bluuebunny/crossref_metadata_2025 huggingface dataset:
Age Differences in COVID-19 Risk Perceptions and Mental Health: Evidence From a National U.S. Survey Conducted in March 2020
Authors: Bruine de Bruin Wändi
Published: May 2020

Objectives

Theories of aging posit that older adult age is associated with less negative emotions, but few studies have examined age differences at times of novel challenges. As COVID-19 spread in the United States, this study therefore aimed to examine age differences in risk perceptions, anxiety, and depression.

Method

In March 2020, a nationally representative address-based sample of 6,666 U.S. adults assessed their perceived risk of getting COVID-19, dying if getting it, getting quarantined, losing their job (if currently working), and running out of money. They completed a mental health assessment for anxiety and depression. Demographic variables and precrisis depression diagnosis had previously been reported.

Results

In regression analyses controlling for demographic variables and survey date, older adult age was associated with perceiving larger risks of dying if getting COVID-19, but with perceiving less risk of getting COVID-19, getting quarantined, or running out of money, as well as less depression and anxiety. Findings held after additionally controlling for precrisis reports of depression diagnosis.

Discussion

With the exception of perceived infection-fatality risk, U.S. adults who were relatively older appeared to have a more optimistic outlook and better mental health during the early stages of the pandemic. Interventions may be needed to help people of all ages maintain realistic perceptions of the risks, while also managing depression and anxiety during the COVID-19 crisis. Implications for risk communication and mental health interventions are discussed.
What are the barriers to implementing national antimicrobial resistance action plans? A novel mixed-methods policy analysis in Pakistan
Authors: Khan Mishal S , Durrance-Bagale Anna , Mateus Ana , Sultana Zia , Hasan Rumina , Hanefeld Johanna
Published: May 2020

Despite political commitment to address antimicrobial resistance (AMR), countries are facing challenges to implementing policies to reduce inappropriate use of antibiotics. Critical factors to the success of policy implementation in low- and middle-income countries (LMIC), such as capacity for enforcement, contestation by influential stakeholders and financial interests, have been insufficiently considered. Using Pakistan as a case study representing a populous country with extremely high antibiotic usage, we identified 195 actors who affect policies on antibiotic use in humans and animals through a snowballing process and interviewed 48 of these who were nominated as most influential. We used a novel card game-based methodology to investigate policy actors’ support for implementation of different regulatory approaches addressing actions of frontline healthcare providers and antibiotic producers across the One Health spectrum. We found that there was only widespread support for implementing hard regulations (prohibiting certain actions) against antibiotic suppliers with little power—such as unqualified/informal healthcare providers and animal feed producers—but not to target more powerful groups such as doctors, farmers and pharmaceutical companies. Policy actors had limited knowledge to develop implementation plans to address inappropriate use of antibiotics in animals, even though this was recognized as a critical driver of AMR. Our results indicate that local political and economic dynamics may be more salient to policy actors influencing implementation of AMR national action plans than solutions presented in global guidelines that rely on implementation of hard regulations. This highlights a disconnect between AMR action plans and the local contexts where implementation takes place. Thus if the global strategies to tackle AMR are to become implementable policies in LMIC, they will need greater appreciation of the power dynamics and systemic constraints that relate to many of the strategies proposed.
On the Minkowski Formula for Hypersurfaces in Complex Space Forms
Authors: Martino Vittorio , Tralli Giulio
Published: May 2020

In this paper, we discuss various Minkowski-type formulas for real hypersurfaces in complex space forms. In particular, we investigate the formulas suggested by the natural splitting of the tangent space. In this direction, our main result concerns a new kind of 2nd Minkowski formula.
Lefschetz–Bott Fibrations on Line Bundles Over Symplectic Manifolds
Authors: Oba Takahiro
Published: May 2020

We describe Lefschetz–Bott fibrations on complex line bundles over symplectic manifolds explicitly. As an application, we show that the link of the $A_{k}$-type singularity has more than one strong symplectic filling up to homotopy and blow-up at points when the dimension of the link is greater than or equal to $5$. In the appendix, we show that the total space of a Lefschetz–Bott fibration over the unit disk serves as a strong symplectic filling of a contact manifold compatible with an open book induced by the fibration.
Pathways to Leadership: Reflections of Recent Infectious Diseases Society of America (IDSA) Leaders During Conception and Launch of the Inclusion, Diversity, Access, and Equity Movement Within the IDSA
Authors: Sears Cynthia L , Powderly William G , Auwaerter Paul G , Alexander Barbara D , File Thomas M
Published: May 2020

Opportunities for leadership in the specialty of infectious diseases (ID) have markedly increased over the last decade, including in newly recognized areas. Commensurate with the expansion of opportunities in ID, pathways to leadership positions within the Infectious Diseases Society of America (IDSA) are expanding as the Society seeks to advance the field for IDSA members. Acknowledging both the importance of diverse leaders to organizational success and shortfalls in diverse representation within IDSA leadership led to concentrated efforts to enhance transparency and opportunities for members to participate broadly in the work of IDSA. Herein, IDSA leaders reflect on their paths to IDSA leadership, hoping to help guide members seeking to partner with the Society. Features identified as important to individual success include mentorship, networking, participation in ID and IDSA volunteer experiences, passion for ID, and working with IDSA staff to advance the programs and initiatives of IDSA on behalf of members.
The Case for Why Africa Should Host COVID-19 Candidate Vaccine Trials
Authors: Singh Jerome Amir
Published: May 2020

