. 18%, p = 0.68) and ADB positive rates(10.4% vs. 12%, p = 0.72) had no differences compared to age matched controls. And no difference was observed in adult narcolepsy patients either, with ASO positive rates (18.5% vs. 13.8%, p = 0.39) and ADB positive rates (9.3% vs. 5.3%, p = 0.42) compared to age matched controls, respectively. ASO (ADB) positive rates had no significant differences among different disease duration groups(p= 0.55, 0.9).

Conclusion

It is indicated that positive rates of ASO and ADB were not significantly different between Chinese patients with NT1 and healthy controls, including recent onset cases and children.

Support

The study was supported by the National Natural Science Foundation of China (No. 81420108002 and NO. 81570083)
0013 Mobile Device Use in Bed and Relationships to Work Productivity: Impact of Anxiety
Authors: Gozar A , Seixas A , Hale L , Branas C , Barrett M , Killgore W D , Wills C C , Grandner M A
Published: May 2020

Introduction

Mobile phone use at night is associated with worse sleep quality. It may also be associated with daytime productivity, possibly via anxiety.

Methods

Data were obtained from the Sleep and Healthy Activity, Diet, Environment, and Socialization (SHADES) study, including N=1007 adults age 22–60. Mobile device use in bed was assessed as the frequency that participants reported: a device in the bedroom, use of the device in bed, texting, emails, internet browsing, calls, and/or social networking in bed, being woken up by the device in a planned (alarm) or unplanned (alert/call/message) way, and checking the phone at night. Each of these were coded as “never,” “rarely,” or “often.” Work productivity was assessed with the Well-Being Assessment of Productivity (WBA-P; scores 0–22 measure productivity loss). Regressions with WBA-P score as outcome and mobile phone variables as predictors were adjusted for age, sex, race/ethnicity, education, and income level. Post-hoc analyses included GAD7 score to examine the mediating role of anxiety.

Results

The presence of a device was not associated with productivity loss, but frequent use (“often”) was (B=1.26,p=0.01). Increased productivity loss was also seen in those who frequently (“often”) sent texts (B=1.20,p=0.008), browsed internet (B=1.14,p=0.01), emailed (B=2.09,p<0.0005), called (B=1.42,p=0.004), and used social media (B=1.26,p=0.004). Productivity loss was associated with being woken by a call/alert “rarely” (B=1.20,p=0.001) or “often” (B=1.72,p=0.005), but not by alarm. Checking the phone at night “rarely” (B=0.89,p=0.01) and “often” (B=1.73,p<0.0005) were also associated with productivity loss. When anxiety was entered into the model, all relationships except those with frequent emails and calls in bed became nonsignificant.

Conclusion

Anxiety may be the underlying cause for both increased mobile phone usage and reduced productivity. Reducing anxiety levels may indirectly aid in decreasing nighttime mobile phone use and increasing daytime productivity.

Support

The SHADES study was funded by R21ES022931

Dr. Grandner is supported by R01MD011600
0015 Manipulating Body Temperature: Effects on Sleep in Postmenopausal Women
Authors: Reid K J , Kräuchi K , Grimaldi D , Sbarboro J , Attarian H , Zee P C
Published: May 2020

Introduction

A decline in sleep quality and reduction in slow wave sleep (SWS) and slow wave activity (SWA) are common in older adults. Prior studies have shown that manipulating body temperature during sleep can increase SWS/SWA. The aim of this study was to determine the effects of manipulation of body temperatures during sleep, using a high heat capacity mattress, on SWS/SWA and heart rate variability in post-menopausal women.

Methods

Twenty-four healthy postmenopausal women between 40–75 years of age (mean age 62.4 ± 8.2 years, mean BMI 25.4 ± 3.5 kg/m2) were randomized in a single-blind, counterbalanced, cross-over manner to sleep on either a high heat capacity mattress (HHCM) or a low heat capacity mattress(LHCM) a week apart. Sleep was recorded using polysomnography during an 8-hour sleep opportunity. Core and peripheral temperatures were recorded using Equivital and ibutton respectively.

Results

In comparison to the LHCM, sleep on HHCM exhibited a selective increase in SWS (average increase in Stage N3 of 9.6 minutes (2.1%), p = 0.04) and in slow oscillatory activity (0.5-1Hz) in the first NREM/REM cycle (p=0.04). In addition, the HHCM induced a greater reduction in core body temperature (p=0.002), and delayed the increase in mattress surface temperature (maximal difference LHCM-HHCM: 4.66±0.17°C). Average heart rate was 2.7 beats/minute lower across the night on the HHCM compared to the LHCM (p=0.001).

Conclusion

The results of this study indicate that manipulation of body temperature during sleep may be a useful approach to enhance SWS sleep and cardiovascular function in postmenopausal women.

