bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric Liddle Syndrome Caused by a Novel SCNN1G Variant in a Chinese Family and Characterized by Early-Onset Hypertension
Authors: Fan Peng , Pan Xiao-Cheng , Zhang Di , Yang Kun-Qi , Zhang Ying , Tian Tao , Luo Fang , Ma Wen-Jun , Liu Ya-Xin , Wang Lin-Ping , Zhang Hui-Min , Song Lei , Cai Jun , Zhou Xian-Liang
Published: March 2020

BACKGROUND

Liddle syndrome (LS), an autosomal dominant disorder, is a common monogenic hypertension in pediatrics. In this study, we reported a novel SCNN1G variant in a Chinese family with pediatric LS, and conduct a systematic review of epithelial sodium channel (ENaC)-gene-positive LS cases to conclude the clinical genetic features of LS in childhood.

METHODS

Next-generation sequencing and in silico analysis were performed in the proband to discover candidate variants. Sanger sequencing was used to identify the predicted likely pathogenic variant. LS patients in this family were treated with amiloride. The Medline database was searched to summarize clinical features of pediatric LS cases whose age at genetic diagnosis was not more than 18 years.

RESULTS

Genetic analysis identified a novel SCNN1G missense variant (c.1874C>T, p.Pro625Leu) in the proband with LS in childhood. In silico analysis revealed this heterozygous variant was highly conserved and deleterious. A total of 38 publications described pediatric LS associated with 25 pathogenic variants in SCNN1B and SCNN1G in 54 children. Despite the phenotypic heterogeneity, early-onset hypertension is the most common feature. All LS patients in this family or the reviewed cases showed significantly improvements in hypertension and hypokalemia after treatment with ENaC inhibitors.

CONCLUSIONS

This study identified a novel SCNN1G missense variant in a patient with pediatric LS, expanding the genetic spectrum of SCNN1G and demonstrating the PY motif of γ-ENaC as a potential mutant region. Early identification and specific management of LS in children and adolescents are important to prevent the development of hypertensive end-organ disease.
Long-term effects of elevated CO2, nighttime warming and drought on plant secondary metabolites in a temperate heath ecosystem
Authors: Li Tao , Tiiva Päivi , Rinnan Åsmund , Julkunen-Tiitto Riitta , Michelsen Anders , Rinnan Riikka
Published: March 2020

Background and Aims

Plant secondary metabolites play critical roles in plant stress tolerance and adaptation, and are known to be influenced by the environment and climate changes, yet the impacts and interactions of multiple climate change components are poorly understood, particularly under natural conditions.

Methods

Accumulation of phenolics and emissions of volatile organic compounds (VOCs) were assessed on heather, Calluna vulgaris, an abundant evergreen dwarf shrub in European heathlands, after 6 years of exposure to elevated CO2, summer drought and nighttime warming.

Key Results

Drought alone had the strongest effects on phenolic concentrations and compositions, with moderate effects of elevated CO2 and temperature. Elevated CO2 exerted the greatest impact on VOC emissions, mainly by increasing monoterpene emissions. The response magnitudes varied among plant tissue types and chemical constituents, and across time. With respect to interactive effects of the studied climate change components, the interaction between drought and elevated CO2 was most apparent. Drought mainly reduced phenolic accumulation and VOC emissions, while elevated CO2 mitigated such effects.

Conclusions

In natural ecosystems, co-occurring climate factors can exert complex impacts on plant secondary metabolite profiles, which may in turn alter ecosystem processes.
Introduction to the Special Issue: The role of seed dispersal in plant populations: perspectives and advances in a changing world
Authors: Beckman Noelle G , Aslan Clare E , Rogers Haldre S
Published: March 2020

Despite the importance of seed dispersal as a driving process behind plant community assembly, our understanding of the role of seed dispersal in plant population persistence and spread remains incomplete. As a result, our ability to predict the effects of global change on plant populations is hampered. We need to better understand the fundamental link between seed dispersal and population dynamics in order to make predictive generalizations across species and systems, to better understand plant community structure and function, and to make appropriate conservation and management responses related to seed dispersal. To tackle these important knowledge gaps, we established the CoDisperse Network and convened an interdisciplinary, NSF-sponsored Seed Dispersal Workshop in 2016, during which we explored the role of seed dispersal in plant population dynamics (NSF DEB Award # 1548194). In this Special Issue, we consider the current state of seed dispersal ecology and identify the following collaborative research needs: (i) the development of a mechanistic understanding of the movement process influencing dispersal of seeds; (ii) improved quantification of the relative influence of seed dispersal on plant fitness compared to processes occurring at other life history stages; (iii) an ability to scale from individual plants to ecosystems to quantify the influence of dispersal on ecosystem function; and (iv) the incorporation of seed dispersal ecology into conservation and management strategies.
LexITA: A Quick and Reliable Assessment Tool for Italian L2 Receptive Vocabulary Size
Authors: Amenta Simona , Badan Linda , Brysbaert Marc
Published: March 2020

