bluuebunny/crossref_metadata_2025 huggingface dataset:
Postgraduate ethics training programs: a systematic scoping review
Authors: Hong Daniel Zhihao , Goh Jia Ling , Ong Zhi Yang , Ting Jacquelin Jia Qi , Wong Mun Kit , Wu Jiaxuan , Tan Xiu Hui , Toh Rachelle Qi En , Chiang Christine Li Ling , Ng Caleb Wei Hao , Ng Jared Chuan Kai , Ong Yun Ting , Cheong Clarissa Wei Shuen , Tay Kuang Teck , Tan Laura Hui Shuen , Phua Gillian Li Gek , Fong Warren , Wijaya Limin , Neo Shirlyn Hui Shan , Lee Alexia Sze Inn , Chiam Min , Chin Annelissa Mien Chew , Krishna Lalit Kumar Radha
Published: June 2021

Background

Molding competent clinicians capable of applying ethics principles in their practice is a challenging task, compounded by wide variations in the teaching and assessment of ethics in the postgraduate setting. Despite these differences, ethics training programs should recognise that the transition from medical students to healthcare professionals entails a longitudinal process where ethics knowledge, skills and identity continue to build and deepen over time with clinical exposure.

A systematic scoping review is proposed to analyse current postgraduate medical ethics training and assessment programs in peer-reviewed literature to guide the development of a local physician training curriculum.

Methods

With a constructivist perspective and relativist lens, this systematic scoping review on postgraduate medical ethics training and assessment will adopt the Systematic Evidence Based Approach (SEBA) to create a transparent and reproducible review.

Results

The first search involving the teaching of ethics yielded 7669 abstracts with 573 full text articles evaluated and 66 articles included. The second search involving the assessment of ethics identified 9919 abstracts with 333 full text articles reviewed and 29 articles included. The themes identified from the two searches were the goals and objectives, content, pedagogy, enabling and limiting factors of teaching ethics and assessment modalities used. Despite inherent disparities in ethics training programs, they provide a platform for learners to apply knowledge, translating it to skill and eventually becoming part of the identity of the learner. Illustrating the longitudinal nature of ethics training, the spiral curriculum seamlessly integrates and fortifies prevailing ethical knowledge acquired in medical school with the layering of new specialty, clinical and research specific content in professional practice. Various assessment methods are employed with special mention of portfolios as a longitudinal assessment modality that showcase the impact of ethics training on the development of professional identity formation (PIF).

Conclusions

Our systematic scoping review has elicited key learning points in the teaching and assessment of ethics in the postgraduate setting. However, more research needs to be done on establishing Entrustable Professional Activities (EPA)s in ethics, with further exploration of the use of portfolios and key factors influencing its design, implementation and assessment of PIF and micro-credentialling in ethics practice.
Correction to: The role of JMJD6/U2AF65/AR-V7 axis in castration-resistant prostate cancer progression
Authors: Tong Dali
Published: June 2021

An amendment to this paper has been published and can be accessed via the original article.
Insecticide resistance exerts significant fitness costs in immature stages of Anopheles gambiae in western Kenya
Authors: Osoro Joyce K. , Machani Maxwell G. , Ochomo Eric , Wanjala Christine , Omukunda Elizabeth , Munga Stephen , Githeko Andrew K. , Yan Guiyun , Afrane Yaw A.
Published: June 2021

Background

Despite increasing documentation of insecticide resistance in malaria vectors against public health insecticides in sub-Saharan Africa, there is a paucity of information on the potential fitness costs of pyrethroid resistance in malaria vectors, which is important in improving the current resistant management strategies. This study aimed to assess the fitness cost effects of insecticide resistance on the development and survival of immature Anopheles gambiae from western Kenya.

Methods

Two-hour old, first instar larvae (L1) were introduced and raised in basins containing soil and rainwater in a semi-field set-up. Each day the number of surviving individuals per larval stage was counted and their stage of development were recorded until they emerged as adults. The larval life-history trait parameters measured include mean larval development time, daily survival and pupal emergence. Pyrethroid-resistant colony of An. gambiae sensu stricto and susceptible colony originating from the same site and with the same genetic background were used. Kisumu laboratory susceptible colony was used as a reference.

Results

The resistant colony had a significantly longer larval development time through the developmental stages than the susceptible colony. The resistant colony took an average of 2 days longer to develop from first instar (L1) to fourth instar (L4) (8.8 ± 0.2 days) compared to the susceptible colony (6.6 ± 0.2 days). The development time from first instar to pupa formation was significantly longer by 3 days in the resistant colony (10.28 ± 0.3 days) than in susceptible colony (7.5 ± 0.2 days). The time from egg hatching to adult emergence was significantly longer for the resistant colony (12.1 ± 0.3 days) than the susceptible colony (9.6 ± 0.2 days). The pupation rate (80%; 95% (CI: 77.5–83.6) vs 83.5%; 95% (CI: 80.6–86.3)) and adult emergence rate (86.3% vs 92.8%) did not differ between the resistant and susceptible colonies, respectively. The sex ratio of the females to males for the resistant (1:1.2) and susceptible colonies (1:1.07) was significantly different.