In response to provocative comments by 2 European clinicians and scientists, the World Health Organization Director General has declared that Africa will not host COVID-19 vaccine trials. Such a stance risks stigmatizing COVID-19 vaccine trials in Africa and depriving Africa of critical research. To the contrary, there is a critical need for Africa to host COVID-19 vaccine trials on public health, scientific, and ethics grounds.
Implementation of an antimicrobial stewardship programme and reduction in carbapenemase-producing Enterobacterales in an Australian local health district
Authors: Cipko Kimberly , Cuenca Jose , Wales Erica , Harris Joanna , Bond Stuart , Newton Peter , Miyakis Spiros
Published: May 2020

Background

Carbapenemase-producing Enterobacterales (CPE) are increasingly seen in Australian hospitals. Antimicrobial stewardship (AMS) interventions have been shown to reduce rates of carbapenem-resistant organisms; data on their effect on CPE rates are limited.

Objectives

To explore the effect of a multi-site computer-supported AMS programme on the rates of CPE in an Australian local health district.

Methods

All laboratory CPE isolates between 2008 and 2018 were identified. Microbiological and demographic data, CPE risk factors and outcomes were collected. Monthly carbapenem use was expressed as DDD per 1000 occupied bed days (OBD). Hand hygiene compliance rates among healthcare workers were analysed. A computer-supported AMS programme was implemented district-wide in 2012. Bivariate relationships were examined using Pearson’s r and predictors of CPE isolates using time series linear regression.

Results

We identified 120 isolates from 110 patients. Numbers of CPE isolates and carbapenem use both showed a strong downward trend during the study period; the decreases were strongly correlated (r = 0.80, P = 0.006). The positive relationship between carbapenem use and CPE isolation was maintained while adjusting for time (b = 0.05, P < 0.001). Average yearly consumption of carbapenems fell by 20%, from 18.4 to 14.7 DDD/1000 OBD following implementation of the AMS programme. Hand hygiene compliance rates remained high throughout.

Conclusions

We demonstrated a reduction of CPE isolates in conjunction with reduced carbapenem use, longitudinally consolidated by a formal AMS programme. Prospective studies are needed to validate the effect of AMS on carbapenem resistance, especially in high-prevalence settings.
The Invention of a Chair Tradition in Ethiopia: A Case Study of Liminoid Design
Authors: Goss David
Published: May 2020

Both design and invention deal with future materializations, facilitating the environment and artefacts into different categories. These categories are conceptual constructs and any transgression of, combination of, or entering interstices between their imagined conceptual borders is Liminoid Design. Liminoid design is defined in this article as a momentary state of liminality: unstructuredness, transience, inter-categorical or uncategorizable. Though a very common phenomenon, it potentially creates new configurations of reality and new categories in design. This article describes manifestations of liminoid design, through the development of a contemporary Ethiopian chair with the merging of two categories: a side chair with imagery of the historic Aksum stelae. The Aksum stelae are monolithic stone monuments in northern Ethiopia erected during the ancient Kingdom of Aksum (in the early Christian period between the fourth and sixth centuries AD). This amalgamation emphasizes the contemporary connection to the past with a significant moment in Ethiopian history. Though seemingly traditional, this article identifies these chairs as a newly invented design type—the Aksum chair. During several visits to Ethiopia, I visited furniture workshops in Addis Ababa and Aksum and visited purchasers of the chairs as well. This helped the research to trace the proliferation and initiation of an invented traditional style.
Local labor markets and the persistence of population shocks: evidence from West Germany, 1939–1970
Authors: Braun Sebastian T , Kramer Anica , Kvasnicka Michael , Meier Philipp
Published: May 2020

This article studies the persistence of a large, unexpected and regionally very unevenly distributed population shock, the inflow of eight million ethnic Germans from Eastern Europe to West Germany after World War II. Using detailed census data from 1939 to 1970, we show that the shock proved persistent within local labor markets, but was largely reversed between labor markets. These results show that the choice of spatial units can significantly affect the estimated persistence of population shocks. They can thus help to explain why previous studies on the persistence of population shocks reached conflicting conclusions.
Association of Salivary Cholinesterase With Arthropod Vectors of Disease
Authors: Temeyer Kevin B , Schlechte Kristie G , Olafson Pia U , Drolet Barbara S , Tidwell Jason P , Osbrink Weste L A , Showler Allan T , Gross Aaron D , Pérez de León Adalberto A
Published: May 2020