In language and second language acquisition research, it is important to have a measure for tracking the proficiency level of participants. Lexical competence is fundamental for communicative purposes in a given language, and vocabulary tests are a reliable measure to assess lexical proficiency. That is why vocabulary tests have a central role in language proficiency assessment. Although many people study Italian as second language (L2), an easy-to-use vocabulary test to measure lexical proficiency is still missing. In this work, we aim to fill this gap by presenting LexITA, which is an objective, reliable, and quick assessment of Italian receptive vocabulary. LextITA was validated on students of Italian L2 and showed to be a valid measure to assess vocabulary knowledge of L2 speakers spanning different levels of proficiency.
Sex-specific effects of developmental temperature on morphology, growth and survival of offspring in a lizard with temperature-dependent sex determination
Authors: Steele Ariel L , Warner Daniel A
Published: March 2020

The developmental environment plays a pivotal role in shaping fitness-relevant phenotypes of all organisms. Phenotypes are highly labile during embryogenesis, and environmental factors experienced early in development can have profound effects on fitness-relevant traits throughout life. Many reptiles exhibit temperature-dependent sex determination (TSD), whereby temperature during embryonic development permanently determines offspring sex. The leading hypothesis for the adaptive significance of TSD posits that egg incubation temperature differentially affects the fitness of males vs. females so that each sex is produced at its optimal temperature. The goal of this research is to address this hypothesis by quantifying the sex-specific effects of incubation temperature on phenotypes and survival in a lizard (Agama picticauda) with TSD. By incubating eggs under constant and fluctuating temperatures, we demonstrated that incubation temperature affects fitness-relevant phenotypes in A. picticauda; but males and females had similar reaction norms. However, females produced from female-biased incubation temperatures had greater survival than those from male-biased temperatures, and male survival was lowest for individuals produced from a female-biased temperature. In addition, eggs incubated at male-biased temperatures hatched earlier than those incubated at female-biased temperatures, which may have sex-specific consequences later in life as predicted by models for the adaptive significance of TSD.
A simple index to quantify and compare the magnitude of intraspecific geographic plumage colour variation in typical antbirds (Aves: Passeriformes: Thamnophilidae)
Authors: Marcondes Rafael S , Brumfield Robb T
Published: March 2020

Intraspecific geographic phenotypic variation is a crucial theme in evolutionary biology. Comparing its magnitude across species can provide insights into its ecological and genetic correlates. Here, we developed an index, which we dub the V index, to quantify intraspecific plumage colour variation in typical antbirds (Thamnophilidae), a family which has long interested ornithologists due to a high prevalence of intraspecific variation. The V index is based on a bivariate colour space defined by brightness and redness. Its value for each species equals the mean area occupied by each of its subspecies in that colour space, divided by the area of the species. Lower values indicate greater intraspecific geographic variation. Based on this index, Thamnophilus caerulescens (Variable Antshrike) was exceptionally geographically variable compared to other thamnophilids, as previously suggested based on qualitative evidence. In general, we found that the most variable species had disjunct distributions and deep phylogeographic structure, suggesting an effect of historical population dynamics in producing geographic variation. The V index can be adapted for use with other taxa, traits, and taxonomic levels, and we expect it will instigate novel ways of thinking about phenotypic variation in birds and other animals.
How to Engage in Illegal Transactions: Resolving Risk and Uncertainty in Corrupt Dealings
Authors: Wang Peng
Published: March 2020

How do exchange participants address risk in illegal transactions? The socio-cultural literature examines risk from cultural, ‘risk society’ and ‘governmentality’ perspectives, but there is relatively little empirical work focusing on the ways in which people experience and handle risk in illegal markets. Drawing on insights from criminology, economic sociology and social psychology, this article aims to contribute to the study of risk and uncertainty under conditions of illegality. It investigates a popular type of corrupt exchange in China: the buying and selling of government positions that are embedded in the power-imbalanced patron–client relation. The article examines the difference in risk faced by buyers and sellers and explores how they manage these transaction risks without resorting to state protection mechanisms (e.g. the police and courts). The article is based on 61 in-depth interviews with academics, journalists and state officials and a review of official documents and news reports in Chinese and English.
Practitioner Emotions in Penal Voluntary Sectors: Experiences from England and Canada
Authors: Tomczak Philippa , Quinn Kaitlyn
Published: March 2020

Mixed economies of welfare have seen increasing numbers of service users funnelled into voluntary, rather than statutory sector services. Many service users with (complex) human needs now fall within the remit of ill-researched voluntary organisations that are rarely social work led. Voluntary sector practitioners comprise a large and rising proportion of the social services workforce, but their experiences have received minimal analysis. Despite the importance of emotions across the helping professions, voluntary sector practitioners’ emotional experiences are largely unknown. We address this gap, using an innovative bricolage of original qualitative data from England and Canada to highlight how ‘emotions matter for penal voluntary sector (PVS) practitioners across diverse organisational roles, organisational contexts, and national jurisdictions’. We examine the emotions of paid and volunteer PVS practitioners relating to their (i) organisational contexts and (ii) relationships with criminalised service users. Problematising positive, evocative framings of ‘citizen participation’, we argue that continuing to overlook voluntary sector practitioners’ emotions facilitates the downloading of double neo-liberal burdens—‘helping’ marginalised populations and generating the funds to do so—onto individual practitioners, who are too often ill-equipped to manage them.
Distinct patterns of structural damage underlie working memory and reasoning deficits after traumatic brain injury
Authors: Jolly Amy E , Scott Gregory T , Sharp David J , Hampshire Adam H
Published: March 2020