Support

Technogel
0036 Inconsistent Bedtimes Associated with Unhealthier Body Size in Older Adults
Authors: Zendels P , Gaultney J
Published: May 2020

Introduction

A variety of sleep related variables have been shown to impact measures of health, including duration of sleep, consistency of sleep, quality of sleep, and sleep disorders. These can impact respiratory health, metabolic health, immune function, and more. Older adults have been shown to have different sleep schedules, with mostly consistent weeknight and weekend bedtimes and more opportunities to nap. The study investigated which aspects of sleep best predicted body size (averaged standardized body mass index and percent body fat indices).

Methods

A sample of 304 older adults (55+) participated in surveys and health measures in an urban area in the southeastern United States. Survey data collected were reports of sleep during the last month, including duration at night, nap duration, measures of quality, typical weeknight and weekend bedtime, and reports of possible sleep disorders. Physiological measures, including height, weight, BMI, body fat percentage, blood sugars, blood fats, and fitness tests were conducted. Sleep data were weighted ((5*weeknight+2*weekend)/7) across the week. A hierarchical multiple regression model was run with a standardized average of BMI and body fat percentage with multiple sleep variables as a predictor, controlling for age and socioeconomic status.

Results

After controlling for age and socioeconomic status (SES), symptoms of obstructive sleep apnea, night sleep duration, nap duration, difficulty initiating and maintaining sleep, sleep midpoint, duration inconsistencies and midpoint inconsistences were added to the regression. SES and duration inconsistencies were significant predictors, explaining 16% of the variance in body size.

Conclusion

Inconsistent bedtimes may be associated with larger body size. Encouraging older adults to have consistent sleep schedules could help preserve health as they age. This may also reduce rates of disorders like obstructive sleep apnea, which are associated with higher BMI, and help promote better overall sleep quality and health. However, these older adults reported fairly consistent sleep midpoint, limiting interpretation of this variable.

Support

Psychological Sciences department funding
0045 Biobehavioral Markers for Sleep/Wake Disturbance and Fatigue in Young Childhood Brain Tumor Survivors
Authors: Johnson A H , Bashore L , Hines A , Aufricht J , Smith A M , Pearson H
Published: May 2020

Introduction

Survivors of childhood and adolescent brain tumors and subsequent treatment may experience many neurological processes involving the forebrain, brainstem, and hypothalamus as well as the symptom cluster of stress, sleep, and fatigue. As a result, the impact of brain tumor treatment (chemotherapy/biotherapy, radiotherapy, and surgery) may have lasting biobehavioral effects. Description of symptoms during early survivorship is not always evident in the literature.

Methods

Convenience sampling and the following inclusion criteria were utilized: brain tumor survivors ages 8–17 years; ≥6 months, <6 years from completion of treatment; disease free or stable disease. Participants completed polysomnography (PSG) followed by a multiple sleep latency test (MSLT), and subjective measures of sleep, fatigue, stress, and pubertal status. Collection of salivary biomarkers for stress (cortisol) and sleep (melatonin) was completed the evening of and morning after the PSG.

Results

Analysis of the first 12 participants (5 males; 3 Hispanic/Latino; average age 14 years; 9–72 months post treatment) revealed mean (minutes) total sleep time (TST) 442, sleep latency (SL) 42 and waking (WASO) 88; sleep efficiency (SE) mean 83%, There were large magnitude correlations between several variables of interest, notably PM Cortisol with fatigue, TST (r= .472; -.453); AM Cortisol with SL (r=.479); AM Melatonin with SE, SL, WASO (r= -.459; .692; .458). Average AM melatonin level (26.6 pg/dl) was higher than PM (6.66 pg/dl). Seven participants were diagnosed with clinical sleep disorders, including one with narcolepsy and two with hypersomnia.

Conclusion

During early survivorship after pediatric brain tumor treatment, survivors may be at high risk for sleep/wake disturbance (SWD). Morning melatonin and biomarker correlations with sleep and fatigue in this sample warrant further exploration and may be related to first night effect versus circadian rhythm differences or clinical sleep disorder. Recommendations for future practice include developmentally matched protocols and routine screening of biobehavioral markers to assess risk for stress, SWD, and fatigue.