Acetylcholinesterase (AChE) was previously reported to be present in saliva of the southern cattle tick, Rhipicephalus (Boophilus) microplus (Canestrini), with proposed potential functions to 1) reduce acetylcholine toxicity during rapid engorgement, 2) modulate host immune responses, and 3) to influence pathogen transmission and establishment in the host. Potential modulation of host immune responses might include participation in salivary-assisted transmission and establishment of pathogens in the host as has been reported for a number of arthropod vector-borne diseases. If the hypothesis that tick salivary AChE may alter host immune responses is correct, we reasoned that similar cholinesterase activities might be present in saliva of additional arthropod vectors. Here, we report the presence of AChE-like activity in the saliva of southern cattle ticks, Rhipicephalus (Boophilus) microplus; the lone star tick, Amblyomma americanum (Linnaeus); Asian tiger mosquitoes, Aedes albopictus (Skuse); sand flies, Phlebotomus papatasi (Scopoli); and biting midges, Culicoides sonorensis Wirth and Jones. Salivary AChE-like activity was not detected for horn flies Haematobia irritans (L.), stable flies Stomoxys calcitrans (L.), and house flies Musca domestica L. Salivary cholinesterase (ChE) activities of arthropod vectors of disease-causing agents exhibited various Michaelis–Menten KM values that were each lower than the KM value of bovine serum AChE. A lower KM value is indicative of higher affinity for substrate and is consistent with a hypothesized role in localized depletion of host tissue acetylcholine potentially modulating host immune responses at the arthropod bite site that may favor ectoparasite blood-feeding and alter host defensive responses against pathogen transmission and establishment.
The Challenges of Using Citizen Reporting to Improve Public Services: A Field Experiment on Solid Waste Services in Uganda
Authors: Buntaine Mark T , Hunnicutt Patrick , Komakech Polycarp
Published: May 2020

Governments around the world are investing in technologies that allow citizens to participate in the coproduction of public services by providing monitoring and feedback, but there is little evidence about how these initiatives affect the quality of public services. We implemented a large-scale field experiment that involved organizing 50 citizen reporters in each of 100 neighborhoods across Kampala, Uganda, to provide weekly reports to the municipal government about the delivery of solid waste services via an SMS-messaging platform, resulting in 23,856 reports during the 9-month study period. Citizen reporting did not reduce informal waste accumulation as targeted, which would indicate improvements to formal services. Using our observations as participants in the development and deployment of the reporting platform and interviews with staff at the government agency receiving the citizen reports, we show how the public generated inconsistent information that did not fit existing decision-making processes. We generalize lessons from this field experiment by explaining how coproduction involving information sharing through information and communication technologies is likely to affect public services based on the alignment of citizen-produced data with the information problems managers face; the search costs of detecting public services failures; the quality of citizen-produced data; and the operating costs of citizen-reporting platforms.
The chloroplast NADH dehydrogenase-like complex influences the photosynthetic activity of the moss Physcomitrella patens
Authors: Storti Mattia , Puggioni Maria Paola , Segalla Anna , Morosinotto Tomas , Alboresi Alessandro
Published: May 2020

Alternative electron pathways contribute to regulation of photosynthetic light reactions to adjust to metabolic demands in dynamic environments. The chloroplast NADH dehydrogenase-like (NDH) complex mediates the cyclic electron transport pathway around PSI in different cyanobacteria, algae, and plant species, but it is not fully conserved in all photosynthetic organisms. In order to assess how the physiological role of this complex changed during plant evolution, we isolated Physcomitrella patens lines knocked out for the NDHM gene that encodes a subunit fundamental for the activity of the complex. ndhm knockout mosses indicated high PSI acceptor side limitation upon abrupt changes in illumination. In P. patens, pseudo-cyclic electron transport mediated by flavodiiron proteins (FLVs) was also shown to prevent PSI over-reduction in plants exposed to light fluctuations. flva ndhm double knockout mosses had altered photosynthetic performance and growth defects under fluctuating light compared with the wild type and single knockout mutants. The results showed that while the contribution of NDH to electron transport is minor compared with FLV, NDH still participates in modulating photosynthetic activity, and it is critical to avoid PSI photoinhibition, especially when FLVs are inactive. The functional overlap between NDH- and FLV-dependent electron transport supports PSI activity and prevents its photoinhibition under light variations.
Role of spectral resolution for infrared asteroid compositional analysis using meteorite spectra
Authors: Skulteti A , Kereszturi A , Kereszty Zs , Pal B , Szabo M , Cipriani F
Published: May 2020

In this work the potential mineral identification of meteorites is analysed for the mid-infrared range, to evaluate observational possibilities for future missions targeting small body surfaces. Three carbonaceous and three ordinary chondrite meteorites are examined by a diffuse reflection (DRIFT) instrument, and the presence of principal minerals is confirmed by a powder diffraction method as well. The possibilities and constraints of mineral identifications in the mid-infrared are simulated by artificially degrading the spectral resolution. Our research shows that for the definite identification of principal mineral bands, a spectral resolution ≤10 cm−1 (≤0.15 μm) is needed. At 20–100 cm−1 (0.3–1.5 μm) resolution the identification of these minerals is uncertain, and with a resolution >100 cm−1, it is almost impossible.
A low-bias and sensitive small RNA library preparation method using randomized splint ligation
Authors: Maguire Sean , Lohman Gregory J S , Guan Shengxi
Published: May 2020