It is well established that chronic cognitive problems after traumatic brain injury relate to diffuse axonal injury and the consequent widespread disruption of brain connectivity. However, the pattern of diffuse axonal injury varies between patients and they have a correspondingly heterogeneous profile of cognitive deficits. This heterogeneity is poorly understood, presenting a non-trivial challenge for prognostication and treatment. Prominent amongst cognitive problems are deficits in working memory and reasoning. Previous functional MRI in controls has associated these aspects of cognition with distinct, but partially overlapping, networks of brain regions. Based on this, a logical prediction is that differences in the integrity of the white matter tracts that connect these networks should predict variability in the type and severity of cognitive deficits after traumatic brain injury. We use diffusion-weighted imaging, cognitive testing and network analyses to test this prediction. We define functionally distinct subnetworks of the structural connectome by intersecting previously published functional MRI maps of the brain regions that are activated during our working memory and reasoning tasks, with a library of the white matter tracts that connect them. We examine how graph theoretic measures within these subnetworks relate to the performance of the same tasks in a cohort of 92 moderate-severe traumatic brain injury patients. Finally, we use machine learning to determine whether cognitive performance in patients can be predicted using graph theoretic measures from each subnetwork. Principal component analysis of behavioural scores confirm that reasoning and working memory form distinct components of cognitive ability, both of which are vulnerable to traumatic brain injury. Critically, impairments in these abilities after traumatic brain injury correlate in a dissociable manner with the information-processing architecture of the subnetworks that they are associated with. This dissociation is confirmed when examining degree centrality measures of the subnetworks using a canonical correlation analysis. Notably, the dissociation is prevalent across a number of node-centric measures and is asymmetrical: disruption to the working memory subnetwork relates to both working memory and reasoning performance whereas disruption to the reasoning subnetwork relates to reasoning performance selectively. Machine learning analysis further supports this finding by demonstrating that network measures predict cognitive performance in patients in the same asymmetrical manner. These results accord with hierarchical models of working memory, where reasoning is dependent on the ability to first hold task-relevant information in working memory. We propose that this finer grained information may be useful for future applications that attempt to predict long-term outcomes or develop tailored therapies.
Predicting incidences of neurodevelopmental disorders
Authors: Lemke Johannes R
Published: March 2020

This scientific commentary refers to ‘A catalogue of new incidence estimates of monogenic neurodevelopmental disorders caused by de novo variants’ by López-Rivera etal. (doi:10.1093/brain/awaa051).
Localization of Brain Networks Engaged by the Sustained Attention to Response Task Provides Quantitative Markers of Executive Impairment in Amyotrophic Lateral Sclerosis
Authors: McMackin Roisin , Dukic Stefan , Costello Emmet , Pinto-Grau Marta , Fasano Antonio , Buxo Teresa , Heverin Mark , Reilly Richard , Muthuraman Muthuraman , Pender Niall , Hardiman Orla , Nasseroleslami Bahman
Published: March 2020

Objective: To identify cortical regions engaged during the sustained attention to response task (SART) and characterize changes in their activity associated with the neurodegenerative condition amyotrophic lateral sclerosis (ALS). Methods: High-density electroencephalography (EEG) was recorded from 33 controls and 23 ALS patients during a SART paradigm. Differences in associated event-related potential peaks were measured for Go and NoGo trials. Sources active during these peaks were localized, and ALS-associated differences were quantified. Results: Go and NoGo N2 and P3 peak sources were localized to the left primary motor cortex, bilateral dorsolateral prefrontal cortex (DLPFC), and lateral posterior parietal cortex (PPC). NoGo trials evoked greater bilateral medial PPC activity during N2 and lesser left insular, PPC and DLPFC activity during P3. Widespread cortical hyperactivity was identified in ALS during P3. Changes in the inferior parietal lobule and insular activity provided very good discrimination (AUROC > 0.75) between patients and controls. Activation of the right precuneus during P3 related to greater executive function in ALS, indicative of a compensatory role. Interpretation: The SART engages numerous frontal and parietal cortical structures. SART–EEG measures correlate with specific cognitive impairments that can be localized to specific structures, aiding in differential diagnosis.
In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Authors: Yao Xueting , Ye Fei , Zhang Miao , Cui Cheng , Huang Baoying , Niu Peihua , Liu Xu , Zhao Li , Dong Erdan , Song Chunli , Zhan Siyan , Lu Roujian , Li Haiyan , Tan Wenjie , Liu Dongyang
Published: March 2020

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in 2019 and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late phase in critically ill patients with SARS-CoV-2. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection.