Conclusion

The study showed that pyrethroid resistance in An. gambiae had a fitness cost on their pre-imaginal development time and survival. Insecticide resistance delayed the development and reduced the survivorship of An. gambiae larvae. The study findings are important in understanding the fitness cost of insecticide resistance vectors that could contribute to shaping resistant management strategies.
An update on the distribution, bionomics, and insecticide susceptibility of Anopheles stephensi in Ethiopia, 2018–2020
Authors: Balkew Meshesha , Mumba Peter , Yohannes Gedeon , Abiy Ephrem , Getachew Dejene , Yared Solomon , Worku Amha , Gebresilassie Araya , Tadesse Fitsum G. , Gadisa Endalamaw , Esayas Endashaw , Ashine Temesgen , Ejeta Desta , Dugassa Sisay , Yohannes Mekonnen , Lemma Wossenseged , Yewhalaw Delenasaw , Chibsa Sheleme , Teka Hiwot , Murphy Matt , Yoshimizu Melissa , Dengela Dereje , Zohdy Sarah , Irish Seth
Published: June 2021

Background

Anopheles stephensi, an invasive malaria vector, was first detected in Africa nearly 10 years ago. After the initial finding in Djibouti, it has subsequently been found in Ethiopia, Sudan and Somalia. To better inform policies and vector control decisions, it is important to understand the distribution, bionomics, insecticide susceptibility, and transmission potential of An. stephensi. These aspects were studied as part of routine entomological monitoring in Ethiopia between 2018 and 2020.

Methods

Adult mosquitoes were collected using human landing collections, pyrethrum spray catches, CDC light traps, animal-baited tent traps, resting boxes, and manual aspiration from animal shelters. Larvae were collected using hand-held dippers. The source of blood in blood-fed mosquitoes and the presence of sporozoites was assessed through enzyme-linked immunosorbent assays (ELISA). Insecticide susceptibility was assessed for pyrethroids, organophosphates and carbamates.

Results

Adult An. stephensi were collected with aspiration, black resting boxes, and animal-baited traps collecting the highest numbers of mosquitoes. Although sampling efforts were geographically widespread, An. stephensi larvae were collected in urban and rural sites in eastern Ethiopia, but An. stephensi larvae were not found in western Ethiopian sites. Blood-meal analysis revealed a high proportion of blood meals that were taken from goats, and only a small proportion from humans. Plasmodium vivax was detected in wild-collected An. stephensi. High levels of insecticide resistance were detected to pyrethroids, carbamates and organophosphates. Pre-exposure to piperonyl butoxide increased susceptibility to pyrethroids. Larvae were found to be susceptible to temephos.

Conclusions

Understanding the bionomics, insecticide susceptibility and distribution of An. stephensi will improve the quality of a national response in Ethiopia and provide additional information on populations of this invasive species in Africa. Further work is needed to understand the role that An. stephensi will have in Plasmodium transmission and malaria case incidence. While additional data are being collected, national programmes can use the available data to formulate and operationalize national strategies against the threat of An. stephensi.
Early glycolytic reprogramming controls microglial inflammatory activation
Authors: Cheng Junjie , Zhang Rong , Xu Zhirou , Ke Youliang , Sun Renjuan , Yang Huicui , Zhang Xiaohu , Zhen Xuechu , Zheng Long-Tai
Published: June 2021

Background

Microglial activation-mediated neuroinflammation plays an important role in the progression of neurodegenerative diseases. Inflammatory activation of microglial cells is often accompanied by a metabolic switch from oxidative phosphorylation to aerobic glycolysis. However, the roles and molecular mechanisms of glycolysis in microglial activation and neuroinflammation are not yet fully understood.

Methods

The anti-inflammatory effects and its underlying mechanisms of glycolytic inhibition in vitro were examined in lipopolysaccharide (LPS) activated BV-2 microglial cells or primary microglial cells by enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, immunoprecipitation, flow cytometry, and nuclear factor kappa B (NF-κB) luciferase reporter assays. The anti-inflammatory and neuroprotective effects of glycolytic inhibitor, 2-deoxoy-d-glucose (2-DG) in vivo were measured in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-or LPS-induced Parkinson’s disease (PD) models by immunofluorescence staining, behavior tests, and Western blot analysis.

Results

We found that LPS rapidly increased glycolysis in microglial cells, and glycolysis inhibitors (2-DG and 3-bromopyruvic acid (3-BPA)), siRNA glucose transporter type 1 (Glut-1), and siRNA hexokinase (HK) 2 abolished LPS-induced microglial cell activation. Mechanistic studies demonstrated that glycolysis inhibitors significantly inhibited LPS-induced phosphorylation of mechanistic target of rapamycin (mTOR), an inhibitor of nuclear factor-kappa B kinase subunit beta (IKKβ), and NF-kappa-B inhibitor alpha (IκB-α), degradation of IκBα, nuclear translocation of p65 subunit of NF-κB, and NF-κB transcriptional activity. In addition, 2-DG significantly inhibited LPS-induced acetylation of p65/RelA on lysine 310, which is mediated by NAD-dependent protein deacetylase sirtuin-1 (SIRT1) and is critical for NF-κB activation. A coculture study revealed that 2-DG reduced the cytotoxicity of activated microglia toward MES23.5 dopaminergic neuron cells with no direct protective effect. In an LPS-induced PD model, 2-DG significantly ameliorated neuroinflammation and subsequent tyrosine hydroxylase (TH)-positive cell loss. Furthermore, 2-DG also reduced dopaminergic cell death and microglial activation in the MPTP-induced PD model.