Small RNAs are important regulators of gene expression and are involved in human development and disease. Next generation sequencing (NGS) allows for scalable, genome-wide studies of small RNA; however, current methods are challenged by low sensitivity and high bias, limiting their ability to capture an accurate representation of the cellular small RNA population. Several studies have shown that this bias primarily arises during the ligation of single-strand adapters during library preparation, and that this ligation bias is magnified by 2′-O-methyl modifications (2′OMe) on the 3′ terminal nucleotide. In this study, we developed a novel library preparation process using randomized splint ligation with a cleavable adapter, a design which resolves previous challenges associated with this ligation strategy. We show that a randomized splint ligation based workflow can reduce bias and increase the sensitivity of small RNA sequencing for a wide variety of small RNAs, including microRNA (miRNA) and tRNA fragments as well as 2′OMe modified RNA, including Piwi-interacting RNA and plant miRNA. Finally, we demonstrate that this workflow detects more differentially expressed miRNA between tumorous and matched normal tissues. Overall, this library preparation process allows for highly accurate small RNA sequencing and will enable studies of 2′OMe modified RNA with new levels of detail.
Combining single-cell RNA-sequencing with a molecular atlas unveils new markers for Caenorhabditis elegans neuron classes
Authors: Lorenzo Ramiro , Onizuka Michiho , Defrance Matthieu , Laurent Patrick
Published: May 2020

Single-cell RNA-sequencing (scRNA-seq) of the Caenorhabditis elegans nervous system offers the unique opportunity to obtain a partial expression profile for each neuron within a known connectome. Building on recent scRNA-seq data and on a molecular atlas describing the expression pattern of ∼800 genes at the single cell resolution, we designed an iterative clustering analysis aiming to match each cell-cluster to the ∼100 anatomically defined neuron classes of C. elegans. This heuristic approach successfully assigned 97 of the 118 neuron classes to a cluster. Sixty two clusters were assigned to a single neuron class and 15 clusters grouped neuron classes sharing close molecular signatures. Pseudotime analysis revealed a maturation process occurring in some neurons (e.g. PDA) during the L2 stage. Based on the molecular profiles of all identified neurons, we predicted cell fate regulators and experimentally validated unc-86 for the normal differentiation of RMG neurons. Furthermore, we observed that different classes of genes functionally diversify sensory neurons, interneurons and motorneurons. Finally, we designed 15 new neuron class-specific promoters validated in vivo. Amongst them, 10 represent the only specific promoter reported to this day, expanding the list of neurons amenable to genetic manipulations.
Substrate specificities of Escherichia coli ItaT that acetylates aminoacyl-tRNAs
Authors: Zhang Chuqiao , Yashiro Yuka , Sakaguchi Yuriko , Suzuki Tsutomu , Tomita Kozo
Published: May 2020

Escherichia coli ItaT toxin reportedly acetylates the α-amino group of the aminoacyl-moiety of Ile-tRNAIle specifically, using acetyl-CoA as an acetyl donor, thereby inhibiting protein synthesis. The mechanism of the substrate specificity of ItaT had remained elusive. Here, we present functional and structural analyses of E. coli ItaT, which revealed the mechanism of ItaT recognition of specific aminoacyl-tRNAs for acetylation. In addition to Ile-tRNAIle, aminoacyl-tRNAs charged with hydrophobic residues, such as Val-tRNAVal and Met-tRNAMet, were acetylated by ItaT in vivo. Ile-tRNAIle, Val-tRNAVal and Met-tRNAMet were acetylated by ItaT in vitro, while aminoacyl-tRNAs charged with other hydrophobic residues, such as Ala-tRNAAla, Leu-tRNALeu and Phe-tRNAPhe, were less efficiently acetylated. A comparison of the structures of E. coli ItaT and the protein N-terminal acetyltransferase identified the hydrophobic residues in ItaT that possibly interact with the aminoacyl moiety of aminoacyl-tRNAs. Mutations of the hydrophobic residues of ItaT reduced the acetylation activity of ItaT toward Ile-tRNAIlein vitro, as well as the ItaT toxicity in vivo. Altogether, the size and shape of the hydrophobic pocket of ItaT are suitable for the accommodation of the specific aminoacyl-moieties of aminoacyl-tRNAs, and ItaT has broader specificity toward aminoacyl-tRNAs charged with certain hydrophobic amino acids.
Augsburg
Authors: Häberlein Mark
Published: May 2020