Methods

The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2–infected Vero cells. Physiologically based pharmacokinetic (PBPK) models were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen while considering the drug’s safety profile.

Results

Hydroxychloroquine (EC50 = 0.72 μM) was found to be more potent than chloroquine (EC50 = 5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached 3 times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance.

Conclusions

Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.
Amylolysis of a chromogenic substrate, Cibachron Blue F3GA-amylose: kinetics and mechanism.
Authors: Klein B , Foreman J A
Published: March 2020

We compared the modes of action of human pancreatic, human salivary, and porcine pancreatic amylases on Cibachron Blue F3GA-amylose. Both human enzymes showed similar catalytic activity with almost equal Vmax but dissimilar apparent Km's. The ratios of soluble dyed oligosaccharides to reducing substances were identical. Porcine pancreatic amylase exhibited less than half the Vmax of the human enzymes and a smaller apparent Km. Reducing substances were formed faster than were the soluble dyed products. These differences in amylolytic action can be explained by differences in the degree of the “multiple attack" mechanism. Introduction of dye substituents into the amylose molecule did not alter the substrate characteristics of amylose toward human serum amylase.
Ecosystem services provided by Neotropical birds
Authors: Michel Nicole L , Whelan Christopher J , Verutes Gregory M
Published: March 2020

The Millennium Ecosystem Assessment described 4 classes of services or functions that ecosystems and their component parts deliver to the benefit of humans: provisioning, regulating, supporting, and cultural services. Birds, including Neotropical birds, provide a diverse array of services in all 4 classes. We review the literature describing ecosystem services provided by Neotropical birds, draw inference from studies of avian services in other regions when Neotropical studies are limited, and identify key information gaps. Neotropical birds provide provisioning services in the form of meat and eggs for food, and feathers for down and ornamentation. Regulating services are among the most valuable services provided by Neotropical birds, including pollination, pest control, seed dispersal, and scavenging. Neotropical birds also provide supporting services in the form of nutrient cycling, such as through the deposition of guano on offshore islands. Finally, Neotropical birds provide cultural services as pets (caged birds), sources of recreation (e.g., birdwatching, hunting), as well as by inspiring art, photography, and religious customs. Much remains to be learned about the ecology and natural history of many Neotropical birds before we can fully assign value—monetary, nonmaterial, or otherwise—to the services they provide. However, what we have learned to date makes it clear that humans benefit from birds through multiple services, including but not limited to pest reduction, pollination of some agricultural plants, and seed dispersal.
Association of Faecal Calprotectin Level and Combined Endoscopic and Radiological Healing in Patients With Crohn’s Disease Receiving Anti-tumour Necrosis Factor Therapy
Authors: Noh Soo Min , Oh Eun Hye , Park Seong Ho , Lee Jung Bok , Kim Jin Yong , Park Jae Cheol , Kim Jeongseok , Ham Nam Seok , Hwang Sung Wook , Park Sang Hyoung , Yang Dong-Hoon , Byeon Jeong-Sik , Myung Seung-Jae , Yang Suk-Kyun , Ye Beyong Duk
Published: March 2020

Background and Aims

Combined endoscopic and radiological healing, or deep healing, is associated with favourable outcomes in patients with Crohn’s disease; thus, a non-invasive biomarker for predicting deep healing would be invaluable. We evaluated the usefulness of faecal calprotectin for predicting deep healing in patients with Crohn’s disease receiving anti-tumour necrosis factor [TNF] therapy.

Methods

We analysed the records of patients with Crohn’s disease who received anti-tumour necrosis factor therapy and underwent endoscopic evaluation, radiological evaluation, and faecal calprotectin measurement within a period of 3 months between August 2017 and November 2018. Results of endoscopic and radiological studies were independently reviewed by two gastrointestinal endoscopists and a gastrointestinal radiologist, respectively. Serum C-reactive protein and albumin were also measured.

Results

Out of 268 patients analysed, 77 [28.7%] had deep healing, 36 [13.4%] had endoscopic healing only, 36 [13.4%] had radiological healing only, and 119 [44.4%] had neither. The median duration of anti-TNF treatment was 40.0 months. The deep healing group had the lowest median faecal calprotectin level [56.5 mg/kg] among the four groups [p <0.001]. The faecal calprotectin cutoff level of 81.1 mg/kg showed a sensitivity of 0.623 and a specificity of 0.817 in predicting deep healing (area under the receiver operating characteristic curve [AUROC], 0.767; 95% confidence interval, 0.702–0.832). Adding serum C-reactive protein and serum albumin to faecal calprotectin further increased the AUROC to 0.805 [95% confidence interval, 0.752–0.858].