Support

1. Center for Oncology Education and Research Harris College of Nursing & Health Sciences Texas Christian University 2. Neuro-Oncology Program Hematology/Oncology Center Cook Children’s Health Care System 3. Nursing Research and Evidence-Based Practice James A. “Buddy” Davidson Endowed Fund
0046 Diffusion Tensor Imaging Evidence of Hypothalamic Injury in Traumatic Brain Injury Warfighters with Sleep Dysfunction
Authors: Werner K , Gerstenslager B , Yeh P , Srikanchana R , Kenney K , Ollinger J
Published: May 2020

Introduction

While sleep disorders occur in 40–70% of chronic traumatic brain injury (TBI) patients, the pathophysiology remains unknown. Increasingly, DTI has been used to evaluate gray matter structures, but no prior studies have evaluated hypothalamic regions in TBI. We hypothesized that TBI patients with poor sleep quality by questionnaire and/or polysomnography (PSG) may have structural injury to hypothalamic sleep circuitry and that this may be detectable by diffusion magnetic resonance imaging (dMRI). We examined diffusion tensor parameters in warfighters using dMRI within the hypothalamus of poor sleepers and compared them to good sleepers.

Methods

A retrospective review of 92 warfighters with blast TBI and loss of consciousness included demographics, structural MRI, dMRI, PSG and Pittsburgh Sleep Quality Index (PSQI) questionnaire. Acquisition of diffusion-weighted and structural data was performed with three Tesla MRI. Using the California Institute of Technology probabilistic high-resolution in vivo atlas as a prior, the hypothalamic nuclei were segmented by applying diffeomorphic registration of T1- and T2-weighted structural images and mapped to dMRI space.

Results

TBI patients within the lowest quartile of hypothalamic fractional anisotropy (FA) measures demonstrated decreased total sleep time (320 +/- 52 minutes vs. 382 +/- 19, p=0.006) on PSG and had more sleep complaints on PSQI (p=0.029) compared to those with the highest quartile of FA measures. There was no difference in BMI, age or AHI among the quartiles. Radial, mean and axial diffusivity quartiles did not carry significant differences in TST or PSQI. Linear models did not show significant correlation between any imaging parameter and sleep quality measures.

Conclusion

Our results reveal microstructural differences in the hypothalami of military TBI patients that may be related to clinical sleep dysfunction. Biomarkers of sleep circuitry damage may further our understanding of sleep dysfunction after TBI. Lack of correlations in linear models may be a reflection of the small sample size or a complex interaction, and removal of outliers did not change our results. Larger longitudinal studies may help clarify the association between hypothalamic and brainstem circuitry structure after TBI and sleep dysfunction.

Support

This work was supported by a grant 130132 from USAMRMC.
0051 Respiratory Cycle-Related EEG Changes (RCREC) Predict Incidence and Recurrence of Cardiovascular Disease
Authors: Tsimpanouli M , Chervin R D , Gliske S V
Published: May 2020

Introduction

Sleep-disordered breathing (SDB) is a common sleep disturbance and is associated with both incident and recurrent cardiovascular disease (CVD). Respiratory Cycle-Related EEG Changes (RCREC), an SDB biomarker, are thought to reflect inspiratory microarousals and are based on quantitative analysis of sleep EEG and breathing. The objective of this study was to assess whether RCREC may predict CVD incidence or recurrence in a large cohort of adults. The RCREC for several frequency bands have been previously shown to predict either higher or lower all-cause mortality in the same cohort.

Methods

Data were obtained from the Sleep Heart Health Study (SHHS), a multicenter longitudinal study that included polysomnograms in middle-aged to older adults. Information about CVD events was collected at baseline and for up to 16 years later. The RCREC values at baseline were computed in the delta, theta, alpha, sigma, beta, and gamma frequency bands during scored epochs of sleep. Cox Proportional Hazard models, were used to assess the relation of each RCREC frequency band and incidence or recurrence of CVD. These models were stratified by sex and adjusted for body-mass index, age, race, smoking status, diabetic status, hypertensive status, HDL cholesterol, LDL cholesterol, and the apnea-hypopnea index (AHI).

Results

There were 3,032 adults with sufficient data quality (mean age at baseline 62±11(SD) years, 58% female). Among 2,500 adults with no reported prior CVD history at baseline, the adjusted odds ratios (95% CI) for delta RCREC 0.948(0.920–0.977), theta RCREC 0.938(0.895–0.984), and alpha RCREC 0.946(0.902–0.993) separately suggested associations with lower CVD incidence, whereas gamma RCREC 1.017(1.001–1.032) predicted a marginal increase. Among 532 adults having prior CVD history at baseline, delta RCREC 0.958(0.927–0.989) and sigma RCREC 0.931(0.895–0.969) separately predicted decreased CVD recurrence. The apnea-hypopnea index (AHI) was not similarly predictive in any model.

Conclusion

The RCREC for several frequency bands, in contrast to AHI, may predict CVD incidence and recurrence. The directionality of the association was surprising and merits further exploration.