Conclusions

Collectively, our results suggest that glycolysis is actively involved in microglial activation. Inhibition of glycolysis can ameliorate microglial activation-related neuroinflammatory diseases.
Zoonotic vaccinia virus strains belonging to different genetic clades exhibit immunomodulation abilities that are proportional to their virulence
Authors: Lourenço Karine Lima , Chinália Leandro Andrade , Henriques Lethícia Ribeiro , Rodrigues Rodrigo Araújo Lima , da Fonseca Flávio Guimarães
Published: June 2021

Background

The vaccinia virus (VACV) isolates,Guarani P1 virus (GP1V) and Passatempo virus (PSTV), were isolated during zoonotic outbreaks in Brazil. Each one of them belongs to two different VACV clades, defined by biological aspects that include virulence in mice and phylogenetic analysis. Considering that information about how vaccinia viruses from different groups elicit immune responses in animals is scarce, we investigated such responses in mice infected either by GP1V (group 2) or PSTV (group 1), using VACV Western Reserve strain (VACV-WR) as control.

Methods

The severity of the infections was evaluated in BALB/c mice considering diverse clinical signs and defined scores, and the immune responses triggered by GP1V and PSTV infections were analysed by immune cell phenotyping and intra-cytoplasmic cytokines detection.

Results

We detected a reduction in total lymphocytes (CD3 +), macrophages (CD14 +), and NK cells (CD3-CD49 +) in animals infected with VACV-WR or GP1V. The VACV-WR and GP1V viruses, belonging to the most virulent group in a murine model, were able to down-modulate the cell immune responses upon mice infection. In contrast, PSTV, a virus considered less virulent in a murine model, showed little ability to down-modulate the mice immune responses. Mice infected with VACV-WR and GP1V viruses presented significant weight loss and developed lesions in their spleens, as well as damage to liver and lungs whereas mice infected with PSTV developed only moderate clinical signs.

Conclusions

Our results suggest that VACV immunomodulation in vivo is clade-related and is proportional to the strain’s virulence upon infection. Our data corroborate the classification of the different Brazilian VACV isolates into clades 1 and 2, taking into account not only phylogenetic criteria, but also clinical and immunological data.
Brexit and trade policy: an analysis of the governance of UK trade policy and what it means for health and social justice
Authors: van Schalkwyk May C. I. , Barlow Pepita , Siles-Brügge Gabriel , Jarman Holly , Hervey Tamara , McKee Martin
Published: June 2021

Background

There is an extensive body of research demonstrating that trade and globalisation can have wide-ranging implications for health. Robust governance is key to ensuring that health, social justice and sustainability are key considerations within trade policy, and that health risks from trade are effectively mitigated and benefits are maximised. The UK’s departure from the EU provides a rare opportunity to examine a context where trade governance arrangements are being created anew, and to explore the consequences of governance choices and structures for health and social justice. Despite its importance to public health, there has been no systematic analysis of the implications of UK trade policy governance. We therefore conducted an analysis of the governance of the UK’s trade policy from a public health and social justice perspective.

Results

Several arrangements required for good governance appear to have been implemented – information provision, public consultation, accountability to Parliament, and strengthening of civil service capacity. However, our detailed analyses of these pillars of governance identified significant weaknesses in each of these areas.

Conclusion

The establishment of a new trade policy agenda calls for robust systems of governance. However, our analysis demonstrates that, despite decades of mounting evidence on the health and equity impacts of trade and the importance of strong systems of governance, the UK government has largely ignored this evidence and failed to galvanise the opportunity to include public health and equity considerations and strengthen democratic involvement in trade policy. This underscores the point that the evidence alone will not guarantee that health and justice are prioritised. Rather, we need strong systems of governance everywhere that can help seize the health benefits of international trade and minimise its detrimental impacts. A failure to strengthen governance risks poor policy design and implementation, with unintended and inequitable distribution of harms, and ‘on-paper’ commitments to health, social justice, and democracy unfulfilled in practice. Although the detailed findings relate to the situation in the UK, the issues raised are, we believe, of wider relevance for those with an interest of governing for health in the area of international trade.
RETRACTED ARTICLE: H3K27ac-induced lncRNA PAXIP1-AS1 promotes cell proliferation, migration, EMT and apoptosis in ovarian cancer by targeting miR-6744-5p/PCBP2 axis
Authors: Ma Yimin , Zheng Wei
Published: June 2021