Conclusions

Faecal calprotectin, when combined with serum C-reactive protein and albumin, showed acceptable performance in predicting deep healing in patients with Crohn’s disease.
Genome reconstruction reveals distinct assemblages of Gallionellaceae in surface and subsurface redox transition zones
Authors: Bethencourt Lorine , Bochet Olivier , Farasin Julien , Aquilina Luc , Borgne Tanguy Le , Quaiser Achim , Biget Marine , Michon-Coudouel Sophie , Labasque Thierry , Dufresne Alexis
Published: March 2020

Fe-oxidizing bacteria of the family Gallionellaceae are major players in the Fe biogeochemical cycle in freshwater. These bacteria thrive in redox transition zones where they benefit from both high Fe concentrations and microaerobic conditions. We analysed the Gallionellaceae genomic diversity in an artesian hard-rock aquifer where redox transition zones develop (i) in the subsurface, where ancient, reduced groundwater mixes with recent oxygenated groundwater, and (ii) at the surface, where groundwater reaches the open air. A total of 15 new draft genomes of Gallionellaceae representing to 11 candidate genera were recovered from the two redox transition zones. Sulfur oxidation genes were encoded in most genomes while denitrification genes were much less represented. One genus dominated microbial communities belowground and we propose to name it ‘Candidatus Houarnoksidobacter’. The two transition zones were populated by completely different assemblages of Gallionellaceae despite the almost constant upward circulation of groundwater between the two zones. The processes leading to redox transition zones, oxygen diffusion at the surface or groundwater mixing in subsurface, appear to be a major driver of the Gallionellaceae diversity.
The General Self-Efficacy of Older Adults Receiving Care: A Systematic Review and Meta-Analysis
Authors: Whitehall Lucy , Rush Robert , Górska Sylwia , Forsyth Kirsty
Published: March 2020

Background and Objectives

General self-efficacy (GSE) encourages health-promoting behaviors in older adults. It is unsurprising then that older adults receiving health care services are reported to have a greater risk of low GSE than older adults who are not. Despite this, there is currently limited evidence investigating whether the effect differs based on the environment in which care is received. This review aims to determine whether the GSE of older adults is affected by the receipt of health care services and whether GSE varies based on the setting in which care is received.

Research Design and Methods

In accordance with PRISMA guidelines (PROSPERO registration number CRD42018092191), a systematic search was undertaken across 7 databases. Standardized mean differences (SMD) and mean General Self-Efficacy Scale scores, with 95% confidence intervals (CI), were pooled for meta-analysis.

Results

A total of 40 studies were identified, they consisted of 33 population cohorts that were included in the meta-analysis. Older adults receiving health care services were found to be at greater risk of having lower GSE than those who do not (SMD = −0.62; 95% CI: −0.96 to −0.27, p < .0001). Following identification of sources of heterogeneity, older adults receiving acute inpatient care were more likely to have lower GSE than those receiving care in other health care settings.

Discussion and Implications

Older adults receiving inpatient care have a greater risk of lower GSE, and consequently, poorer health-promoting behaviors. Further research is recommended that focuses on the GSE of older adults and health outcomes following discharge from inpatient care.
Evaluation of a pair-based, joint-likelihood association approach for regional infrasound event identification
Authors: Blom Philip , Euler Garrett , Marcillo Omar , Dannemann Dugick Fransiska
Published: March 2020

A Bayesian framework for the association of infrasonic detections is presented and evaluated for analysis at regional propagation scales. A pair-based, joint-likelihood association approach is developed that identifies events by computing the probability that individual detection pairs are attributable to a hypothetical common source and applying hierarchical clustering to identify events from the pair-based analysis. The framework is based on a Bayesian formulation introduced for infrasonic source localization and utilizes the propagation models developed for that application with modifications to improve the numerical efficiency of the analysis. Clustering analysis is completed using hierarchical analysis via weighted linkage for a non-Euclidean distance matrix defined by the negative log-joint-likelihood values. The method is evaluated using regional synthetic data with propagation distances of hundreds of kilometres in order to study the sensitivity of the method to uncertainties and errors in backazimuth and time of arrival. The method is found to be robust and stable for typical uncertainties, able to effectively distinguish noise detections within the data set from those in events, and can be made numerically efficient due to its ease of parallelization.
Effects of anxiety on preferences for generic medicines in Australia
Authors: Barton Belinda L , Burke Paul F , Waller David S
Published: March 2020

Generic medicines have been available to consumers for ∼40 years, with varying degrees of uptake in different countries. Despite offering equivalent therapeutic qualities, generic medicines still struggle to be accepted by consumers. This study examines the role of a consumer’s affective state and framing effects on the purchase of a branded versus a generic pharmaceutical product. These issues are examined in an experiment, with independent manipulations of consumer anxiety levels and the framing of generic alternatives by the pharmacist. The sample comprised 426 men and women within Australia who completed an online survey with a scenario of purchasing a pharmaceutical after visiting a General Practitioner. Results indicate that those consumers experiencing higher levels of anxiety and where the doctor prescribed the branded medicine are more likely to choose branded medicines over cheaper, generic alternatives. The effect of framing the generic alternative as either ‘generic’ or ‘cheaper’ was not significant.
Effect of income inequality, community infrastructure and individual stressors on adult depression
Authors: Fan Vanessa Sha , Mahadevan Renuka , Leung Janni
Published: March 2020

