bluuebunny/crossref_metadata_2025 huggingface dataset:
Organization of Peptidoglycan Synthesis in Nodes and Separate Rings at Different Stages of Cell Division ofStreptococcus pneumoniae
Authors: Perez Amilcar J. , Boersma Michael J. , Bruce Kevin E. , Lamanna Melissa M. , Shaw Sidney L. , Tsui Ho-Ching T. , Taguchi Atsushi , Carlson Erin E. , VanNieuwenhze Michael S. , Winkler Malcolm E.
Published: September 2020

Bacterial peptidoglycan (PG) synthesis requires strict spatial and temporal organization to reproduce specific cell shapes. In the ovoid-shaped, pathogenic bacteriumStreptococcus pneumoniae(Spn), septal and peripheral (sidewall-like) PG synthesis occur simultaneously at midcell. To uncover the organization of proteins and activities that carry out these two modes of PG synthesis, we examinedSpncells vertically oriented onto their poles to image the division plane at the high lateral resolution of 3D-SIM (structured-illumination microscopy). Using fluorescent D-amino acid (FDAA) probes, we show that areas of new transpeptidase (TP) activity catalyzed by penicillin-binding proteins (PBPs) separate into a pair of concentric rings early in division, representing peripheral PG (pPG) synthesis (outer ring) and the leading-edge (inner ring) of septal PG (sPG) synthesis. Fluorescently tagged PBP2x or FtsZ locate primarily to the inner FDAA-marked ring, whereas PBP2b and FtsX remain in the outer ring, suggesting roles in sPG or pPG synthesis, respectively. Short pulses of FDAA labeling revealed an arrangement of separate regularly spaced “nodes” of TP activity around the division site of predivisional cells. Control experiments in wild-type and mutant strains support the interpretation of nodal spacing of TP activity, and statistical analysis confirmed that the number of nodes correlates with different ring diameters. This nodal pattern of FDAA labeling is conserved in other ovoid-shaped species. Tagged PBP2x, PBP2b, and FtsX proteins also exhibited nodal patterns with spacing comparable to that of FDAA labeling. Together, these results reveal a highly ordered PG synthesis apparatus in ovococcal bacteria at different stages of division.

SIGNIFICANCE

The spatial organization of PBPs and their TP activity at division septa is not well understood. In some bacteria, TP activity and PBP localization seem to be nodal (also called punctate), whereas in other bacteria, discrete foci of PBP activity are infrequently or not observed. Here we report two basic properties of the organization of PBPs and TP activity in the ovoid-shaped bacteriumSpn. First, there is distinct spatial separation of the sPG machine, including FtsZ, from the pPG synthesis machine at the midcell of dividingSpncells. Second, in predivisional cells, PBPs and TP activity are organized heterogeneously into regularly spaced nodes, whose number and dynamic distribution are likely driven by the PG synthesis of PBP:SEDS complexes.
An endoplasmic reticulum (ER) ATPase safeguards ER identity by removing ectopically localized mitochondrial proteins
Authors: Qin Qing , Zhao Ting , Zou Wei , Shen Kang , Wang Xiangming
Published: September 2020

Stringent targeting of membrane proteins to corresponding organelles is essential for organelle identity and functions. In addition to molecular pathways that target proteins to appropriate organelles, surveillance mechanisms clear mistargeted proteins from undesired destinations. While Msp1 functions on mitochondrial membrane to remove mistargeted proteins, the surveillance mechanism for the ER is not well understood. Here, we show that mitochondrial tail-anchored (TA) and signal-anchored (SA) proteins mislocalize to ER membrane in neurons and muscles inC. elegans catp-8mutants.catp-8encodes a conserved P5A type ATPase, which localizes to ER and removes ectopic mitochondrial TA/SA proteins from ER. Incatp-8mutant, mitochondria fission protein FIS-1 mislocalizes to ER membrane. Together with another mitochondria fission protein MFF-2, FIS-1 causes ER fragmentation in a Dynamin related protein (DRP-1) dependent manner. Additionally, CATP-8 is essential for dendrite development.catp-8mutant dramatically reduces the level of the dendrite guidance receptor DMA-1, leading to diminished dendritic arbors. Hence, P5A ATPase safeguards ER morphology and functions by preventing mitochondrial proteins mislocalization.

HIGHLIGHTS

CATP-8, a P5A type ATPase, localizes to ER and functions as a surveillance mechanism to remove mistargeted mitochondrial proteins.

Multiple mitochondria proteins are mistargeted to ER incatp-8mutants.

Ectopic recruitment of mitochondria fission mechinary to ER causes ER fragmentation incatp-8mutants.

CATP-8 is essential for PVD dendrite morphogenesis through modulating the level of transmembrane receptor DMA-1.
Encoding of environmental cues in central amygdala neurons during foraging
Authors: Ponserre Marion , Fermani Federica , Klein Rüdiger
Published: September 2020

In order to successfully forage in an environment filled with rewards and threats, animals need to rely on familiar structures of their environment that signal food availability. The central amygdala (CeA) is known to mediate a panoply of consummatory and defensive behaviors, yet how specific activity patterns within CeA subpopulations guide optimal choices is incompletely understood. In a paradigm of appetitive conditioning in which mice freely forage for food across a continuum of cues, we find that two major subpopulations of CeA neurons, Somatostatin-positive (CeASst) and protein kinase Cδ-positive (CeAPKCδ) neurons can assign motivational properties to environmental cues and encode memory of goal location. While the proportion of food responsive cells was higher within CeASstthan CeAPKCδneurons, only the activities of CeAPKCδ, but not CeASst, neurons were required for learning of contextual food cues. Since CeAPKCδneurons are known to promote a range of defensive behaviors, our findings point to a model in which CeA circuit components are not organized in specialized functional units but can process both aversive and rewarding information in a context and experience dependent manner.