We aimed to explore role of lncRNA PAX-interacting protein 1-antisense RNA1 (PAXIP1-AS1) in ovarian cancer (OC). RT-qPCR analysis identified upregulation of PAXIP1-AS1 in OC cell lines. Functionally, PAXIP1-AS1 knockdown inhibited cell proliferation, accelerated cell apoptosis, and suppressed cell migration and epithelial-mesenchymal transition (EMT) process. Upregulation of PAXIP1-AS1 was induced by CBP-mediated H3K27 acetylation (H3K27ac) via bioinformatic analysis and ChIP assay. Furthermore, PAXIP1-AS1 served as a competing endogenous RNA (ceRNA) to regulate PCBP2 expression by sponging microRNA-6744-5p (miR-6744-5p). Restoration experiments showed that overexpressed PCBP2 rescued effects of silenced PAXIP1-AS1 on cell proliferation, apoptosis, migration and EMT. Overall, lncRNA PAXIP1-AS1 activated by H3K27ac functioned as a tumor promoter in OC via mediating miR-6744-5p/PCBP2 axis, which provided promising insight into exploration on OC therapy.
Evaluation of adherence monitoring system using evriMED with a differentiated response compared to standard of care among drug-sensitive TB patients in three provinces in South Africa: a protocol for a cluster randomised control trial
Authors: Maraba Noriah , Orrell Catherine , Chetty-Makkan Candice M. , Velen Kavindhran , Mukora Rachel , Page-Shipp Liesl , Naidoo Pren , Mbatha M. Thulani , Fielding Katherine L. , Charalambous Salome
Published: June 2021

Background

South Africa has achieved drug-susceptible TB (DS-TB) treatment success of only 77% among people with new and previously treated TB. Alternative approaches are required to improve medication adherence and treatment completion to limit transmission, TB relapse and the development of resistance. This study aims to implement and evaluate the use of adherence medication monitors (Wisepill evriMED 1000) with a differentiated response to patient care, among DS-TB patients in three provinces of South Africa.

Methods

In total, 18 public health clinics across three provinces were selected. Clinics were randomised to intervention or standard of care clinics. In each clinic, approximately 145 DS-TB patients are being enrolled to reach a total of 2610. All patients have their daily adherence monitored using medication monitors. In the intervention arm, patients are receiving medication monitor reminders and differentiated care in response to adherence data. This weekly review of daily real-time monitoring will be undertaken from a central database. The differentiated care model includes automated SMS reminders with a missed dose, research staff-initiated phone call to the patient with a second or third missed dose, a home visit if four or more doses are missed, and motivational counselling if four or more doses are missed repeatedly. Fidelity of the intervention will be measured through process evaluation. Patients in control clinics will receive medication monitors for adherence tracking, standard of care TB education, and normal clinic follow-up procedures. The primary outcome is the proportion of patients by arm with >80% adherence, as measured by the medication monitor. The feasibility and acceptability of the intervention will be assessed by in-depth interviews with patients, stakeholders, and study staff. A cost effectiveness analysis of the intervention and standard of care clinics will be conducted.

Significance

This trial will provide evidence for the use of an intervention, including medication monitors and differentiated care package, to improve adherence to TB treatment. Improved adherence should also improve TB treatment completion rates, thus reducing loss to follow-up rates, and TB relapse among people with TB. The intervention is intended to ultimately improve overall TB control and reduce TB transmission in South Africa.

Trial registration

Pan African Trial Registry PACTR201902681157721. Registered on 11 February 2019.
Allisartan ameliorates vascular remodeling through regulation of voltage-gated potassium channels in hypertensive rats
Authors: Zhang Xiaoqin , Zhao Ziying , Xu Chunfang , Zhao Fengping , Yan Zhiqiang
Published: June 2021

Background

The objective of the present study was to determine the effect of allisartan, a new angiotensin II type 1 receptor antagonist on vascular remodeling through voltage gated potassium channels (Kv7) in hypertensive rats.

Methods

The study included a total of 47 Sprague Dawley (SD) rats. The animals were randomized to sham operation (n = 14), untreated hypertensive control group (n = 18) and allisartan treatment group (n = 15). Using renal artery stenosis, hypertension was induced in animals. Single dose of allisartan was administered intra-gastrically to animals in the allisartan treatment group and match placebo in the other 2 groups. Wire myography was used to measure the muscle tension in isolated mesenteric arteries from the animals. Real-time polymerase chain reaction was used to quantify the expression of Kv7 channel mRNA subunits.

Results

After 4 weeks of treatment, a significant decrease in mean arterial, systolic and diastolic blood pressure (SBP and DBP) was observed in allisartan treatment group compared to hypertension control group. The median arterial wall thickness and area/diameter ratio reduced significantly in treatment group compared to untreated hypertension group (P < 0.05). Wire myography demonstrated increased relaxation of mesenteric artery with increase in concentration of ML213. A significant up-regulation in the expression of all Kv7 mRNA subunits was observed in allisartan group compared to untreated hypertension group.

Conclusions

From the results, allisartan was found to lower BP and preserve vascular remodeling through Kv7 channels.
Growth Hormone Treatment for Adults With Prader-Willi Syndrome: A Meta-Analysis
Authors: Rosenberg Anna G W , Passone Caroline G B , Pellikaan Karlijn , Damiani Durval , van der Lely Aart J , Polak Michel , Bernardo Wanderley M , de Graaff Laura C G
Published: June 2021

Context

Features of Prader-Willi syndrome (PWS) overlap with features of growth hormone (GH) deficiency, like small hands and feet, short stature, increased body fat, and low muscle mass and strength. In children with PWS, GH treatment (GHt) improves physical health and cognition. GHt has become the standard of care in PWS children, but in adults this is not yet the case.

Objective

This work aims to provide an overview of the current knowledge on GHt in PWS adults.