This paper considers the impact of variables at three different levels—city, community and individual—on the depression of adults aged 45 years and above in China. Evidence shows that community factors, such as infrastructure and elderly centres, are critical to reduce depression but the effect of city-level factors such as lowering income inequality and improving public health investment is different for the segments of poor and non-poor as well as the rural and urban residents. This highlights the need to consider targeted policy mix options to avoid resource misallocation. Lastly, Chinese females’ depression has worsened over time with ageing, particularly those who drink alcohol or are less educated are prone to depression prompting the need for specialist women health centres.
Steering Teens Safe: translation to a workplace wellness program in the USA
Authors: Harland Karisa K , Yang Jingzhen Ginger , Peek-Asa Corinne
Published: March 2020

Parent-based teen driving interventions have been shown to increase safe teen driving but few have been translated beyond the research setting. As employers focus more on total worker health, the workplace offers a unique opportunity to implement a safe teen driving program into a workplace wellness program. The aim of this study was to adapt the evidence-based, parent-focused teen safe driving program Steering Teens Safe (STS) into workplace wellness programs, and to evaluate the implementation process and effect on parent–teen communication. The Replicating Effective Programs framework was used to modify STS to fit the workplace setting. The implementation process of the STS workplace wellness program was measured using direct observation and recordings of parent communication trainings while the effectiveness was measured by parent questionnaires. Forty-five parent employees across three businesses participated in the study. STS trainers were skilled in training parents in effective communication, including using open-ended questions and reflections. Parents reported increased success in conversations with their teens regarding safe driving through increased affection, receptivity, trust and equality in conversations. Workplaces may play a key role in assisting parents with teaching their children about safe driving.
DHTKD1 and OGDH display substrate overlap in cultured cells and form a hybrid 2-oxo acid dehydrogenase complex in vivo
Authors: Leandro João , Dodatko Tetyana , Aten Jan , Nemeria Natalia S , Zhang Xu , Jordan Frank , Hendrickson Ronald C , Sanchez Roberto , Yu Chunli , DeVita Robert J , Houten Sander M
Published: March 2020

Glutaric aciduria type 1 (GA1) is an inborn error of lysine degradation characterized by a specific encephalopathy that is caused by toxic accumulation of lysine degradation intermediates. Substrate reduction through inhibition of DHTKD1, an enzyme upstream of the defective glutaryl-CoA dehydrogenase, has been investigated as a potential therapy, but revealed the existence of an alternative enzymatic source of glutaryl-CoA. Here, we show that loss of DHTKD1 in glutaryl-CoA dehydrogenase-deficient HEK-293 cells leads to a 2-fold decrease in the established GA1 clinical biomarker glutarylcarnitine and demonstrate that oxoglutarate dehydrogenase (OGDH) is responsible for this remaining glutarylcarnitine production. We furthermore show that DHTKD1 interacts with OGDH, dihydrolipoyl succinyltransferase and dihydrolipoamide dehydrogenase to form a hybrid 2-oxoglutaric and 2-oxoadipic acid dehydrogenase complex. In summary, 2-oxoadipic acid is a substrate for DHTKD1, but also for OGDH in a cell model system. The classical 2-oxoglutaric dehydrogenase complex can exist as a previously undiscovered hybrid containing DHTKD1 displaying improved kinetics towards 2-oxoadipic acid.
Rapid Shifts in the Temperature Dependence of Locomotor Performance in an Invasive Frog,Xenopus laevis, Implications for Conservation
Authors: Araspin Laurie , Martinez Anna Serra , Wagener Carla , Courant Julien , Louppe Vivien , Padilla Pablo , Measey John , Herrel Anthony
Published: March 2020

Temperature is a critical abiotic factor impacting all aspects of the biology of organisms, especially in ectotherms. As such, it is an important determinant of the potential invasive ability of organisms and may limit population expansion unless organisms can physiologically respond to changes in temperature either through plasticity or by adapting to their novel environment. Here, we studied the African clawed frog, Xenopus laevis, which has become invasive on a global scale. We compared adults from an invasive population of western France with individuals from two populations in the native range in South Africa. We measured the thermal dependence of locomotor performance in adults given its relevance to dispersal, predator escape, and prey capture. Our results show significant differences in the limits of the 80% performance breadth interval for endurance with the French population showing a left shift in its limits congruent with the colder climate experienced in France. The French invasive population was introduced only about 40 years ago suggesting a rapid shift in the thermal physiology. Given that all individuals were acclimated under laboratory conditions at 23°C for 2 months this suggests that the invasive frogs have adapted to their new environment. These data may allow the refinement of physiologically informed species distribution models permitting better estimates of future ranges at risk of invasion.
Cleft lip/palate and educational attainment: cause, consequence or correlation? A Mendelian randomization study
Authors: Dardani Christina , Howe Laurence J , Mukhopadhyay Nandita , Stergiakouli Evie , Wren Yvonne , Humphries Kerry , Davies Amy , Ho Karen , Weinberg Seth M , Marazita Mary L , Mangold Elisabeth , Ludwig Kerstin U , Relton Caroline L , Davey Smith George , Lewis Sarah J , Sandy Jonathan , Davies Neil M , Sharp Gemma C
Published: March 2020

Background

Previous studies have found that children born with a non-syndromic orofacial cleft have lower-than-average educational attainment. Differences could be due to a genetic predisposition to low intelligence and academic performance, factors arising due to the cleft phenotype (such as social stigmatization, impaired speech/language development) or confounding by the prenatal environment. A clearer understanding of this mechanism will inform interventions to improve educational attainment in individuals born with a cleft, which could substantially improve their quality of life. We assessed evidence for the hypothesis that common variant genetic liability to non-syndromic cleft lip with or without cleft palate (nsCL/P) influences educational attainment.