HIGHLIGHTS

Two populations of central amygdala (CeA) neurons, CeAPKCδand CeASstneurons can assign motivational properties to environmental cues and encode memory of goal location.

The proportion of food responsive cells was higher among CeASst, than CeAPKCδneurons.

The activities of CeAPKCδ, but not CeASst, neurons are required for learning of contextual food cues. CeAPKCδneurons represent a “general encoding” population selecting defensive and appetitive responses depending on context.
Lyl-1 regulates primitive macrophages and microglia development
Authors: Wang Shoutang , Ren Deshan , Kaushik Anna-Lila , Matherat Gabriel , Lécluse Yann , Filipp Dominik , Vainchenker William , Raslova Hana , Plo Isabelle , Godin Isabelle
Published: September 2020

During ontogeny, macrophages (MΦ) populations emerge in the Yolk Sac (YS) via two distinct progenitor waves, prior to hematopoietic stem cell development. MΦ-progenitors from the primitive/”early EMP” and transient-definitive/”late EMP” waves both contribute to various resident-MΦ populations in the developing embryonic organs. Identifying factors that modulates early stages of MΦ-progenitor development may lead to a better understanding of defective function of specific resident-MΦ subsets.

Here we show that primitive macrophage (MΦPrim) progenitors in the YS express Lyl-1, a bHLH transcription factor related to SCL/Tal-1. Transcriptomic analysis of YS MΦ-progenitors indicated that MΦPrimprogenitors present at embryonic day (E) 9 are clearly distinct from those present at later stages. Disruption of Lyl-1 basic helix-loop-helix domain led initially to an early increased emergence of MΦPrimprogenitors, and later to their defective differentiation. These defects were associated with a disrupted expression of gene sets related to embryonic patterning and neurodevelopment. Lyl-1-deficiency also induced a reduced production of mature MΦ/microglia in the early brain, as well as a transient reduction of the microglia pool at midgestation and in the newborn.

We thus identify Lyl-1 as a critical regulator of MΦPrimand microglia development, which disruption may impair resident-MΦ function during organogenesis.

Key points

1- Yolk sac primitive macrophage progenitors and microglia/Border Associated macrophages express Lyl-1.

2- Lyl-1-deficiency impairs primitive macrophage and microglia development and leads to the up-regulation of gene sets related to embryo patterning and neuro-development.
The structure of kaliophilite KAlSiO4, a long-lasting crystallographic problem
Authors: Mugnaioli Enrico , Bonaccorsi Elena , Lanza Arianna E. , Elkaim Erik , Diez-Gómez Virginia , Sobrados Isabel , Gemmi Mauro , Gregorkiewitz Miguel
Published: September 2020

Kaliophilite is a feldspathoid mineral found in two Italian magmatic provinces and represents one of the 12 known phases with composition close to KAlSiO4. Despite its apparently simple formula, the structure of this mineral revealed extremely complex and resisted structure solution for more than a century. Samples from the Vesuvius–Monte Somma and Alban Hills volcanic areas were analyzed through a multi-technique approach, and finally the crystal structure of kaliophilite was solved using 3D electron diffraction and refined against X-ray diffraction data of a twinned crystal. Results were also ascertained by the Rietveld method using synchrotron powder intensities. It was found that kaliophilite crystallizes in space groupP3 with unit-cell parametersa= 27.0597 (16),c= 8.5587 (6) Å,V= 5427.3 (7) Å3andZ= 54. The kaliophilite framework is a variant of the tridymite topology, with alternating SiO4and AlO4tetrahedra forming sheets of six-membered rings (63nets), which are connected along [001] by sharing the apical oxygen atoms. Considering the up (U) and down (D) orientations of the linking vertex, kaliophilite is the first framework that contains three different ring topologies: nine (1-3-5) (UDUDUD) rings, six (1-2-3) (UUUDDD) rings and twelve (1-2-4) (UUDUDD) rings. This results in a relatively open (19.9 tetrahedra nm−3) channel system with multiple connections between the double six-ring cavities. Such a framework requires a surprisingly large unit cell, 27 times larger than the cell of kalsilite, the simplest phase with the same composition. The occurrence of some Na for K substitution (3–10%) may be related to the characteristic structural features of kaliophilite. Micro-twinning, pseudo-symmetries and anisotropichkl-dependent peak broadening were also detected, and they may account for the elusive character of the kaliophilite crystal structure.
A methodology for classification and validation of customer datasets
Authors: Nie Dongyun , Cappellari Paolo , Roantree Mark
Published: September 2020

Purpose

The purpose of this paper is to develop a method to classify customers according to their value to an organization. This process is complicated by the disconnected nature of a customer record in an industry such as insurance. With large numbers of customers, it is of significant benefit to managers and company analysts to create a broad classification for all customers.