The imperial city of Augsburg figures prominently in the history and historiography of the Renaissance and the Protestant Reformation for several reasons. First, Augsburg was an eminent center of printing, artistic production, and humanist learning which also evolved into a major communication hub in the course of the sixteenth century. Second, the city’s name is associated with several crucial events of the period, such as Martin Luther’s interview with Cardinal Cajetan during the imperial diet of 1518; the Augsburg Confession, a Protestant statement of faith penned by Luther’s collaborator Philipp Melanchthon and presented to Emperor Charles V during the imperial diet of 1530; the Augsburg Interim, an essentially Catholic formulation of religious doctrine with some concessions to Protestants that the emperor imposed on the Holy Roman Empire in 1548; and the Religious Peace of Augsburg, a settlement between the emperor (represented by his brother, King Ferdinand) and the empire’s estates during the imperial diet of 1555. Third, Augsburg exemplifies the complexity of religious reform in some German communities. While cities such as Nuremberg or Zurich became associated with one particular strand of reform—Lutheranism or Zwinglianism—early on, various groups rivaled for ascendancy from the 1520s to the 1550s. Followers of Martin Luther were sidelined by adherents Ulrich Zwingli and the Strasbourg reformer Martin Bucer during the 1530s, and Anabaptists attracted a sizable following until the city government cracked down on them in the late 1520s. Meanwhile, the presence of prominent families such as the Fuggers and their close ties to the emperor ensured the survival of a Catholic minority. After years of hesitation and compromise, the city council adopted Protestantism officially in 1534–1537, prohibiting the Mass and dissolving the monasteries. Yet, after the defeat of the Schmalkaldic League in 1547, Emperor Charles V reintroduced Catholic worship in Augsburg and changed the city constitution, giving Catholic patricians (who were his strongest supporters) a disproportionate share of council seats and high administrative offices. The Religious Peace of Augsburg finally provided safeguards for Catholic minorities in imperial cities, thus paving the way for the institutionalized coexistence of the Lutheran and Catholic faiths in Augsburg. Fourth, historians of culture, gender, the urban poor, and marginal groups began to mine the extraordinarily rich holdings of Augsburg’s city archives in the final decades of the 20th century. They found that the city’s tax and court records contain a wealth of information on the common people, who left few records of their own. Augsburg has thus become the focus of a number of innovative studies that explore the social and cultural dimensions of the urban Reformation. It is due to these works that we know more about craftsmen, women, the poor, and the delinquent in Augsburg than in most other 16th-century German cities and towns.
Two children with extra-nodalMycobacterium aviumcomplex infection
Authors: Markland Ali , Tan Ben , Adamko Darryl , Diener Tania , Levett Paul N , Wiebe Sheldon , Wang Hui , Podberezin Mark , Saczek Krysztof , Milbrandt Kris , Essalah Abdulhafid , Quan William , Deneer Harry
Published: May 2020

Mycobacterium avium complex (MAC) is usually considered an opportunistic organism, which infects immunocompromised children or those with structural airway abnormalities. We present two cases of MAC infection affecting immune competent children, likely from hot tubs with primary involvement of pulmonary and urinary systems. These cases highlight the importance of asking about hot tub use in immune competent children with suspected or confirmed MAC infections.
Theory of generalized Josephson effects
Authors: Beekman Aron J
Published: May 2020

The DC Josephson effect is the flow of supercurrent across a weak link between two superconductors with different values of their order parameters, the phase. We formulate this notion for any kind of spontaneous continuous symmetry breaking. The quantity that flows between the two systems is the zero-wavenumber Noether current associated with the broken symmetry. The AC Josephson effect is the oscillation of current due to the energy difference between the two systems caused by an imposed asymmetric chemical potential of Noether charge. As an example of novel physics, a Josephson effect is predicted between two crystalline solids, potentially measurable as a force periodic in the separation distance.
ChurchInAction: the role of religious interventions in times of COVID-19
Authors: del Castillo Fides A , Biana Hazel T , Joaquin Jeremiah Joven B
Published: May 2020

In a recently published letter to the editor of this journal, the authors have called for the need to establish psychological support structures that cater to people’s mental health in this time of the coronavirus disease 2019 pandemic. To be more holistic, we extend this call to include people’s spiritual well-being as well. We highlight the initiatives of the Philippines’ religious sector. In particular, we report some of the interventions made by the Roman Catholic Church that have led to the social media hashtag, #ChurchInAction. These religious and spiritual interventions showcase the efforts of the Philippine Church and play an important role in providing assistance in time of public health crisis.
Promoter Activity-Based Case-Control Association Study onSLC6A4Highlighting Hypermethylation and Altered Amygdala Volume in Male Patients With Schizophrenia
Authors: Ikegame Tempei , Bundo Miki , Okada Naohiro , Murata Yui , Koike Shinsuke , Sugawara Hiroko , Saito Takeo , Ikeda Masashi , Owada Keiho , Fukunaga Masaki , Yamashita Fumio , Koshiyama Daisuke , Natsubori Tatsunobu , Iwashiro Norichika , Asai Tatsuro , Yoshikawa Akane , Nishimura Fumichika , Kawamura Yoshiya , Ishigooka Jun , Kakiuchi Chihiro , Sasaki Tsukasa , Abe Osamu , Hashimoto Ryota , Iwata Nakao , Yamasue Hidenori , Kato Tadafumi , Kasai Kiyoto , Iwamoto Kazuya
Published: May 2020