Methods

We performed a genome-wide association study (GWAS) meta-analysis of nsCL/P with 1692 nsCL/P cases and 4259 parental and unrelated controls. Using GWAS summary statistics, we performed Linkage Disequilibrium (LD)-score regression to estimate the genetic correlation between nsCL/P, educational attainment (GWAS n = 766 345) and intelligence (GWAS n = 257 828). We used two-sample Mendelian randomization to evaluate the causal effects of genetic liability to nsCL/P on educational attainment and intelligence.

Results

There was limited evidence for shared genetic aetiology or causal relationships between nsCL/P and educational attainment [genetic correlation (rg) −0.05, 95% confidence interval (CI) −0.12 to 0.01, P 0.13; MR estimate (βMR) −0.002, 95% CI −0.009 to 0.006, P 0.679) or intelligence (rg −0.04, 95% CI −0.13 to 0.04, P 0.34; βMR −0.009, 95% CI −0.02 to 0.002, P 0.11).

Conclusions

Common variants are unlikely to predispose individuals born with nsCL/P to low educational attainment or intelligence. This is an important first step towards understanding the aetiology of low educational attainment in this group.
Avian Influenza Human Infections at the Human-Animal Interface
Authors: Philippon Damien A M , Wu Peng , Cowling Benjamin J , Lau Eric H Y
Published: March 2020

Background

Avian influenza A viruses (AIVs) are among the most concerning emerging and re-emerging pathogens because of the potential risk for causing an influenza pandemic with catastrophic impact. The recent increase in domestic animals and poultry worldwide was followed by an increase of human AIV outbreaks reported.

Methods

We reviewed the epidemiology of human infections with AIV from the literature including reports from the World Health Organization, extracting information on virus subtype, time, location, age, sex, outcome, and exposure.

Results

We described the characteristics of more than 2500 laboratory-confirmed human infections with AIVs. Human infections with H5N1 and H7N9 were more frequently reported than other subtypes. Risk of death was highest among reported cases infected with H5N1, H5N6, H7N9, and H10N8 infections. Older people and males tended to have a lower risk of infection with most AIV subtypes, except for H7N9. Visiting live poultry markets was mostly reported by H7N9, H5N6, and H10N8 cases, while exposure to sick or dead bird was mostly reported by H5N1, H7N2, H7N3, H7N4, H7N7, and H10N7 cases.

Conclusions

Understanding the profile of human cases of different AIV subtypes would guide control strategies. Continued monitoring of human infections with AIVs is essential for pandemic preparedness.
Addressing Ethical Challenges in US-Based HIV Phylogenetic Research
Authors: Dawson Liza , Benbow Nanette , Fletcher Faith E , Kassaye Seble , Killelea Amy , Latham Stephen R , Lee Lisa M , Leitner Thomas , Little Susan J , Mehta Sanjay R , Martinez Omar , Minalga Brian , Poon Art , Rennie Stuart , Sugarman Jeremy , Sweeney Patricia , Torian Lucia V , Wertheim Joel O
Published: March 2020

In recent years, phylogenetic analysis of HIV sequence data has been used in research studies to investigate transmission patterns between individuals and groups, including analysis of data from HIV prevention clinical trials, in molecular epidemiology, and in public health surveillance programs. Phylogenetic analysis can provide valuable information to inform HIV prevention efforts, but it also has risks, including stigma and marginalization of groups, or potential identification of HIV transmission between individuals. In response to these concerns, an interdisciplinary working group was assembled to address ethical challenges in US-based HIV phylogenetic research. The working group developed recommendations regarding (1) study design; (2) data security, access, and sharing; (3) legal issues; (4) community engagement; and (5) communication and dissemination. The working group also identified areas for future research and scholarship to promote ethical conduct of HIV phylogenetic research.
Impact of Housing and Infrastructure on handwashing in Peru
Authors: Malika Nipher M , Barbagelatta Guisella , Penny Mary , Reynolds Kelly A , Sinclair Ryan
Published: March 2020

Background

The metropolitan area of Lima, Peru has a third of the nation’s population living in slum dwellings that are hypothesized to contribute to inefficient household hygienic practices. The purpose of this study was to quantitatively assess which living conditions have the greatest impact on handwashing practices.

Methods

A cross-sectional epidemiological design of participants ≥16 y of age from San Juan de Miraflores, a slum on the outskirts of Lima, Peru, was used. Poisson regression was applied to assess the impact of living conditions on handwashing practices.