Methods

Medline, Embase, and the Cochrane Central Register of Controlled Trials databases were searched. Study selection included randomized clinical trials (RCTs) and nonrandomized (un)controlled trials (NRCTs) that reported data for adults with PWS, who received GHt for at least 6 months. Data on body composition, body mass index (BMI), cardiovascular end points, bone, cognitive function, quality of life, and safety were extracted.

Results

Nine RCTs and 20 NRCTs were included. Body composition improved during 12 months of GHt with an increase in mean (95% CI) lean body mass of 1.95 kg (0.04 to 3.87 kg) and a reduction of mean (95% CI) fat mass of –2.23% (–4.10% to –0.36%). BMI, low-density lipoprotein cholesterol levels, fasting glucose levels, and bone mineral density did not change during GHt. There were no major safety issues.

Conclusion

GHt appears to be safe and improves body composition in adults with PWS. Because poor body composition is closely linked to the observed high incidence of cardiovascular morbidity in adults with PWS, improving body composition might reduce cardiovascular complications in this vulnerable patient group.
Flat Stevie Smith
Authors: Masud Noreen
Published: June 2021

Critics of Stevie Smith’s work often lean on the word “flat.” Usually, the term is meant to evoke Smith’s “simplicity” and lack of ornamentation, her refusal to lift into “poetic resonance,” or her unreadable tone. This essay attends more closely to flatness in Smith’s work, exploring the ways Smith finds flatness fascinating and proposing that the language of the “flat,” in all its senses, offers an illuminating way of grappling with the difficulty of her puzzling and unsettling prose and poetry. It unpacks the idea of the “flat”—a word that claims implicitly that no unpacking remains to be done—foregrounding the diversity of flatness’s associated emotions, as well as the ways it remains compelling. Drawing out the breadth of aesthetic and interpretative connotations that flatness holds for her, the essay argues, provides a coherent way of reading her work. Beginning with an examination of how “feeling flat” involves, for Smith, a diverse and complex set of emotions, the essay moves into outlining how flat landscapes offer Smith a mode of lingering habitation that derives its interest precisely from the absence of anything evidently interesting. In the process, it offers a critical language with which to approach other twentieth-century writers, such as D. H. Lawrence, whose work has remained elusive precisely because of its insistence that it has made its meaning abundantly available—that it has nothing to hide.
Meritorious Heroes
Authors: Kho Youenhee
Published: June 2021

This study explores the allegorical usage of hawk painting to praise a hero with meritorious deeds in Yuan China (1271–1368) and early Chosŏn Korea (1392–1910). Through an analysis of Yuan-dynasty poems inscribed on hawk paintings, this article demonstrates that paintings of a hawk sitting still on a tree in the woods conveyed the allegory of a hero subduing wily beings, such as rabbits and foxes. Moreover, Yuan paintings of a hawk and a bear (yingxiong 鷹熊) employed a Chinese rebus and represented the animals as heroes, comparing them to historical heroic and loyal figures. This article then turns to Chosŏn Korea, where two types of hawk paintings reflected the Korean reception of Yuan counterparts. One was the painting of a hawk sitting still, which indicated the hero's readiness for future achievements. Another, with the motif of a rabbit caught in the hawk's talons, emphasized the hero's successful achievements and gained popularity through the late Chosŏn dynasty. The Chinese and Korean allegories of heroic contributions emerged in response to complicated politics, as the Yuan government comprised multiple ethnic groups and the early Ming and early Chosŏn were newly established after the fall of previous dynasties. For the same reason, the hawk-hero allegory began to lose its relevance over time, and hawk paintings came to take on rather mundane meanings.
Coupling of dynamic microtubules to F-actin by Fmn2 regulates chemotaxis of neuronal growth cones
Authors: Kundu Tanushree , Dutta Priyanka , Nagar Dhriti , Maiti Sankar , Ghose Aurnab
Published: June 2021

Dynamic co-regulation of the actin and microtubule subsystems enables the highly precise and adaptive remodelling of the cytoskeleton necessary for critical cellular processes, such as axonal pathfinding. The modes and mediators of this interpolymer crosstalk, however, are inadequately understood. We identify Fmn2, a non-diaphanous-related formin associated with cognitive disabilities, as a novel regulator of cooperative actin–microtubule remodelling in growth cones of both chick and zebrafish neurons. We show that Fmn2 stabilizes microtubules in the growth cones of cultured spinal neurons and in vivo. Super-resolution imaging revealed that Fmn2 facilitates guidance of exploratory microtubules along actin bundles into the chemosensory filopodia. Using live imaging, biochemistry and single-molecule assays, we show that a C-terminal domain in Fmn2 is necessary for the dynamic association between microtubules and actin filaments. In the absence of the cross-bridging function of Fmn2, filopodial capture of microtubules is compromised, resulting in destabilized filopodial protrusions and deficits in growth cone chemotaxis. Our results uncover a critical function for Fmn2 in actin–microtubule crosstalk in neurons and demonstrate that the modulation of microtubule dynamics via associations with F-actin is central to directional motility.
Maintenance of complex I and its supercomplexes by NDUF-11 is essential for mitochondrial structure, function and health
Authors: Knapp-Wilson Amber , Pereira Gonçalo C. , Buzzard Emma , Ford Holly C. , Richardson Andrew , Corey Robin A. , Neal Chris , Verkade Paul , Halestrap Andrew P. , Gold Vicki A. M. , Kuwabara Patricia E. , Collinson Ian
Published: June 2021