Support

NIH:NCATS-TL1-TR-002242, BD2K-K01-ES-026839, HL105999
0056 Identification of a Stable Human Metabolomics-Based Biomarker of Insufficient Sleep and its Association with Cognitive Performance
Authors: Depner C M , Reisdorph N , Wright K
Published: May 2020

Introduction

There are numerous potential benefits of developing objective biomarkers of insufficient sleep including providing screening and diagnostic tools, increasing our understanding of poor sleep health, and supporting sleep-based countermeasures. We analyzed plasma metabolites in humans during two separate occasions of experimental sleep restriction to identify stable biomarkers of insufficient sleep, and assessed the association of these biomarkers with cognitive performance.

Methods

12 healthy adults (6M/6F), aged 24±5y (mean±SD), completed two 18-day protocols separated by 10 days. For each 18-day protocol, participants maintained habitual 9h sleep schedules for two weeks at home, and then completed 4-day laboratory visits with sleep opportunities of: 9h on night 1, 5h on nights 2 and 3, and recovery sleep on night 4. Energy balanced diets were provided 2 days before and throughout laboratory visits. Blood was collected every 2h during scheduled wakefulness on days 1–2 (baseline) and days 3–4 (insufficient sleep), and was analyzed by untargeted liquid chromatography/mass-spectrometry. Sustained attention was assessed every 2 h during scheduled wakefulness with the Psychomotor Vigilance Test (PVT).

Results

After filtering, we detected 6,822 metabolites. Elastic-net regression identified 21 metabolites consistently altered by insufficient sleep in both 18-day protocols. We developed a logistic regression-based biomarker fingerprint of insufficient sleep using 11 of these 21 metabolites with consistent responses to insufficient sleep. This biomarker fingerprint has 74.4% accuracy and 0.822 (0.782–0.858; 95%CI) area under the receiver operator curve. Median reaction time was slower (P<0.05) during insufficient sleep versus baseline. Mediation analyses show our biomarker fingerprint accounts for ~6% of the slower reaction time.

Conclusion

We identified a plasma metabolomics-based biomarker of insufficient sleep with “good” performance. However, this biomarker only accounts for ~6% of reduced PVT performance during insufficient sleep. Our findings suggest that specific biomarkers for insufficient sleep versus cognitive deficits associated with insufficient sleep may be required.

Support

This work was supported by NIH R01HL132150, NIH K01HL145099, NIH F32DK111161, NIH/NCATS Colorado CTSA Grant UL1TR002535, Sleep Research Society Foundation 011-JP-16, and the University of Colorado Boulder Undergraduate Research Opportunities Grant.
0059 Disruption of Circadian Clock Proteins in Obstructive Sleep Apnea Patients
Authors: Gabryelska A , Sochal M , Bialasiewicz P
Published: May 2020

Introduction

Circadian clocks are endogenous coordinators of 24-hour rhythm of behavioral and molecular processes in living organism. They are composed of set of genes, which function as activators - CLOCK and BMAL1, which through binding to regulatory elements containing E-boxes activate transcription of repressor proteins Period (PER1) and cryptochrome (CRY1). The aim of the study was to assess: CLOCK, BMAL1, PER1 and CRY1 in obstructive sleep apnea (OSA) patients.

Methods

The study included 20 individuals, who underwent PSG and based on apnea-hypopnea index (AHI) were divided into severe OSA group (n=10; AHI30; 90% male) and healthy control (n=10; AHI<5; 70% male). All participants had their peripheral blood collected in the evening (9:00-10:00 pm) before and in the morning (6:00-7:00 am) after the PSG. CLOCK, BMAL1, CRY1 and PER1 protein concertation measurements were performed using ELISA.

Results

Increased level of following proteins was observed in OSA group: evening CLOCK (p=0.037), morning CLOCK (p=0.019), morning BMAL1 (p=0.0.16), evening PER1 (p=0.004), morning PER1 (p=0.029) and evening CRY1 (p=0.035). Yet, no significant difference was found between morning and evening level of any of the proteins in OSA and control group. Additionally, morning level of activator proteins CLOCK and BMAL1 had positive correlation with AHI (p=0.022, R=0.510 and p=0.010, R=0.560, respectively) and desaturation index (p=0.209, R=0.487 and p=0.009, R=0.570, respectively), while for repressor proteins PER1 and CRY1 significant correlations were found with desaturation index in the evening (p=0.025, R=0.500 and p=0.048, R=0.448, respectively), AHI in REM stage (p=0.009, R=0.569 and p=0.027, R=0.495, respectively) and AHI (for PER1 only p=0.014, R=0.540).

Conclusion

OSA patients have increased level of circadian clock proteins that corelates with severity of the disease. Further research is needed into the disruption of circadian clock should in OSA patients and possible effect of OSA treatment on concentrations of these proteins should be investigated.

Support

The study was financed by Polish National Centre Grant no. 2018/31/N/NZ5/03931.