Results

We could not demonstrate a relationship between living conditions (home structure, overcrowding, water, grey water disposal) and reported handwashing. The reported lack of handwashing is associated with the number of children in the home (those with children <5 y of age were more likely not to report washing their hands) and length of stay in the slum in years.

Conclusions

Living conditions play an important role in one’s health, therefore improved study designs are needed to determine which strategies are likely to be the most effective in improving outcomes for slum dwellers.
Effects of BMP7 produced by group 2 innate lymphoid cells on adipogenesis
Authors: Miyajima Yurina , Ealey Kafi N , Motomura Yasutaka , Mochizuki Miho , Takeno Natsuki , Yanagita Motoko , Economides Aris N , Nakayama Manabu , Koseki Haruhiko , Moro Kazuyo
Published: March 2020

Group 2 innate lymphoid cells (ILC2s) are type 2 cytokine-producing cells that have important roles in helminth infection and allergic inflammation. ILC2s are tissue-resident cells, and their phenotypes and roles are regulated by tissue-specific environmental factors. While the role of ILC2s in the lung, intestine and bone marrow has been elucidated in many studies, their role in adipose tissues is still unclear. Here, we report on the role of ILC2-derived bone morphogenetic protein 7 (BMP7) in adipocyte differentiation and lipid accumulation. Co-culture of fat-derived ILC2s with pluripotent mesenchymal C3H10T1/2 cells and committed white preadipocyte 3T3-L1 cells resulted in their differentiation to adipocytes and induced lipid accumulation. Co-culture experiments using BMP7-deficient ILC2s revealed that BMP7, produced by ILC2s, induces differentiation into brown adipocytes. Our results demonstrate that BMP7, produced by ILC2s, affects adipocyte differentiation, particularly in brown adipocytes.
What Ibero-American hospitals do when things go wrong? A cross-sectional international study
Authors: Mira José Joaquín , Carrillo Irene , García-Elorrio Ezequiel , Andrade-Lourenção Daniela Campos D E , Pavan-Baptista Patricia Campos , Franco-Herrera Astolfo León , Campos-Castolo Esther Mahuina , Poblete Rodrigo , Limo Juan , Siu Hugo , Sousa Paulo
Published: March 2020

Objective

To know what hospital managers and safety leaders in Ibero-American countries are doing to respond effectively to the occurrence of adverse events (AEs) with serious consequences for patients.

Design

Cross-sectional international study.

Setting

Public and private hospitals in Ibero-American countries (Argentina, Brazil, Chile, Colombia, Mexico, Peru, Portugal and Spain).

Participants

A convenience sample of hospital managers and safety leaders from eight Ibero-American countries. A minimum of 25 managers/leaders from each country were surveyed.

Interventions

A selection of 37 actions for the effective management of AEs was explored. These were related to the safety culture, existence of a crisis plan, communication and transparency processes with the patients and their families, attention to second victims and institutional communication.

Main Outcome Measure

Degree of implementation of the actions studied.

Results

A total of 190 managers/leaders from 126 (66.3%) public hospitals and 64 (33.7%) private hospitals participated. Reporting systems, in-depth analysis of incidents and non-punitive approaches were the most implemented interventions, while patient information and care for second victims after an AE were the least frequent interventions.

Conclusions

The majority of these hospitals have not protocolized how to act after an AE. For this reason, it is urgent to develop and apply a strategic action plan to respond to this imperative safety challenge. This is the first study to identify areas of work and future research questions in Ibero-American countries.
Bacterial population kinetics in heteroresistant Mycobacterium tuberculosis harbouring rare resistance-conferring mutations in gyrA and rpoB imply an epistatic interaction of mutations in a pre-XDR-TB patient
Authors: Yoshida Shiomi , Iwamoto Tomotada , Arikawa Kentaro , Sekizuka Tsuyoshi , Kuroda Makoto , Inoue Yoshikazu , Mitarai Satoshi , Tsuji Taisuke , Tsuyuguchi Kazunari , Suzuki Katsuhiro
Published: March 2020

Objectives

Bacterial population kinetics of strains harbouring drug resistance-conferring mutations within a patient often show cryptic resistance in clinical practice. We report a case that showed emergence and dominance of Mycobacterium tuberculosis with uncommon rpoB and gyrA mutations, followed by an rpoC compensatory mutation, during treatment.

Methods

A pre-XDR-TB patient showed heteroresistance to rifampicin and levofloxacin during treatment as a result of intermittent self-cessation. WGS was applied to investigate intra-host strain composition using five pairs of isolates from sputum samples.

Results

The subclone in this study possessed rare mutations conferring resistance to rifampicin (rpoB V170F) and levofloxacin (gyrA S91P) and it rapidly outcompeted other subclones during treatment that included levofloxacin but not rifampicin (<7 days). The high-probability compensatory mutation rpoC V483A also emerged and became dominant subsequent to the rpoB V170F mutation.

Conclusions

To the best of our knowledge, this is the first case showing the emergence of such a rare variant that dominated the population within a patient during treatment of TB.