Mitochondrial supercomplexes form around a conserved core of monomeric complex I and dimeric complex III; wherein a subunit of the former, NDUFA11, is conspicuously situated at the interface. We identified nduf-11 (B0491.5) as encoding the Caenorhabditis elegans homologue of NDUFA11. Animals homozygous for a CRISPR-Cas9-generated knockout allele of nduf-11 arrested at the second larval (L2) development stage. Reducing (but not eliminating) expression using RNAi allowed development to adulthood, enabling characterisation of the consequences: destabilisation of complex I and its supercomplexes and perturbation of respiratory function. The loss of NADH dehydrogenase activity was compensated by enhanced complex II activity, with the potential for detrimental reactive oxygen species (ROS) production. Cryo-electron tomography highlighted aberrant morphology of cristae and widening of both cristae junctions and the intermembrane space. The requirement of NDUF-11 for balanced respiration, mitochondrial morphology and development presumably arises due to its involvement in complex I and supercomplex maintenance. This highlights the importance of respiratory complex integrity for health and the potential for its perturbation to cause mitochondrial disease.

This article has an associated First Person interview with Amber Knapp-Wilson, joint first author of the paper.
Threshold of Relative Muscle Power Required to Rise from a Chair and Mobility Limitations and Disability in Older Adults
Authors: ALCAZAR JULIAN , ALEGRE LUIS M. , SUETTA CHARLOTTE , JÚDICE PEDRO B. , VAN ROIE EVELIEN , GONZÁLEZ-GROSS MARCELA , RODRÍGUEZ-MAÑAS LEOCADIO , CASAJÚS JOSE A. , MAGALHãES JOãO P. , NIELSEN BARBARA R. , GARCÍA-GARCÍA FRANCISCO J. , DELECLUSE CHRISTOPHE , SARDINHA LUIS B. , ARA IGNACIO
Published: June 2021

Purpose

Being able to rise from a chair is paramount for independent living and is strongly influenced by the ability of the lower limbs to exert mechanical power. This study assessed minimal thresholds of lower-limb relative muscle power required to perform the sit-to-stand (STS) task in older adults and its association with mobility limitations and disability.

Methods

A total of 11,583 older adults (age, 60–103 yr) participated in this investigation. The 5-rep and 30-s versions of the STS test were used to assess chair rising ability. Relative power was calculated by the STS muscle power test. The minimum thresholds of power required to perform the STS tests were derived from the minimum values (i.e., “floor” effect) reported in the power tests through regression analyses. Mobility limitations and disability in activities of daily living (ADL) were recorded.

Results

For the average older man and woman, the thresholds to complete five STS repetitions were 1.1 and 1.0 W·kg−1, respectively, whereas the thresholds to complete one STS repetition were 0.3 W·kg−1 in both sexes. These thresholds increased linearly with height (5- and 1-rep, respectively: +0.13 and +0.03 W·kg−1 per 10-cm increase; both P < 0.001) and did not differ by sex or testing condition (both P ≥ 0.259). All participants with relative power below the 5-rep threshold presented mobility limitations, and 51%–56% of women and 36%–49% of men also showed disability in ADL (all χ
2 ≥ 290.4; P < 0.001).

Conclusion

A minimum level of relative muscle power is required to rise from a chair independently, which depends on the individual height and is associated with increased mobility limitations and disability. This information will help interpret data yielded by the STS muscle power test and may contribute to the prevention and treatment of mobility limitations in older people.
Comparison between skeletal muscle and adipose tissue measurements with high-dose CT and low-dose attenuation correction CT of 18F-FDG PET/CT in elderly Hodgkin lymphoma patients: a two-centre validation
Authors: Albano Domenico , Camoni Luca , Rinaldi Roberto , Tucci Alessandra , Zilioli Vittorio Ruggero , Muzi Cristina , Ravanelli Marco , Farina Davide , Coppola Alessandra , Camalori Manuela , Giubbini Raffaele , Bertagna Francesco
Published: June 2021

Objectives:

High-dose CT (HDCT) is considered the gold-standard imaging for the measurements of skeletal muscle area (SMA), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and intramuscular adipose tissue (IMAT) areas in the abdomen. These parameters may reflect sarcopenia, which can have a prognostic impact in several oncological diseases. The aim of this study was to compare the agreement of measurements of SMA, VAT, SAT and IMAT areas between HDCT and low-dose CT (LDCT) of 18-fludeoxyglucose positron emission tomography (18F-FDG PET)/CT in elderly patients affected by Hodgkin lymphoma (HL).

Methods:

We retrospectively included 90 patients affected by HL who underwent baseline 18F-FDG-PET/CT and HDCT within a mean interval of 7 days. HDCT and LDCT images were analysed by two blinded observers using segmentation software (Slice-O-Matic, Tomovision) to quantify the areas. HDCT and LDCT measurements were compared using Bland–Altman plots and Passing-Bablock regression analyses. Pearson correlation coefficient (r) was used to correlate measurements from the two imaging modalities.

Results:

Comparison of HDCT and LDCT data demonstrated a strong correlation for measurement of VAT(r = 0.942, p < 0.0001), SAT (r = 0.894, p < 0.0001) and SMA (r = 0.934, p < 0.0001). Instead considering IMAT, correlation was good but less significant (r = 0.742). The mean difference between the two methods was found to be very small, with a difference of 1% for SAT,+6.1% for VAT,+2.5% for SMA and −1.9% for IMAT.

Conclusion:

LDCT of PET/CT is a safe, accurate and precise method for the measurements of skeletal muscle area, visceral and subcutaneous adipose tissue. Their measurements are reproducible and correlate closely with HDCT.

Advances in knowledge:

LLDCT of PET/CT is a safe and accurate method for the measurements of SMA, VAT and SAT; their measurements are closely correlated with HDCT. LDCT can be considered an accurate alternative tool for measuring abdominal fat and muscles in the clinical practice.
Pengaruh Crowes Fraud Pentagon dalam Mendeteksi Kecurangan Pelaporan Keuangan
Authors: Sapulette Shella Gilby , Risakotta Kathleen Asyera
Published: June 2021

This study aims to obtain empirical evidence and to examine the elements of fraud in fraud pentagon theory against indications of fraudulent financial reporting on 42 leasing companies  listed in the Indonesia stock exchange (BEI) period 2016-2018. Independent variables in this research were financial target, external pressure, ineffective monitoring, change in auditor, change of director, and frequent number of CEO’s picture, while the dependent variable was fraudulent financial reporting which measured using earnings management (DACC). This research use multiple linear regression method with 21 SPSS software. The results of this research shows that financial target, ineffective monitoring, and frequent number of CEO’s picture are significant in detecting fraudulent financial reporting. These variables represents three elements in fraud pentagon, namely pressure, opportunity and arrogance.
ANALISIS FAKTOR-FAKTOR YANG MEMPENGARUHI FINANCIAL DISTRESS PADA PERBANKAN YANG TERDAFTAR DI BURSA EFEK INDONESIA
Authors: Azis Safira Nurmalika , Rahardjo Shiddiq Nur
Published: June 2021

This study aims to examine whether financial ratios have an influence on financial distress. The dependent variable in this study is financial distress which is measured using a dummy variable. The independent variables in this study are CAR, NPL, ROA, ROE and capital structure. In addition, this study also uses the Altman model to determine the level of bankruptcy in banks This study also uses dummy variables to find out which banks are healthy and unhealthy. Hypothesis testing of this study was carried out using logistic regression analysis. This study provides statistical results that show that the CAR has a negative and significant effect on financial distress, ROA has a negative and significant effect on financial distress and the capital structure has a positive and significant effect on financial distress. Whereas NPL and ROE do not have an influence on financial distress.
PENGARUH DANA KAPITASI DALAM MENINGKATKAN KUALITAS LAYANAN PADA FASILITAS KESEHATAN TINGKAT PERTAMA DI YOGYAKARTA
Authors: Shofiyah Indah , Bastian Indra
Published: June 2021

This study aims to investigate the effect of capitation in improving the service quality at primary care in Yogyakarta province. Variables in this research are incentives and the proportion of capitation. This research use financial and performance primary care reports which collected from Health Agency in Yogyakarta Province. Data was successfully processed were 62 reports. The results of this research show that incentives and the proportion of capitation statistically influence in improving service quality, on the other side proportion of capitation funds statistically does not strengthen relationship between incentives and service quality.
Intermittent catheterisation: the common complications
Authors: Balhi Salma , Arfaouni Rym Baati , Mrabet Ali
Published: June 2021

Intermittent catheterisation (IC) has been in practice for more than 40 years and is considered the gold standard in the management of urinary retention in the neurological bladder. IC has many advantages over indwelling urethral or suprapubic catheterisation, including reducing the risk of infection, protecting the bladder and improving quality of life. However, complications can be caused by the practice of this technique, the most common of which is infection. This review discusses some of the common complications that can occur with the use of intermittent catheterisation, including urinary tract infection (UTIs) and urethral complications. It also highlights the role of the nurse in the management of its complications.
Use of breathable silicone technology in an ostomy appliance flange
Authors: Lager Peta , Loxdale Lisa
Published: June 2021

Leaks and peristomal skin complications are highly prevalent among people with a stoma, reported by over 80% of ostomates within 2 years of surgery. This suggests that there is room for improvement in ostomy appliances, particularly in their hydrocolloid-based adhesive flanges. Hydrocolloid has an absorptive method of moisture management that, over time, risks maceration and skin stripping, potentially leading to moisture-associated skin damage (MASD) and medical adhesive-related skin injury (MARSI). The newly developed Genii ostomy appliances (Trio Healthcare) use novel Sil2 Breathable Silicone Technology to provide secure, effective adhesion and manage moisture levels by replicating natural transepidermal water loss (TEWL). This has the potential to increase appliance wear time, reduce incidence of MASD and permit atraumatic removal without adhesive remover, reducing the risks of MARSI, as well as time burdens on the user and economic burdens on the healthcare system. Meanwhile, the silicone flanges and water-resistant sports fabric pouches are lightweight, flexible and unobtrusive, and they are the first appliances to be available in colours to match different skin tones, all of which provides security, comfort, confidence and discretion. This article explores the features of Sil2 and Genii ostomy appliances, with reference to preliminary data from a user evaluation.
Developments in silicone technology for use in stoma care
Authors: Swift Thomas , Westgate Gillian , Van Onselen Julie , Lee Stewart
Published: June 2021

Soft silicone's flexibility, adhesive capacity and non-toxic, non-odourous and hypoallergenic nature have made it an established material for adhesive and protective therapeutic devices. In wound care, silicone is a component of contact layer dressings for superficial wounds and silicone gel sheeting for reducing the risk of scarring, as well as of barriers for incontinence-associated dermatitis. Regarding stoma accessories, silicone is established in barrier films to prevent contact dermatitis, adhesive removers to prevent skin stripping and filler gels to prevent appliance leaks. Until recently, silicone has not been used in stoma appliances flanges, as its hydrophobic nature has not allowed for moisture management to permit transepidermal water loss and prevent maceration. Traditional hydrocolloid appliances manage moisture by absorbing water, but this can lead to saturation and moisture-associated skin damage (MASD), as well as increased adhesion and resultant skin tears on removal, known as medical adhesive-related skin injury (MARSI). However, novel silicone compounds have been developed with a distinct evaporation-based mechanism of moisture management. This uses colloidal separation to allow the passage of water vapour at a rate equivalent to normal transepidermal water loss. It has been shown to minimise MASD, increase wear time and permit atraumatic removal without the use of adhesive solvents. Trio Healthcare has introduced this technology with a range of silicone-based flange extenders and is working with the University of Bradford Centre for Skin Sciences on prototype silicone-based stoma appliance flanges designed to significantly reduce the incidence of peristomal skin complications, such as MARSI and MASD. It is hoped that this will also increase appliance wear time, reduce costs and improve patient quality of life.
Pixel crosstalk in naked-eye micro-LED 3D display
Authors: Xu Yi , Cui Jiawei , Hu Zelin , Gao Xiang , Wang Liancheng
Published: June 2021

Micro-LED display is considered to be the most promising display technology, and naked-eye 3D display represents the most advanced frontier of display. Naked-eye 3D micro-LED display has both the advantages of micro-LED display and the characteristics of naked-eye 3D display. Only conceptual solutions for 3D micro-LED display have been reported so far. The effect of luminescence distribution and the direction of micro-LED devices on crosstalk in the naked-eye 3D display is not clear. In this paper, we first investigated the chip-shaping effect on the emission characteristics, mainly the luminescence distribution and direction of the micro-LED, and then we investigated the influence of luminescence distribution and direction of micro-LED on the pixel crosstalk in naked-eye micro-LEDs 3D display. Our work should advance the micro-LED display, especially the micro-LED 3D display.
Optimizing mitochondrial maintenance in extended neuronal projections
Authors: Agrawal Anamika , Koslover Elena F.
Published: June 2021

Neurons rely on localized mitochondria to fulfill spatially heterogeneous metabolic demands. Mitochondrial aging occurs on timescales shorter than the neuronal lifespan, necessitating transport of fresh material from the soma. Maintaining an optimal distribution of healthy mitochondria requires an interplay between a stationary pool localized to sites of high metabolic demand and a motile pool capable of delivering new material. Interchange between these pools can occur via transient fusion / fission events or by halting and restarting entire mitochondria. Our quantitative model of neuronal mitostasis identifies key parameters that govern steady-state mitochondrial health at discrete locations. Very infrequent exchange between stationary and motile pools optimizes this system. Exchange via transient fusion allows for robust maintenance, which can be further improved by selective recycling through mitophagy. These results provide a framework for quantifying how perturbations in organelle transport and interactions affect mitochondrial homeostasis in neurons, a key aspect underlying many neurodegenerative disorders.
The prevalence of the Val66Met polymorphism in musicians: Possible evidence for compensatory neuroplasticity from a pilot study
Authors: Henechowicz Tara L. , Chen Joyce L. , Cohen Leonardo G. , Thaut Michael H.
Published: June 2021

The study compared the prevalence of the Val66Met Brain-derived Neurotrophic Factor single nucleotide polymorphism (rs6265) in a sample of musicians (N = 50) to an ethnically matched general population sample from the 1000 Human Genome Project (N = 424). Met-carriers of the polymorphism (Val/Met and Met/Met genotypes) are typically present in 25–30% of the general population and have associated deficits in motor learning and plasticity. Many studies have assessed the benefits of long-term music training for neuroplasticity and motor learning. This study takes a unique genetic approach investigating if the prevalence of the Val66Met BDNF polymorphism, which negatively affects motor learning, is significantly different in musicians from the general population. Our genotype and allele frequency analyses revealed that the distribution of the Val66Met polymorphism was not significantly different in musicians versus the general population (p = 0.6447 for genotype analysis and p = 0.8513 allele analysis). In the Musician sample (N = 50), the prevalence of the Val/Met genotype was 40% and the prevalence of the Met/Met genotype was 2%. In the 1000 Human Genome Project subset (N = 424), the prevalence of Val/Met was 33.25% and the Met/Met genotype prevalence was 4%. Therefore, musicians do exist with the Val66Met polymorphism and the characteristics of long-term music training may compensate for genetic predisposition to motor learning deficits. Since the polymorphism has significant implications for stroke rehabilitation, future studies may consider the implications of the polymorphism in music-based interventions such as Neurologic Music Therapy.