Design/methodology/approach

The initial step is to construct a full customer history and extract a feature set suited to customer lifetime value calculations. This feature set must then be validated to determine its ability to classify customers in broad terms.

Findings

The method successfully classifies customer data sets with an accuracy of 90%. This study also discovered that by examining the average value for key variables in each customer segment, an algorithm can label the group of clusters with an accuracy of 99.3%.

Research limitations/implications

Working with a real-world data set, it is always the case that some features are unavailable as they were never recorded. This can impair the algorithm’s ability to make good classifications in all cases.

Originality/value

This study believes that this research makes a novel contribution as it automates the classification of customers but in addition, the approach provides a high-level classification result (recall and precision identify the best cluster configuration) and detailed insights into how each customer is classified by two validation metrics. This supports managers in terms of market spend on new and existing customers.
Stay at (which) home: second homes during and after the COVID-19 pandemic
Authors: Zoğal Volkan , Domènech Antoni , Emekli Gözde
Published: September 2020

Purpose

This viewpoint paper aims to provide reflections on the role of second homes in the tourism and housing markets together with future lines of research during and after the first outbreak of the COVID-19 (coronavirus disease 2019) pandemic. The authors aim to review the epistemological evolution of the term “second homes” because of the pandemic, as well as to unfold possible short-, medium- and long-term effects that could place second homes at the center of tourist activity and of the tourist rental market profitability.

Design/methodology/approach

This paper is based on published research studies about the definition of the term “second homes”, as well as media sources related to their role during the current situation of the first outbreak of the COVID-19 pandemic.

Findings

In the early stages of the pandemic, second-home owners migrated from crowded cities to low-density areas, being vectors of transmission of the virus. Now, a potential shift in tourist preferences could position second homes at the center of tourist activity as soon as travel restrictions are reduced. This could intensify existing processes of commodification of housing, empowering accommodation platforms and situating the potential for profiteering around the tourist rental market. Parallely, international interests in migrating from crowded cities to low-density areas could also be triggered.

Originality/value

This viewpoint is presented as the confinement measures associated with the new pandemic are being de-escalated in most of the western countries. It is expected that sharing it will provide insights to researchers and practitioners to better plan their research around secondary housing. Its role should be analysed from different perspectives: in the spread of the virus to low-density areas to anticipate mitigation actions in future outbreaks; in the recovery process of (domestic) tourism; in the processes of commodification and financialization of housing in tourist areas; and their impacts on local residents.
Leadership competencies of first-level military leaders
Authors: Meerits Artur , Kivipõld Kurmet
Published: September 2020

Purpose

The purpose of this paper is to determine the quality of the leadership competencies of first-level military leaders according to three behavioural dimensions: task, change and relational competencies.

Design/methodology/approach

The study was conducted in the Estonian Defence Forces (EDF) among first-level commanders (N = 89), whose leadership competencies were assessed by their subordinates (N = 1,655). The Leader Reward and Punishment Questionnaire was used to assess task competencies, the Transformational Leadership Behaviour Inventory was used to assess change competencies and the Extended Authentic Leadership Measure was used to assess relational competencies. Cluster analyses were conducted to identify the level of leadership competencies in the sample and to determine the commanders' leadership profile.

Findings

The study reveals that in terms of leadership competencies, only two competencies from task, two from change and none from the relational dimension are sufficient. In addition, the results highlight that the relational competencies of leadership are connected to each other, while task and change leadership competencies are not.

Practical implications

The study results make it possible to work out the main principles for a leadership development programme for first-level commanders. In addition, the developed methodology makes it possible to assess the leadership competencies of individual commanders using the three-dimensional framework.

Originality/value

This paper demonstrates how quality of the leadership competencies and profiles of first-level EDF commanders are determined within three behavioural dimensions: task, change and relational competencies.
Herbivory improves the fitness of predatory beetles
Authors: Ugine Todd A. , Nagra Avneet , Grebenok Robert J. , Behmer Spencer T. , Losey John E.
Published: September 2020

While many predatory arthropods consume non‐prey foods from lower trophic levels, little is known about what drives the shift from predator to omnivore. Predatory lady beetles often consume non‐prey foods like plant foliage and pollen. One species, Coccinella septempunctata, eats foliage to redress sterol deficits caused by eating sterol‐deficient prey. Here we explore how omnivory benefits lady beetle fitness.

We reared seven species of lady beetles—from five genera distributed across the tribe Coccinellini—on pea aphids in the presence or absence of fava bean foliage; pea aphids have very low sterol content. Foliage supplements lengthened the development times of four species and decreased survival to adulthood of two species; it had no effect on adult mass. We mated beetles in a 2 × 2 factorial design (males with or without foliage paired with females with or without foliage). For each species, we observed a profound paternal effect of foliage supplements on fitness. Females mated to foliage‐supplemented males laid more eggs and more viable eggs compared to females mated to non‐supplemented males. Foliage‐supplemented males produced 2.9–4.6 times more sperm compared to non‐supplemented males for the three species we examined.