Associations between altered DNA methylation of the serotonin transporter (5-HTT)-encoding gene SLC6A4 and early life adversity, mood and anxiety disorders, and amygdala reactivity have been reported. However, few studies have examined epigenetic alterations of SLC6A4 in schizophrenia (SZ). We examined CpG sites of SLC6A4, whose DNA methylation levels have been reported to be altered in bipolar disorder, using 3 independent cohorts of patients with SZ and age-matched controls. We found significant hypermethylation of a CpG site in SLC6A4 in male patients with SZ in all 3 cohorts. We showed that chronic administration of risperidone did not affect the DNA methylation status at this CpG site using common marmosets, and that in vitro DNA methylation at this CpG site diminished the promoter activity of SLC6A4. We then genotyped the 5-HTT-linked polymorphic region (5-HTTLPR) and investigated the relationship among 5-HTTLPR, DNA methylation, and amygdala volume using brain imaging data. We found that patients harboring low-activity 5-HTTLPR alleles showed hypermethylation and they showed a negative correlation between DNA methylation levels and left amygdala volumes. These results suggest that hypermethylation of the CpG site in SLC6A4 is involved in the pathophysiology of SZ, especially in male patients harboring low-activity 5-HTTLPR alleles.
0020 Differentially Expressed Genes Using Saliva Samples from Nurses Rotating Shifts
Authors: Imes C C , Monica M A , Chasens E R , Conley Y P
Published: May 2020

Introduction

Globally, millions of people work night or rotating shifts (i.e., shift work), including nurses and other healthcare providers. Shift work can cause insufficient and mistimed sleep which disrupts the normal circadian rhythm. Shift work is associated with an increased risk for cardio-metabolic disorders and certain cancers. This descriptive, single group, within-subject, repeated-measures study explored the effect of shift work on gene expression levels in a sample of female nurses engaged in rotating shifts.

Methods

Saliva samples were collected from ten nurses without sleep or alertness medication use or a sleep disorder. The samples were collected using DNA Genotek RNA stabilizing saliva kits after participants worked at least 3 consecutive day shifts (~ 7:30 pm) and 3 consecutive night shifts (~7:30 am). Takara Smarter Stranded Total RNA Seq Kit was used following manufacturer’s instructions on an Illumina NextSeq500. CLC Genomic Workbench 12 (Qiagen) was used for quality control, aligning the sequence reads, normalization, and differential expression analyses. Genes with log2 fold changes of ± 2.0 were included in gene set enrichment and pathway analyses using Ingenuity Pathway Analysis (IPA; Qiagen).

Results

Participants were all female, white, and mostly healthy with a mean ± SD age of 27.2 ± 4.5 years. Compared to the post-day shift samples, a total of 287 genes were differentially expressed at a log2 fold change of ± 2.0 in the post-night shift samples. The genes with the greatest increase in expression levels were: PRDX5, SLC7A5, FCGR1A, DNAJC7, PSMD4, and PER1. The genes with the greatest decrease in expression levels were: PPIP5K2, SCART1, CASP10, SLC24A4, and OSBP. Based on the IPA analyses, the differentially expressed genes play a role in gene expression, cell signaling, cell death and survival, and RNA damage and repair.

Conclusion

Significant differential gene expression in pathways associated with poor health were observed among female nurses engaged in rotating shifts. Potential molecular and cellular functions were identified that may be the mechanisms resulting in the increased health risks associated with shift work.

Support

University of Pittsburgh School of Nursing Center for Research and Evaluation Pilot/Feasibility Study Program
0021 RNA Sequencing Reveals Transcriptomic Changes in Individuals with Insomnia
Authors: Mithani S , Yun S , Pattinson C , Kim H , Guedes V , Fink A , Weljie A , Gehrman P , Gill J
Published: May 2020

Introduction

Insomnia affects 10–20% of the US population and is associated with negative health and psychosocial sequelae. Despite the public health impact of insomnia little is known about its underlying molecular mechanisms. The purpose of this study is to examine differentially expressed genes in 15 patients with chronic insomnia and age- and sex-matched good sleepers (n=15).

Methods

We performed total RNA-seq on 30 whole blood samples collected at 09:00 at 150 bp paired-ends on the Illumina NovaSeq-6000 platform. Alignment was performed using the STAR version 2.7.2a software on the human reference genome (GRCh38). Differential gene expression analysis was performed using DESeq2 version 1.24.0. Pathway analysis was performed using IPA, release 2019-08-30.

Results

An average of 86.7 million paired end reads per sample were sequenced. We found that 289 genes were differentially expressed in insomnia patients with a log fold change (LFC) ±0.50 and had a FDR p-value < 0.05. Top dysregulated genes include CSMD1 (L2FC=-2.78; p=1.35E-06), DUX4L9 (L2FC=3.40; p=2.81E-06) and GRM4 (L2FC=2.45; p=4.50E-05). Among the functionally relevant genes, CSMD encodes a complement control protein that is known to participate in the complement activation and inflammation in the developing central nervous system. UTS2 (L2FC=1.778; p=8.94E-06) is involved in regulation of orexin A and B activity and rapid eye movement during sleep. Ingenuity Pathway Analysis revealed 3 associated networks: Hematological, Hereditary Disorder, Organismal Injury and Abnormalities (score: 46), Developmental, Hereditary Disorder, Metabolic Disease (score: 43), and Cell Cycle, Cell mediated Immune Response, Cellular Development (score: 43).

Conclusion

Overall, our study revealed dysregulated genes in individuals who suffer from insomnia. Notably, dysregulation of these functionally relevant genes could impair functional brain connectivity and synaptic function. Further investigation of these biological pathways will be useful to elucidate the pathogenesis of insomnia and identify novel biomarkers or drug targets for developing improved diagnostics and therapeutics.