We analysed the sterol profile of four beetle species reared on pea aphids—with or without foliage—and compared their sterol profile to field‐collected adults. For two laboratory‐reared species, sterols were not detected in adult male beetles, and overall levels were generally low (total ng of sterol/beetle range: 3–33 ng); the exception being Propylea quatuordecimpunctata females (total ng of sterol/beetle range: 50–157 ng). Laboratory‐reared lady beetle sterol content was not significantly affected by the presence of foliage. Field‐collected beetles had higher levels of sterols compared to laboratory‐reared beetles (2,452–145,348 ng per beetle); cholesterol and sitosterol were the dominant sterols in both field‐collected and laboratory‐reared beetles.

Our findings indicate that herbivory benefits lady beetle fitness across the Coccinellini, and that this was entirely a paternal effect. Our data provide a rare example of a nutritional constraint impacting fitness in a sex‐specific manner. It also shows, more broadly, how a nutritional constraint can drive predators towards omnivory.
‘A holistic approach’: incorporating sustainability into biopedagogies of healthy eating in Sweden’s dietary guidelines
Authors: Bergman Karolin , Lövestam Elin , Nowicka Paulina , Eli Karin
Published: September 2020

Dietary guidelines can be considered a pedagogical tool, designed to promote healthy eating at the population level. In this study, we critically examine the biopedagogies implicated in Sweden’s official dietary guidelines. Published in 2015, these guidelines take a potentially innovative ‘holistic approach’ to food and eating, addressing the challenge of formulating dietary advice that considers both human health and environmental concerns. Applying Bacchi´s ‘What’s the problem represented to be?’ approach, we interrogate how the guidelines frame the interplay of public health concerns and environmental concerns in making food choices. We find that the biopedagogies of sustainable eating, as presented in these guidelines, implicate the subject position of theideal eater. The ideal eater values sustainability, has high cultural capital, and draws on both taste and nutritional knowledge to make good food choices. However, while the ideal eater is expected to be aware of environmental issues, these are incorporated into the ideal eater’s choices only in addition to the primary concern of health. Thus, although the guidelines frame a ‘holistic approach’ as the solution to both health and environmental concerns, in cases where health and environmental priorities conflict, the guidelines’ biopedagogies of sustainable eating align with earlier biopedagogies of healthy eating.
Threat, emboldenment, or both? The effects of political power on violent hate crimes*
Authors: Dugan Laura , Chenoweth Erica
Published: September 2020

How do expressions of support or opposition by the U.S. federal government, influence violent hate crimes against specific racial and ethnic minorities? In this article, we test two hypotheses derived from Blalock's (1967) conceptualization of intergroup power contests. The political threat hypothesis predicts that positive government attention toward specific groups would lead to more hateful violence directed against them. The emboldenment hypothesis predicts that negative government attention toward specific groups would also lead to more hateful violence directed against them. Using combined data on U.S. government actions and federal hate crime statistics from 1992 through 2012, vector autoregression models provide support for both hypotheses, depending on the protected group involved. We conclude that during this period, African Americans were more vulnerable to hate crimes motivated by political threat, and Latinx persons were more vulnerable to hate crimes motivated by emboldenment.
Thinking about gun violence
Authors: Cook Philip J.
Published: September 2020

The Stockholm Prize for 2020 was awarded for research on gun violence and its prevention, and recognizes the growing depth and scope of this field. I am honored to be a co‐recipient, together with Franklin E. Zimring. This essay focuses on three of the topics that have been on my agenda over the course of the last 45 years: how best to conceptualize and measure the problem of gun violence; the availability of guns to violent offenders; and how and why to improve police investigations of criminal shooting incidents, including assaults and homicides.
Prevalence of malnutrition risk and poor food intake in older adults in Indian hospitals: A prospective observational nutritionDay study with novel mapping of malnutrition risk to the Malnutrition Screening Tool
Authors: Wright Charlene , Shankar Bhuvaneshwari , Marshall Skye , Pearcy Joshua , Somani Ananya , Agarwal Ekta
Published: September 2020

Aim

Current literature regarding the prevalence and consequences of poor dietary intake and risk of malnutrition in older adults is limited to wealthier regions including the United States, Europe and Australasia. With a rapidly ageing population in India, this prospective observational study aimed to evaluate hospital food intake and malnutrition risk and their impact on hospital length of stay, readmission rates and in‐hospital mortality of older adults in Indian hospitals.

Methods

Data collected during nutritionDay worldwide audits (2014‐2016), in five urban, private hospitals in India included baseline demographic and clinical data on patients aged ≥60 years. Proportion of food consumed at one main meal was recorded and data on length of stay, readmissions and in‐hospital mortality were collected 30 days post‐baseline.

Results

A total of 262 participants (mean age: 69 ± 8 years; 65% males) were recruited. Mapped malnutrition risk (mapped Malnutrition Screening Tool [mMST] score ≥ 2) on admission was 31% and increased to 44% during the course of hospitalisation. Over one quarter of participants consumed ≤50% of their meal (28%). Over half the participants were found to be eating poorly (59%) and those identified as at risk of malnutrition were not offered additional nutrition support. The median LOS was 8 days (range: 1‐92), 30‐day readmission rates were 7% and in‐hospital mortality was 0.4%. Malnutrition risk and poor food intake were not associated with health‐related outcomes.

Conclusion

Older adults in Indian acute care hospitals have a noticeable prevalence of malnutrition risk and poor food intake. There is an opportunity for future research to focus on identifying and managing nutritional issues.
Forging Indian Religion: East India Company Servants and the Construction of ‘Gentoo’/‘Hindoo’ Scripture in the 1760s
Authors: Patterson Jessica
Published: September 2020

This article demonstrates how, in the 1760s, two British East India Company servants, John Zephaniah Holwell and Alexander Dow, constructed a particular interpretation of India's ancient religious past through creative misrepresentations of mysteriously sourced texts. This had broad ramifications for contemporary understandings of Indian religion, and has important implications for the historiography of Orientalism in this period. Just as forgeries in the literary sphere challenged notions of history, introducing scepticism, alternative narratives and national mythologies, so in the field of Orientalist letters they shaped an idea of Indian religion that could both challenge European assumptions and facilitate imperial ideologies.
Rare cystic lymphangioma in the chest wall of an adult patient: A case report and comprehensive review of the literature
Authors: Song Shuai , Chang Dong , Li Hao , Li Bowen , Xu Kaikai , Liu Chunquan , Cui Yong
Published: September 2020

Lymphangiomatosis is a rare, benign, hyperproliferative hamartoma composed of dilated lymphatic vessels. Cystic lymphangioma (CL) in the chest wall in an adult patient is rare, but we focus on this type of patient in our present case study. A 54‐year‐old female patient with a painless mass in her chest wall went without treatment for two years following diagnosis. After consenting to treatment, Doppler color flow imaging (DCFI), chest CT, and MRI revealed a cystic lesion with multiple thin septula in the left chest. Surgical resection was performed, and histopathological examination identified a cystic lymphangioma. The patient did not experience recurrence during the follow‐up period.
Sex differences in the acute effects of oral and vaporized cannabis among healthy adults
Authors: Sholler Dennis J. , Strickland Justin C. , Spindle Tory R. , Weerts Elise M. , Vandrey Ryan
Published: September 2020

Policy changes have increased access to cannabis for individuals with little or no prior exposure. Few studies have examined sex differences in cannabis effects among individuals with sporadic cannabis use or for nonsmoked routes of cannabis administration. Data from four double‐blind, placebo‐controlled studies were pooled to compare the acute pharmacodynamic effects of vaporized and oral cannabis in male (n = 27) and female (n = 23) participants who used cannabis infrequently (no use ≥30 days prior to randomization). Analyses compared peak change‐from‐baseline scores between male and female participants for subjective drug effects, cognitive/psychomotor performance, cardiovascular effects, and blood concentrations of Δ9‐tetrahydrocannabinol (THC) and its primary metabolites (11‐OH‐THC, THC‐COOH) after exposure to placebo cannabis or cannabis containing low‐dose (5 or 10 mg) or high‐dose THC (20 or 25 mg). Overall, cannabis elicited dose‐orderly increases in subjective effects, impairment of cognitive/psychomotor performance, heart rate, and blood cannabinoid concentrations. Females exhibited greater peak blood 11‐OH‐THC concentrations and reported greater peak subjective ratings of “drug effect” that remained when controlling for body weight. When controlling for both body weight and peak blood cannabinoid concentrations, ratings of “anxious/nervous,” “heart racing,” and “restless” were significantly higher for females than males. Although additional research is needed to elucidate sex differences in responses to cannabis at a wider range of THC doses, other routes of administration, and products with diverse chemical composition, the current data indicate that public health messaging and clinical decision making around the use of cannabinoids should recommend lower starting doses for females and warnings about acute anxiogenic reactions.
The impact of introducing Palliative Care Needs Rounds into rural residential aged care: A quasi‐experimental study
Authors: Rainsford Suzanne , Liu Wai‐Man , Johnston Nikki , Glasgow Nicholas
Published: September 2020

Objective

This study examined the impact of introducing Palliative Care Needs Rounds (hereafter Needs Rounds) into residential aged care on hospitalisations (emergency department presentations, admissions and length of stay) and documentation of advance care plans.

Design

A quasi‐experimental study.

Setting

Two residential aged care facilities in one rural town in the Snowy Monaro region of New South Wales, Australia.

Participants

The intervention group consisted of all residents who died during the study period (April 2018‐March 2019), and included a subgroup of decedents who were discussed in a Needs Round. The control cohort included all residents who died in the three‐year period prior to introducing Needs Rounds (2015‐2017).

Intervention

Needs Rounds are monthly onsite triage/risk stratification meetings where case‐based education and staff support help to identify residents most at risk of dying without an adequate plan in place. Needs Rounds were attended by residential aged care staff and led by a palliative medicine physician.

Main outcome measures

Decedents’ hospitalisations (emergency department presentations, admissions and length of stay) in the last three months of life, place of death and documentation of advance care plans.

Results

Eleven Needs Rounds were conducted between April and September 2018. The number of documented advance care plans increased (P < .01). There were no statistically significant changes in hospitalisations or in‐hospital deaths.

Conclusion

Needs Rounds are an effective approach to increase the documentation of advance care plans within rural residential aged care. Further studies are required to explore the rural influence on outcomes including hospital transfers and preferred place of death.
Veiled apologetics and insurgent nostalgia: Sociogenesis of contested memories of the Marcos dictatorship
Authors: Uyheng Joshua , Roxas Gilana Kim T. , Herras Martina Magpusao
Published: September 2020

Across many nascent democracies, living historical memories of past conflicts are vulnerable to contestation. Past scholarship explains such mnemonic dissonances as the outcome of either broad cultural scripts or top‐down political maneuvering. Building on these insights, we utilize the concept of sociogenesis to show how contested memories are semiotically mediated within institutional and informal spaces. Across two studies, we employ mixed methods designs to examine social representations of the Marcos dictatorship in the Philippines, using (a) nationally endorsed history textbooks (N = 86 pages), and (b) online comments (N = 9605) on public YouTube videos (N = 978). We find that textbooks construct the dictatorship in terms of veiled apologetics, leveraging representational strategies of balanced reportage to commensurate the dictatorship’s legacies of abuse against contributions to economic and infrastructure programs. Meanwhile, social media messages represent the regime in terms of insurgent nostalgia, which yearns for a mythologized past under the strongman Marcos in rejection of an elite‐coded democratic present. We discuss implications of our findings for broader social psychological discussions of living historical memories in the context of structural fragility, linking to related debates on critical history education, digital democracy, and the resurgence of authoritarianism locally and worldwide.
Biopolitical Violence and Waiting: Hotspot as a Biopolitical Borderzone
Authors: Topak Özgün E.
Published: September 2020

This paper conceptualises Lesvos hotspot as a biopolitical borderzone where migrants experience concentrated violent practices of borders, including legal exclusion, presence of exclusionary surveillance and absence of surveillance for safety, degrading living conditions, and waiting. The paper also discusses the biopolitical consequences of these practices for migrants such as physical illnesses and injuries, and psychological disorders. The paper contributes to the scholarship on biopolitical borders in two main ways. First, through conceptualising hotspot as a form of biopolitical borderzone and demonstrating the specific biopolitical practices in the Lesvos hotspot and their effects on migrants. Second, through highlighting the key role of waiting in the operations of the biopolitical border. The paper demonstrates how waiting is entangled in a complex way with other biopolitical practices and how it both creates and amplifies biopolitical effects for migrants.
If we don’t change direction soon, we’ll end up where we’re going: a description of the SSY Engine
Authors: Heijl Anders , Brandel Magnus
Published: September 2020

Data presented during the first two decades of this millennium has shed valuable light on how the intraocular pressure (IOP) is linked to glaucomatous progression. Large prospective controlled trials have confirmed that there is a correlation between the change in intraocular pressure (IOP) and the risk for visual field progression. The magnitude of the effect, as indicated by these studies, is a 10–15% decrease in risk for a 1 mmHg drop in IOP. The risk is correlated with the rate at which patients develops field loss, that is the Rate of Progression or RoP, which in turn makes future projections of a patient’s progression over time at a given IOP level a reasonable possibility. This led to the creation of the SSY (Save Sight Years) concept and later the SSY engine, which is a practical application of this model in the form of a web application. This article describes the thinking behind this system, how it works, the caveats and where we think it can benefit clinical practice.
Clinical significance of personalized tacrolimus dosing by adjusting to donor CYP3A‐status in liver transplant recipients
Authors: Csikány Nóra , Kiss Ádám , Déri Máté , Fekete Ferenc , Minus Annamária , Tóth Katalin , Temesvári Manna , Sárváry Enikő , Bihari László , Gerlei Zsuzsa , Kóbori László , Monostory Katalin
Published: September 2020

Aims

Donor's CYP3A‐status (CYP3A5 genotype and CYP3A4 expression) can provide prognostic information regarding tacrolimus‐metabolizing capacity of the liver graft and initial tacrolimus dosing for therapeutic blood concentrations in liver transplants. The present work prospectively investigated whether CYP3A‐status guided tacrolimus therapy has any potential clinical benefit for recipients in the early postoperative period.

Methods

The contribution of preliminary assaying of donor CYP3A‐status to the optimization of initial tacrolimus therapy and to the reduction of adverse events (acute rejection, infection, nephrotoxicity) was investigated in 112 liver transplant recipients (CYPtest group) comparing to 101 control patients on tacrolimus concentration guided therapy.

Results

The time for achieving therapeutic tacrolimus concentration was significantly reduced, confirming potential benefit of initial tacrolimus therapy adjusted to donor's CYP3A‐status over classical clinical practice of tacrolimus concentration guided treatment (4 vs 8 days, P < 0.0001). Acute rejection episodes (3.6 vs 23.8%, P < 0.0001) and tacrolimus induced nephrotoxicity (8 vs 27%, P = 0.0004) were less frequent in CYPtest group than in control patients, whereas occurrence of infectious disease was not influenced by tacrolimus dosing strategy (3.6 vs 5.9% in CYPtest and control groups, P > 0.05). Acute rejection was often accompanied with tacrolimus blood concentrations lower than 10 ng mL−1 (20/24 of control and 2/4 of CYPtest patients), while nephrotoxicity was associated with high tacrolimus concentrations (>20 ng mL−1) in the first week after transplantation (13/27 of control and 2/9 of CYPtest patients).

Conclusion

CYP3A‐status guided therapy significantly improved the risk of misdosing induced early adverse effects (acute rejection, nephrotoxicity).
Metabolic effects of carvedilol through β‐arrestin proteins: investigations in a streptozotocin‐induced diabetes rat model and in C2C12 myoblasts
Authors: Güven Berna , Kara Zümra , Onay‐Beşikci Arzu
Published: September 2020

Background and Purpose

Carvedilol is a third‐generation β‐adrenoceptor antagonist, which also stimulates β‐arrestins. β‐arrestins initiate intracellular signalling and are involved in insulin release and sensitivity. Carvedilol is superior in effectiveness to other drugs that are used for similar indications and does not cause insulin resistance or diabetes, which can occur with other β‐antagonists. We have shown that carvedilol increased glucose usage in C2C12 cells. We investigate the biased agonist efficacy of carvedilol on β‐arrestins.

Experimental Approach

Streptozotocin (STZ)‐induced diabetes rat model was used to induce metabolic and cardiac disorders. After 8 weeks of diabetes, animals were treated with carvedilol or vehicle for another 4 weeks. In vitro heart function was evaluated at baseline as well as with increasing concentrations of isoprenaline. Effects of diabetes and carvedilol treatment on β‐arrestins, ERK, PPARα, CD36 proteins and pyruvate kinase activity were evaluated. β‐arrestins were silenced in C2C12 cells by using siRNA. Acute effects of carvedilol on ERK, CD36, mitochondrial transcription factor A, cardiolipin proteins and citrate synthase activity were investigated.

Key Results

Carvedilol reversed the deterioration of cardiac function in diabetes and diabetes‐induced decrease in β‐arrestins in rats. Carvedilol decreased the expression of CD36 in diabetes and increased mitochondrial transcription factor A and cardiolipin proteins. Silencing of β‐arrestins in cells prevented the effects of carvedilol on these proteins.

Conclusion and Implications

The metabolic effects of carvedilol seem to be related to biased activation of β‐arrestins. Patients with cardiovascular and metabolic disorders may benefit from new compounds that selectively act on β‐arrestins.
Oxysterols in cancer management: From therapy to biomarkers
Authors: Kloudova‐Spalenkova Alzbeta , Holy Petr , Soucek Pavel
Published: September 2020

Oxysterols are oxidized derivatives of cholesterol, both endogenous and exogenous. They have been implicated in numerous pathologies, including cancer. In addition to their roles in carcinogenesis, proliferation, migration, apoptosis, and multiple signalling pathways, they have been shown to modulate cancer therapy. They are known to affect therapy of hormonally positive breast cancer through modulating oestrogen receptor activity. Oxysterols have also been shown in various in vitro models to influence efficacy of chemotherapeutics, such as doxorubicin, vincristine, cisplatin, 5‐fluorouracil, and others. Their effects on the immune system should also be considered in immunotherapy. Selective anti‐cancer cytotoxic properties of some oxysterols make them candidates for new therapeutic molecules. Finally, differences in oxysterol levels in blood of cancer patients in different stages or versus healthy controls, and in tumour versus non‐tumour tissues, show potential of oxysterols as biomarkers for cancer management and patient stratification for optimization of therapy.

LINKED ARTICLES

This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc
Adipose tissue is a key organ for the beneficial effects of GLP‐2 metabolic function
Authors: Ejarque Miriam , Sabadell‐Basallote Joan , Beiroa Daniel , Calvo Enrique , Keiran Noelia , Nuñez‐Roa Catalina , Rodríguez Maria del Mar , Sabench Fatima , del Castillo Daniel , Jimenez Veronica , Bosch Fatima , Nogueiras Ruben , Vendrell Joan , Fernández‐Veledo Sonia
Published: September 2020

Background and Purpose

Glucagon‐like peptide‐2 (GLP‐2) is a gastrointestinal hormone released in response to nutritional intake that exerts a wide range of effects by activating GLP‐2 receptors. In addition to its intestinotrophic effects, GLP‐2 also positively influences glucose metabolism under conditions of obesity, but the mechanisms behind this remain unclear. Here, we have investigated the molecular role of the GLP‐2/GLP‐2 receptor axis in energetic metabolism, focusing on its potential modulatory effects on adipose tissue.

Experimental Approach

Physiological measurements (body weight, food intake, locomotor activity, and energy expenditure) and metabolic studies (glucose and insulin tolerance tests) were performed on lean and obese mice treated with the protease‐resistant GLP‐2 analogue teduglutide.

Key Results

Acute but not chronic centrally administered teduglutide decreased food intake and weight‐gain. By contrast, chronic activation of peripheral GLP‐2 receptors increased body weight‐independent glucose tolerance and had anti‐inflammatory effects on visceral adipose tissue. Using a gene silencing approach, we found that adipose tissue is necessary for these beneficial effects of teduglutide. Finally, teduglutide regulates the inflammatory state and acts as an anabolic signal in human adipocytes.

Conclusion and Implications

Overall, our data identify adipose tissue as a new, clinically relevant, site of action for GLP‐2 activity in obesity.

LINKED ARTICLES

This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc
Associations and risk factors for dental trauma: A systematic review of systematic reviews
Authors: Magno Marcela Baraúna , Nadelman Patricia , Leite Karla Lorene de França , Ferreira Daniele Masterson , Pithon Matheus Melo , Maia Lucianne Cople
Published: September 2020

Objective

We sought to revise, qualify and summarize the body of evidence based on current information on the known associations and risk factors for traumatic dental injury (TDI) occurrence with an overview of systematic reviews.