Support

National Institutes of Nursing Research, Graduate Partnership Program
0034 When Should You Sleep to Maximize Alertness?
Authors: Vital-Lopez F , Doty T J , Balkin T J , Reifman J
Published: May 2020

Introduction

Working under sleep-restricted conditions may curtail safety and productivity. We could potentially minimize the negative effects of sleep restriction by optimizing the timing of sleep. However, to date, there are no algorithms that can determine the optimal sleep time to maximize alertness when most needed.

Methods

Our previously validated unified model of performance predicts the recuperative effects of sleep on alertness. Here, we extended this model to predict the likelihood of an individual falling and remaining asleep at any given moment, as a function of recent sleep history and time of day. Then, we combined the model with an optimization algorithm to provide optimal sleep recommendations for a given work/rest schedule. Specifically, using the model to predict the effectiveness of different sleep schedules, the algorithm determines when to sleep and for how long, so as to maximize alertness at desired times. The algorithm takes as inputs the 1) user-provided sleep history, 2) periods when the user has an opportunity to sleep, and 3) desired periods for maximum alertness, and provides as outputs sleep recommendations that are physiologically feasible and optimize alertness for the desired period. We assessed the algorithm by computing and comparing sleep recommendations for five previously published experimental studies of sleep restriction, including diurnal and nocturnal sleep.

Results

Compared to the original sleep schedules in the studies, our algorithm identified sleep recommendations that increased the predicted alertness by up to 33% and by 18% on average. These results suggest that the algorithm can tailor the timing of sleep to each specific sleep-restriction condition so as to maximize its benefits.

Conclusion

Our algorithm provides automated, customized guidance to enhance the recuperative benefits of limited sleep opportunities to maximize alertness at the most needed times. As such, it is the first quantitative sleep optimization tool for fatigue-management systems.

Support

This work was sponsored by the Military Operational Medicine Research Area Directorate of the U.S. Army Medical Research and Development Command, Ft. Detrick, MD.
0066 Glycinergic Postsynaptic Inhibition is Responsible for the Suppression of Hypoglossal Motoneuron Activity During Naturally-Occurring REM Sleep
Authors: Tobin C , Fung S J , Xi M , Chase M H
Published: May 2020

Introduction

The present study was undertaken to explore the role of glycinergic postsynaptic inhibition and monoaminergic disfacilitation (a withdrawal of excitatory noradrenergic and serotonergic inputs) in the control of hypoglossal motoneuron activity during REM sleep. Accordingly, glycinergic, noradrenergic and serotonergic antagonists were microinjected into the hypoglossal nucleus, and their effects on the hypoglossal nerve activity during REM sleep were examined in chronically-instrumented, unanesthetized cats.

Methods

Adults cats were prepared for monitoring behavioral states of sleep and wakefulness, and for extracellular recordings from hypoglossal nerve. Strychnine (a glycinergic antagonist) and a mixture of prazosin (a noradrenergic antagonist) and methysergide (a serotonergic antagonist) were microinjected, separately, into the hypoglossal nucleus during naturally-occurring states of sleep and wakefulness.

Results

During REM sleep, compared to non-REM sleep, the hypoglossal nerve activity decreased by 17.4±1.5% (n=17) in the control recordings (prior to the injection of strychnine). Following the microinjection of strychnine, there was only a mean decrease of 7.2±1.2% (n=12) in the nerve activity during REM sleep versus NREM sleep. The strychnine effect was statistically significant compared to control (p<0.001; unpaired t-test), which indicates that strychnine blocks REM sleep-related suppression of hypoglossal nerve activity. In contrast, the microinjection of prazosin and methysergide did not significantly reduce the hypoglossal nerve activity during REM sleep (control: 15.9±2.3, n=9 vs. prazosin+methysergide: 12.6±1.4%, n=10, p=0.229, unpaired t-test).

Conclusion

The present results demonstrate that the microapplication of strychnine, but not prazosin and methysergide, into the hypoglossal nucleus significantly reduces the suppression of the hypoglossal nerve activity during naturally-occurring REM sleep. We therefore suggest that glycinergic postsynaptic inhibition is primarily responsible for the suppression of hypoglossal motoneuron activity during REM sleep.

Support

5R01NS094062
0070 The Effects of Acute Blue Wavelength Light Exposure on Functional Brain Connectivity and Mood
Authors: Alkozei A , Dailey N S , Bajaj S , Vanuk J R , Raikes A C , Grandner M A , Killgore W D
Published: May 2020

Introduction

Blue wavelength light is an effective treatment for delayed sleep phase syndrome, seasonal affective disorder and bipolar depression. The role of blue light in regulating melatonin production has been extensively studied, but other potential neurophysiological effects remain poorly understood. Some studies have suggested that daily blue light exposure may modulate functional brain responses within the amygdala and prefrontal cortex (PFC), potentially explaining blue light’s antidepressant effect. In this study we investigated the effects of a single 30-minute session of blue light exposure on functional resting state connectivity between the amygdala and PFC.