Methods

Electronic searches were performed with no language nor date restrictions.According to the PECO strategy, systematic reviews that investigated participants (P) with (E) and without (O) the presentation of factors relating to TDI and these factors’ association with TDI episodes (O) as primary or secondary outcomes were included. Quality assessment and bias control were carried out according to the AMSTAR 2 checklist. In cases of systematic review results of discordance, the Jadad decision algorithm was applied.

Results

After titles, abstracts and full texts were read, 19 systematic reviews were included in this overview. Four were classified with critically low, eleven with low and four with moderate methodological quality, respectively. In all studies, 249 cross‐sectional, 34 epidemiological surveys, 22 cohort, 9 case‐control, 4 longitudinal, 3 ecological and 30 unspecified studies were included. Male gender, child age, greater overjet, inadequate lip coverage, anterior open bite, caries in the permanent dentition, overweight, a previous history of TDI, tongue piercing, the use of alcoholic beverages and participation in sports were all associated with a greater chance of suffering TDI.

Conclusions

Sociodemographic, clinical and environmental factors are associated with a greater chance of TDI occurrence. However, most of the systematic reviews included were of a low quality and may not provide an accurate and comprehensive summary of the available research that addresses the question of interest. Well‐designed primary studies on different aspects of TDI are encouraged to provide higher quality scientific evidence.
Impaired small airway function in non‐asthmatic chronic rhinosinusitis with nasal polyps
Authors: Du Kun , Zheng Ming , Zhao Yan , Xu Wenbin , Hao Yun , Wang Yue , Zhao Jinming , Zhang Nan , Wang Xiangdong , Zhang Luo , Bachert Claus
Published: September 2020

Background

There is clinical evidence for impaired lung function in chronic rhinosinusitis with nasal polyps (CRSwNP) patients, which may be due to a high incidence of asthma comorbidity. The lung function characteristics of non‐asthmatic CRSwNP patients are not known. Small airway dysfunction (SAD) is involved in the pathogenesis of asthma. However, whether SAD is detected in non‐asthmatic patients with CRSwNPs remains unclear.

Objective

This study analysed the lung function of non‐asthmatic patients with CRSwNPs and evaluated its clinical relevance in CRSwNPs.

Methods

The clinical data for 191 consecutive CRSwNP patients (73 asthmatic and 118 non‐asthmatic) and 30 control subjects were prospectively collected. The patients were followed up for at least 3 years (mean [standard deviation], 42.47 ± 8.38 months). Serum and tissue total IgE levels were measured in 95 and 93 patients, respectively. Tissue eosinophil counts were documented in 63 patients.

Results

Non‐asthmatic CRSwNP patients had decreased forced expiratory flow at 75% of the FVC (FEF75) and FEF50 compared to the control subjects, and this difference was related to the severity of CRSwNP. The risk factors for impaired lung function in asthmatic and non‐asthmatic patients were duration of asthma and smoking. A multivariate logistic analysis showed that decreased FEF50 was associated with the recurrence of non‐asthmatic CRSwNPs. The lung function of CRSwNP patients negatively correlated with the degree of type‐2 inflammation, which was defined by the levels of Eos and IgE in polyp tissues and blood. The SAD of non‐asthmatic CRSwNP patients was related to serum IgE levels.

Conclusions and clinical relevance

This study provides evidence that non‐asthmatic CRSwNP patients may have SAD, which correlated with the severity and recurrence of CRSwNP. The decreased lung function of patients with CRSwNP was related to the degree of type‐2 inflammation.
Antithymocyte induction dosing and incidence of opportunistic viral infections using steroid‐free maintenance immunosuppression
Authors: Von Stein Lauren , Leino Abbie D. , Pesavento Todd , Rajab Amer , Winters Holli
Published: September 2020

Background

Currently, there is limited literature evaluating rATG induction dosing and incidence of opportunistic viral infections when using steroid‐free maintenance immunosuppression.

Methods

This single‐center, retrospective, study compared high rATG (>4.5 mg/kg) versus low (<4.5 mg/kg) induction dosing and the overall incidence of early opportunistic viral infection at 180 days in the setting of maintenance immunosuppression consisting of tacrolimus, mycophenolate, rapid steroid withdrawal, and a tiered antiviral prevention strategy based on donor‐recipient Cytomegalovirus (CMV) serostatus.

Results

A total of 209 patients were included; 76 patients received low‐dose and 133 patients received high‐dose rATG. Incidence of overall opportunistic viral infection occurred more frequently in patients who received high compared to low dose (29.8% vs 25% p = .030). Incidence of CMV infection was also significantly increased in the high‐dose group (31.6% vs 18.4% p = .039). In a multivariable model, rATG dose, as a continuous variable, remained a significant independent predictor of infection along with CMV risk (OR 1.46, 95% CI 1.02‐2.09) controlling for age and CMV risk. There were no differences in graft‐related outcomes at 180 days.

Conclusion

Higher cumulative rATG induction dose was associated with increased incidence of opportunistic viral infections, in the setting of a steroid‐free maintenance immunosuppression in the early post‐transplant period.