Methods

Twenty-nine healthy 18–32 year olds were randomly assigned to either receive 30 minutes of blue (n=17) or non-blue (amber) light (n=12) exposure followed by a 7-minute resting state scan. Pre- and post light exposure, participants completed the Positive and Negative Affect Scale, as a measure of state affect.

Results

Individuals who received blue versus amber light showed greater positive connectivity between the right amygdala and the left dorsolateral prefrontal cortex (DLPFC) (x=-24, y=46, z=18, k=90, volume p-FDR corrected, p<0.001). Increased amygdala-DLFC connectivity correlated with greater decreases in negative mood for the blue (ρ=-.55, p=0.03), but not the amber group. Using Granger Causality, we found that the directionality of information flow between these two areas was bidirectional (p<0.0025).

Conclusion

Blue light exposure appears to facilitate greater information flow between the amygdala and the DLPFC at rest, potentially enhancing cognitive processes that regulate arousal and mood. As blue light exposure has been shown to enhance attention and learning, using blue light exposure during practice of emotional regulation strategies, such as reappraisal, may further increase the beneficial effects of blue light on mood. In order to use blue light exposure in a more targeted manner for sleep and mood disorders, further research into the underlying neurophysiological mechanisms is needed.

Support

This research was supported by a USAMRAA grant to WDSK (W81XWH-14-1-0571) as well as by an Arizona Health Education Centers (AHEC) Research Grant to AA.
0079 Blue Light Exposure Enhances Neural Efficiency of the Task Positive Network During a Cognitive Interference Task
Authors: Killgore W D , Dailey N S , Raikes A C , Vanuk J R , Taylor E , Grandner M A , Alkozei A
Published: May 2020

Introduction

Light exposure has powerful effects on the circadian timing of sleep and wake, primarily through the regulation of the secretion of melatonin. However, it is becoming clear that light has additional alerting effects beyond its primary effect on the circadian system. Exposure to light, particularly blue-wavelength light, has been shown to acutely increase brain activation, alertness, and some elementary aspects of cognitive performance such as working memory and emotional anticipation during the day. Whether blue light exposure can have longer-lasting effects on brain activation and performance during more complex cognitive control tasks up to 30-minutes after light cessation is unknown.

Methods

In a sample of 30 healthy adults, we examined the effects of a single 30-minute exposure to either blue (n=14) or amber placebo (n=16) light on subsequent brain activation and performance during the Multi-Source Interference Task (MSIT) measured a half-hour after light cessation using functional magnetic resonance imaging. Mean activation in all regions showing increased task-related activation (i.e., Task Positive Network; TPN) and regions showing decreased activation (i.e., Default Mode Network; DMN) at p<.001 (FWE corrected) was extracted separately for each network in SPM12 and compared between light conditions.

Results

Performance metrics for the MSIT, including accuracy, response time, and cognitive throughput, did not differ between the blue and amber conditions, suggesting that performance was sustained equally between light conditions. However, brain activation within the TPN to the interference condition of the MSIT was significantly lower (p=.024) in the blue relative to the amber condition, with no group differences observed for suppression of the DMN.

Conclusion

Compared to amber, a single exposure to blue light was associated with enhanced neural efficiency a half-hour later as demonstrated by reduced TPN activation to achieve the same level of cognitive performance. Blue light may be an effective method for optimizing neurocognitive performance under some conditions.

Support

US Army Medical Research and Materiel Command: W81XWH-14-1-0571
0083 Slow Wave Activity During Sleep is Associated with Longitudinal Change in Overnight Memory Recall
Authors: Buck C , Parker Fong K , Linkovski O , Kawai M , O’Hara R
Published: May 2020

Introduction

Duration of slow wave sleep (SWS) declines with age and may not be the most sensitive biomarker for memory in older adults. Analyzing the spectral power of slow wave activity (SWA) (0.5–4 Hz) may provide a more sensitive measure to capture the impact of sleep on memory. We investigated the association of SWA at baseline with the change of overnight memory recall over one year in older adults.

Methods

Participants were 42 community-dwelling healthy older adults (22 women and 20 men). We performed a polysomnography (PSG) and list-learning memory tests at baseline (T1) and after a one-year follow-up (T2). The procedure includes, 1) the participants memorized a 16 word list in the evening, 2) after a 5 minute delay, participants wrote down as many words as they could remember (evening recall), 3) overnight PSG was then performed, and 4) the following morning, participants wrote down as many words from the original list from the night before (overnight memory recall). This procedure was repeated at T2. Mixed modeling was utilized to analyze the association between baseline SWA and trajectory of overnight memory recall.

Results

For the SWA component, higher relative power of slow oscillation (0.5–1 Hz) during the first ultradian cycle at baseline was correlated with a greater decline in overnight memory recall after 1 year (t = -2.198, p = .034), which covaried for age and gender. There was no correlation with evening recall. Relative power of delta (1–4 Hz) range activity did not show an association with evening and overnight memory recall.

Conclusion

Higher relative power of slow oscillation at baseline predicts a greater decline of overnight memory recall. This may indicate a differential effect among the frequency ranges of SWA on longitudinal change in memory in older adults.

Support

This work was supported by National Institute of Health grants MH 070886, AG 18784 and AG17824 and the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs.