bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Plasmodium vivax malaria and antimalarial treatment on cytochrome P450 activity in Brazilian patients
Authors: Almeida Anne Cristine , Elias Anna Beatriz Ribeiro , Marques Maria Paula , de Melo Gisely Cardoso , da Costa Allyson Guimarães , Figueiredo Erick Frota Gomes , Brasil Larissa Wanderley , Rodrigues‐Soares Fernanda , Monteiro Wuelton Marcelo , de Lacerda Marcus Vinicius Guimarães , Lanchote Vera Lucia , Suarez‐Kurtz Guilherme
Published: September 2020

Aims

To investigate the impact of Plasmodium vivax malaria and chloroquine‐primaquine chemotherapy on CYP2D6 and CYP2C19 activity in patients from the Brazilian Amazon.

Methods

Adult patients (n = 30) were given subtherapeutic doses of CYP2D6 and CYP2C19 phenotypic probes metoprolol (10 mg) and omeprazole (2 mg) in three different stages of vivax malaria illness: acute disease (study phase 1), post chemotherapy (phase 2) and convalescence (stage 3). Plasma concentrations of probes and CYP‐hydroxylated metabolites (α‐OH metoprolol and 5‐OH omeprazole) were measured using LC/MS/MS. Two pharmacokinetic metrics were used to estimate CYP activity: (a) ratio of plasma concentrations of probe/metabolite at 240 minutes after administration of the probes and (b) ratio of areas under the time‐concentration curves for probe/metabolite (AUC0‐12h). For statistical analysis, the pharmacokinetic metrics were normalized to the respective values in phase 3. Taqman assays were used for CYP2D6 and CYP2C19 genotyping. Cytokines levels were measured using cytometric bead array.

Results

Both pharmacokinetic metrics for metoprolol and omeprazole, and plasma concentrations of cytokines IL‐6, IL‐8 and IL‐10 varied significantly across the three study phases (ANOVA P < 0.0001). Post hoc tests showed greater metoprolol:α‐OH metoprolol ratios in phases 1 and 2 compared to phase 3, larger omeprazole:5‐OH omeprazole ratios in phase 1 than in phases 2 and 3, and higher circulating IL‐6, IL‐8 and IL‐10 in phase 1 than in phases 2 and 3.

Conclusion

P. vivax malaria and treatment altered CYP2D6 and CYP2C19 metabolic phenotypes. CYP2C19 inhibition is attributed to a higher level of circulating proinflammatory cytokines, while suppression of CYP2D6 is ascribed mainly to chloroquine exposure.
Clinical evaluation of drug–drug interactions between the cytochrome P450 substrates selexipag and clopidogrel in Japanese volunteers
Authors: Katayama Naoki , Odagiri Keiichi , Hakamata Akio , Kamiya Chiaki , Uchida Shinya , Tanaka Shimako , Inui Naoki , Namiki Noriyuki , Tatsumi Koichiro , Watanabe Hiroshi
Published: September 2020

Aims

The strong cytochrome P450 (CYP) 2C8 inhibitor gemfibrozil has been demonstrated to increase the area under the plasma concentration–time curve from 0 to infinity (AUC0–∞) of ACT‐333679, an active metabolite of selexipag, by 11‐fold. Similarly to gemfibrozil, the CYP2C8 inhibitor clopidogrel increased ACT‐333679 concentration by 1.9‐fold after a single loading dose (300 mg once daily) and 2.7‐fold after repeated treatment with the maintenance dose (75 mg once daily) in Europeans. However, the effects of clopidogrel on the pharmacokinetics of selexipag and ACT‐333679 have not been fully elucidated in the Japanese population.

Methods

We investigated the effect of clopidogrel on the pharmacokinetics of selexipag and ACT‐333679 in 14 healthy Japanese volunteers.

Results

The concomitant administration of clopidogrel with selexipag did not influence the maximum concentration and AUC0‐∞ of selexipag, whereas it significantly increased AUC0‐∞ of ACT‐333679 by approximately 1.90‐fold (90% confidence interval 1.69–2.14) without changing the maximum concentration. When selexipag was administered 1 day after clopidogrel was discontinued, the increase in AUC0‐∞ of ACT‐333679 was 1.37‐fold (90% confidence interval 0.93–2.02), suggesting that, although the inhibitory effect of clopidogrel on CYP2C8 was reduced, it persisted for at least 1 day after withdrawal.

Conclusion

Our results demonstrated the impact of clopidogrel on the pharmacokinetics of selexipag and its active metabolite and suggested that selexipag should be carefully prescribed with clopidogrel with dose adjustment or reducing the dosing frequency in Japanese clinical settings.
Staying Alive: 1970s Southern Cone Exiles in the UK
Authors: Miorelli Romina , Piersanti Valentina
Published: September 2020

This article seeks to contribute to the study of the 1970s dictatorships in Argentina, Chile and Uruguay by looking at one specific aspect of those regimes: exile. It considers exile in the UK, a host country on which research is limited, and claims that the fundamental political ideas that had inspired these exiles did not vanish but were variously reshaped, depending on changing political circumstances, how the exiles interacted with local forms of solidarity, and how they lived through the personal challenges that they experienced during exile.
Suitable test concentration of cobalt and concomitant reactivity to nickel and chromium: A multicentre study from the Swedish Contact Dermatitis Research Group
Authors: Isaksson Marléne , Hagvall Lina , Glas Bo , Lagrelius Maria , Lidén Carola , Matura Mihaly , Nyman Gunnar , Stenberg Berndt , Svedman Cecilia , Bruze Magnus
Published: September 2020

Background

In Sweden, cobalt chloride 0.5% has been included in the baseline series since the mid‐1980s. A recent study from Stockholm showed that cobalt chloride 1% petrolatum (pet.) was more suitable than 0.5%. Cobalt chloride at 1.0% has been patch tested for decades in many European countries and around the world.

Objectives

To study the suitability of patch testing to cobalt 1.0% vs 0.5% and to analyze the co‐occurrence of allergy to cobalt, chromium, and nickel.

Results

Contact allergy to cobalt was shown in 90 patients (6.6%). Eighty (5.9%) patients tested positive to cobalt 1.0%. Thirty‐seven of the 90 patients (41.1%) with cobalt allergy were missed by cobalt 0.5% and 10 (0.7%) were missed by cobalt 1.0% (P < .001). No case of patch test sensitization was reported. Allergy to chromium was seen in 2.6% and allergy to nickel in 13.3%. Solitary allergy to cobalt without nickel allergy was shown in 61.1% of cobalt‐positive individuals. Female patients had larger proportions of positive reactions to cobalt (P = .036) and nickel (P < .001) than males.

Conclusion

The results speak in favor of replacing cobalt chloride 0.5% with cobalt chloride 1.0% pet. in the Swedish baseline series, which will be done 2021.
A novel feature‐based network with sequential information for textile defect detection
Authors: Li Chenxi , Liu Tao , Ye Wei
Published: September 2020

In this paper, a novel feature‐based attention network with sequential information is proposed for fabric defect detection. As an important part of the textiles industry, fabric quality inspection needs to be automated in the latest wave of intelligent transformation. To this end, fabric defect detection algorithms have been widely studied. In this paper, an efficient defect detection model for fabrics was built. As the appearances of defects change with the type of fabric, manual features which denote the overall situation of the fabric are used as prior knowledge. The feature‐based attention module discussed in this paper can generate attention maps from these manual features to rectify the responses of the feature maps according to the whole situation of the input image. Multidirectional long short‐term memory networks are implemented to extract context information from continuous defects. When making a judgement, taking sequential information into consideration may reduce the number of unexpected misjudged decisions compared with the number of those made independently pixel by pixel. Both of those two modules can be integrated into any existing convolutional neural network model and trained in an end‐to‐end manner. A fabric defect dataset is built to train and test the models. In this paper, several models with different architectures are implemented to verify our ideas, and are supported by results confirming the efficiency of the proposed methods.
Persistent Privilege? Institutional Education Gaps during Vietnam's Economic Boom
Authors: Phan Diep , Coxhead Ian
Published: September 2020

A persistent public–private sector difference in returns to skills is one sign that Vietnam's transition from command to market economy remains incomplete. Matching this is a large gap in post‐compulsory education enrollments, favoring children from families with members employed by government or state enterprises. We compare that gap between 2004 and 2014, a decade during which Vietnam experienced a boom in private‐sector and foreign‐invested economic activity. Despite the boom, we find a persistent and widening enrollment gap between “state” and “non‐state” households, which are similar in other observable respects. This institutional gap is not the only basis for enrollment differences—the ethnicity gap has also widened, even as rural–urban disparities have diminished—but they may contribute to slow and unequal progress in overall educational attainment. Unless addressed, enrollment gaps are likely to worsen intergenerational inequality and may reduce long‐run economic growth.
Motor imagery in children with unilateral cerebral palsy: a case–control study
Authors: Souto Deisiane O , Cruz Thalita K F , Fontes Patrícia L B , Haase Vitor G
Published: September 2020

Aim

To evaluate whether children with cerebral palsy (CP) are able to engage in a motor imagery task. Possible associations between motor imagery and functional performance, working memory, age, and intelligence were also investigated.

Method

This is a case–control study that assessed 57 children (25 females, 32 males) with unilateral CP, aged 6 to 14 years (mean age: 10y 4mo; SD 2y 8mo) and 175 typically developing (control) children, aged 6 to 13 years (87 females, 88 males; mean age: 9y 4mo; SD 1y 11mo). The hand laterality judgment task was used to measure motor imagery ability. Reaction time, accuracy, and the effect of the biomechanical constraints were assessed in this task.

Results

Performance in both groups followed the biomechanical constraints of the task, that is, longer reaction times to recognize stimuli rotated laterally when compared to medial stimuli. Reaction time means did not differ significantly between groups (p>0.05). Significant differences between the unilateral CP and control groups were observed for accuracy (p<0.05). Functional performance and working memory were correlates of motor imagery tasks.

Interpretation

Results suggest that children with unilateral CP can engage in motor imagery; however, they commit more errors than typically developing controls. In addition, their performance in tasks of motor imagery is influenced by functional performance and working memory.
Cognitive performance in midlife type 2 diabetes: results from the ENBIND study
Authors: Dyer A. H. , McKenna L. , Gamage G. , Bourke N. M. , Killane I. , Widdowson M. , Woods C. P. , Gibney J. , Reilly R. , O’Neill D. , Kennelly S. P.
Published: September 2020

Aims

To establish the impact of uncomplicated type 2 diabetes on cognitive and neuropsychological performance in midlife.

Methods

We performed a cross‐sectional study of middle‐aged adults with uncomplicated type 2 diabetes and a cohort of healthy control participants. General cognition was assessed using the Montreal Cognitive Assessment test and neuropsychological assessment was undertaken using a detailed neuropsychological assessment battery.

Results

A total of 152 participants (102 with type 2 diabetes and 50 controls) were recruited (mean age 52 ± 8 years, 51% women). Participants with midlife type 2 diabetes were more than twice as likely to make an error on the Montreal Cognitive Assessment test [incidence rate ratio 2.44 (95% CI 1.54 to 3.87); P < 0.001]. Further, type 2 diabetes was also associated with significantly lower memory composite score [β: −0.20 (95% CI −0.39 to −0.01); P = 0.04] and paired associates learning score [β: = −1.97 (95% CI −3.51, −0.43); P = 0.01] on the neuropsychological assessment battery following adjustment for age, sex, BMI, educational attainment and hypercholesterolaemia.

Conclusions

Even in midlife, type 2 diabetes was associated with small but statistically significant cognitive decrements. These statistically significant decrements, whilst not clinically significant in terms of objective cognitive impairment, may have important implications in selecting out individuals most at risk of later cognitive decline for potential preventative interventions in midlife.
Vitamin D receptor gene polymorphisms are associated with psoriasis susceptibility and the clinical response to calcipotriol in psoriatic patients
Authors: Liu Junlin , Wang Wei , Liu Kun , Wan Duoyan , Wu Zhiming , Cao Zhirui , Luo Yang , Xiao Chuanliu , Yin Mei
Published: September 2020

Psoriasis is a common genetic disease characterized by hyperproliferation and disordered maturation of keratinocytes. To date, many association studies between psoriasis and VDR gene have been conducted, but the results are controversial. Furthermore, vitamin D3 analogue has anti‐psoriatic activity; however, the clinical response is variable. This study was conducted to explore whether VDR gene polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients. A total of 110 patients and 183 controls were genotyped for VDR gene polymorphisms rs2228570, rs731236, rs1544410 and rs7975232 by LDR method. SNP‐based and haplotype‐based association analyses were subsequently performed. Patients with PASI < 3 were treated with calcipotriol ointment monotherapy. After 6 weeks of therapy, the correlations between efficacy and the genotypes of each polymorphism were evaluated. The results showed that for rs7975232, allele A was significantly over‐represented in psoriasis patients relative to controls (39.09% vs. 27.05%, OR (95% CI) = 1.731 (1.213‐2.471)), and compared with the reference CC genotype, the following ORs were observed: AA genotype OR = 2.404 (95% CI: 1.085‐5.328; P = .034) and GA genotype OR = 2.143 (95% CI: 1.283‐3.579; P = .005). Haplotype analyses showed that the rs2228570/rs731236/rs1544410/rs7975232 CTGA was significantly over‐represented in psoriasis patients compared with controls (OR (95% CI)=1.907 (1.132‐3.214); P = .020). Among the patients with PASI < 3, the response rates to calcipotriol were significantly higher in patients with rs7975232 CC genotypes than in those with other genotypes (x2 = 9.172, P = .010). These data suggest that VDR polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients.
Activated melanoma vessels: A sticky point for successful immunotherapy
Authors: Weishaupt Carsten , Goerge Tobias , Loser Karin
Published: September 2020

Metastatic melanoma is a devastating disease with a marginal—albeit increasing—hope for cure. Melanoma has a high mutation rate which correlates to the expression of numerous neo‐antigens and thus is associated with the potential to induce and strengthen effective antitumoral immunity. However, the incomplete and potentially insufficient response to established immunotherapies (response rates usually do not markedly exceed 60%) already points to the need of further studies to improve treatment strategies. Multiple tumor escape mechanisms that allow melanoma to evade from antitumoral immune responses have been characterized and must be overcome to achieve a better clinical efficacy of immunotherapies. Recently, promising progress has been made in targeting tumor vasculature to control and increase the infiltration of tumors with effector lymphocytes. It has been hypothesized that amplified lymphocytic infiltrates in melanoma metastases result in a switch of the tumor microenvironment from a non‐inflammatory to an inflammatory state. In this view point essay, we discuss the requirements for successful homing of lymphocytes to melanoma tissue and we present a mouse melanoma xenograft model that allows the investigation of human tumor vessels in vivo. Furthermore, current clinical studies dealing with the activation of melanoma vasculature for enhanced effectiveness of immunotherapy protocols are presented and open questions for routine clinical application are addressed.
The development and validation of the Privacy and Data Security Concerns Scale (PDSCS)
Authors: Brady Grant M. , Truxillo Donald M. , Bauer Talya N. , Jones Mark P.
Published: September 2020

This study describes the development and validation of the Privacy and Data Security Concerns Scale (PDSCS), designed to assess job applicants’ privacy and data security concerns. Validity evidence for the PDSCS was established with four steps including: item generation and content validation, item reduction, confirmatory factor analysis, and construct and criterion validity. Our findings supported the content and proposed factor structure of the nine‐item PDSCS. Specifically, the proposed three‐factor structure (with the subdimensions: Secure connection, inappropriate use of information, and mistrust in employer security practices) as well as a second‐order factor, (termed privacy and data security concerns) were confirmed. Additionally, evidence is presented for the criterion validity of the PDSCS and its subdimensions.
Re‐connecting capitalism: prospects for the regulatory reform of the employee interest in UK takeovers
Authors: Rees Chris , Gold Michael
Published: September 2020

This article draws upon the disconnected capitalism thesis (DCT) to analyse UK takeovers and their implications for workers. The DCT refers to the disconnect between the source of value creation (the labour process) and the wider political economy. Specifically, we highlight a particular aspect of this disconnect whereby those who create value and have a long‐term stake in firms (employees and managers at the firm level) are disconnected from decisions regarding takeovers, as a consequence of wider economic and political trends (processes of financialisation/marketisation and associated state support for a neoliberal takeover regime). We outline these trends and argue the case for a re‐connect, which will require empowering employees and managers to have more influence in takeover decisions and, in turn, disempowering shareholders and financial intermediaries. The article thus highlights the regulatory space for takeovers and considers feasible policy options, a set of interlinked regulatory changes, which will in particular require a more assertive state.
Innovative postnatal risk assessment in preventive child health Care: A study protocol
Authors: van Minde Minke R. C. , Remmerswaal Marianne , Raat Hein , Steegers Eric A. P. , de Kroon Marlou L. A.
Published: September 2020

Aim

To introduce the rationale and design of a postnatal risk assessment study, which will be embedded in Preventive Child Health Care. This study will evaluate: (a) the predictive value of an innovative postnatal risk assessment, meant to assess the risk of growth and developmental problems in young children; and (b) its effectiveness in combination with tailored care pathways.

Design

This study concerns a historically controlled study design and is designed as part of the Healthy Pregnancy 4 All‐2 program. We hypothesize that child growth and developmental problems will be reduced in the intervention cohort due to the postnatal risk assessment and corresponding care pathways.

Methods

The study was approved in August 2016. Children and their parents, visiting well‐baby clinics during regular visits, will participate in the intervention (N = 2,650). Additional data of a historical control group (N = 2,650) in the same neighbourhoods will be collected. The intervention, consisting of the risk assessment and its corresponding care pathways, will be executed in the period between birth and 2 months of (corrected) age. The predictive value of the risk assessment and its effectiveness in combination with its corresponding care pathways will be assessed by Preventive Child Health Care nurses and physicians in four Preventive Child Health Care organisations in three municipalities with adverse perinatal outcomes. A total risk score above a predefined threshold, which is based on a weighted risk score, determines structured multidisciplinary consultation.

Discussion

The successful implementation of this innovative postnatal risk assessment including corresponding care pathways has potential for further integration of risk assessment and a family‐centred approach in the work process of Preventive Child Health Care nurses and physicians.

Impact

This study introduces a systematic approach in postnatal health care which may improve growth and developmental outcomes of children and even future generations.
Trade‐offs between ontogenetic changes and food consumption in Brazilian silverside Atherinella brasiliensis from two tropical estuaries
Authors: Júnior Alexandre da Gama Fernandes Vieira , de Lima Diele Emele Pontes Carvalho , dos Santos Sales Natalice , de Freitas Terra Bianca , Pessanha André
Published: September 2020

Salinity variation in estuarine environments influences the distribution of fish species as well as the availability of food resources to be used by them. This study examines the effect of the range of salinity on the trade‐off between growth and feeding intensity of Atherinella brasiliensis from two tropical estuaries (positive and hypersaline). To investigate the effects of salinity, we hypothesized that hypersalinity negatively affects foraging intensity, consumption and prey selection by the Brazilian silverside, leading to differences in body condition. Sampling was carried out using the beach seine method in two areas of the estuaries (upper and lower zone) during rainy and dry periods. A total of 2549 stomachs (1124 for the positive estuary and 1425 for the hypersaline estuary) were examined, and the results indicated a dissimilarity of 92.7% of the diet between environments. In the positive estuary, there was more predation on Calanoida, Gastropoda, Hymenoptera, Ceratopogonidae larvae and Decapoda larvae, while Alga and plant‐material characterized the diet in the hypersaline estuary. Significant correlations between the volume of food and salinity were observed in both estuaries. The vacuity index indicated that hypersaline environments presented higher contributions of semifull stomachs, indicating an intense consumption of algae. On the other hand,in the positive estuary, these values were less intense, but the stomachs were always with animal items. The variation found for both environments reinforces the effect of salinity on the physiological mechanism of the populations once the higher proportions of filled stomachs in the hypersaline environment indicate the need for constant and high ingestion of prey to guarantee the pronounced energy expenditure with osmoregulation.
Deaths during pregnancy, childbirth and puerperium: Exploring causes, context and evidence from Eastern India
Authors: Sk Md Illias Kanchan , Paswan Balram , Anand Ankit , Chowdhury Poulomi , Naskar Tapan Kumar
Published: September 2020

Aim

The study was aimed to identify the specific reasons and circumstances of maternal deaths in West Bengal.

Methods

The present study is a retrospective study of 317 maternal deaths, conducted between November 2013 and October 2015 at two major referral hospitals of eastern India, West Bengal. The frequencies, proportions, measures of central tendency and dispersion were used to describe the data. The data were analyzed using the statistical software spss version 20.0. ArcGIS 10.1 was also employed to show the distributional pattern of maternal deaths.

Results

The overall maternal mortality ratio was estimated as 561 per 100 000 live births. Eclampsia or hypertensive disorders of pregnancy contributed to one‐third (33.1%, n = 105/317) of maternal deaths. The maternal deaths were more common (41%) among women belonging to the age group of 20–24 years and primiparous (36.9%) group. The average distance for traveling to reach the final hospital was 47.37 km. Approximately, three‐fourths (72.2%) of maternal deaths were in the post‐partum period. Half of the women (50.5%) sought medical care after 12 hrs of developing complications. The majority of the cases (80.1%) were referred and about 45% of patients had a cesarean section.

Conclusion

The result suggests there was a shift in causes of maternal deaths from hemorrhage to eclampsia. Establishment of separate eclampsia units at lower‐level health facilities may be a more plausible pathway to prevent eclampsia‐related maternal deaths in West Bengal.
Maternal perceptions of sleep problems among children and mothers during the coronavirus disease 2019 (COVID‐19) pandemic in Israel
Authors: Zreik Ghadir , Asraf Kfir , Haimov Iris , Tikotzky Liat
Published: September 2020

Despite the marked impact of the coronavirus disease 2019 (COVID‐19) pandemic on the life of families and its possible negative implications for sleep, little is known about how sleep among parents and children has been impacted by this current crisis. In the present study, we addressed, for the first time, possible consequences of the COVID‐19 crisis and home confinement on maternal anxiety, maternal insomnia, and maternal reports of sleep problems among children aged 6–72 months in Israel (N = 264). Our results revealed a high frequency of maternal clinical insomnia during the COVID‐19 pandemic: 23% during the pandemic, compared to only 11% before the pandemic (retrospective reports about 1–2 months before the pandemic). About 80% of mothers reported mild‐to‐high levels of current COVID‐19 anxiety. The majority of mothers reported no change in their child’s sleep quality, duration, and sleeping arrangement. However, about 30% reported a negative change in child’s sleep quality and a decrease in sleep duration, and there were also mothers who reported a positive change. These findings suggest that the changes in sleep patterns during the COVID‐19 pandemic are varied and that no unified change for the worse should be expected. Further consideration of changes in sleep within the family context during this ongoing crisis is needed.
Long‐term follow‐up of diabetic and non‐diabetic patients with chronic hepatitis C successfully treated with direct‐acting antiviral agents
Authors: Ciancio Alessia , Ribaldone Davide G. , Dotta Anna , Giordanino Chiara , Sacco Marco , Fagoonee Sharmila , Pellicano Rinaldo , Saracco Giorgio M.
Published: September 2020

Background and aims

Clearance of hepatitis C virus (HCV) is associated with improved glycometabolic control in patients with diabetes mellitus (DM) but whether this effect is maintained over the long term with a reduction in liver‐related events (LRE) is still debated. To address these issues, we conducted a long‐term prospective study on diabetic and non‐diabetic patients with chronic hepatitis C cured by direct antiviral agents (DAAs).

Methods

Among 893 recruited patients, 15.7% were diabetic (Group 1) and 84.3% non‐diabetic (Group 2); changes in fasting glucose (FG) and glycated haemoglobin (HbA1c) levels were assessed in Group 1 while the incidence of LRE was established in the whole cohort. Differences between groups were evaluated and independent predictors of unfavourable clinical outcome were established.

Results

After a mean follow up of 44.5 months, a significant reduction in FG and HbA1c values was found in Group 1. Death was reported in 5.7% of patients in Group 1 vs 1.6% in Group 2 (P = .003), hepatocellular carcinoma (HCC)‐free survival was significantly lower in Group 2 (P = .015) as well as LRE‐free survival in Group 1 cirrhotic patients (P = .0006). After adjustment for baseline variables, cirrhosis and albumin levels emerged as independent predictors of LRE; low albumin levels, DM and central obesity were associated with HCC risk in cirrhotic patients while insulin therapy emerged as unfavourable predictor among diabetics.

Conclusions

SVR achieved by DAAs is associated with long‐term improvement of glycometabolic control in diabetic patients, but among cirrhotics DM still exerts a detrimental effect on the liver.
The myth of ivory tower versus practice‐oriented research: A systematic review of randomised studies in medical education
Authors: Tolsgaard Martin G. , Mahan Kulasegaram Kulamakan , Woods Nicole N. , Brydges Ryan , Ringsted Charlotte , Dyre Liv
Published: September 2020

Context

A long‐standing myth in medical education research is a divide between two different poles: research aiming to advance theory with little focus on practical applications (‘ivory tower’ research) and practically oriented research aiming to serve educators and decision‐makers with little focus on advancing theory (‘in‐the‐trenches’ practice). We explored this myth in a sample of randomised medical education studies using Stokes’ four‐quadrant framework for the classification of research perspective.

Methods

We searched MEDLINE, Embase, CINAHL, PsychINFO, ERIC, Web of Science and Scopus for studies in medical education using a randomised design that were published between 1 January 2018 and 31 December 2018. We used Stokes’ four‐quadrant framework to categorise the studies according to their use of theory, concepts and their justification for practical use. We compared medical education research published in medical education journals and clinical journals.

Results

A total of 150 randomised studies were included in the analysis. The largest segment of studies (46.7%) was categorised as use‐inspired basic research (Pasteur's Quadrant), closely followed by pure applied research (40.7%, Edison's Quadrant). Only a few studies were categorised as aiming to advance knowledge with no thought for practical educational application (2.0%, Bohr's Quadrant).

The proportion of studies that included educational concepts and theory differed according to publication in clinical journals or medical education journals: 40.5% vs 71.8%, respectively, P < .001. There were no differences between journals with regard to the proportion of studies that included a practical educational or clinical rationale (P = .99).

Conclusion

In a large sample of studies using randomised designs, we found no evidence to support the myth that medical education research divides between two singular poles represented by ‘ivory tower research’ and ‘in‐the‐trenches practice’. We did confirm prevailing assumptions regarding an emphasis on non‐theoretical medical education research in clinical journals.
Nonredundant functions of Mycobacterium tuberculosis chaperones promote survival under stress
Authors: Harnagel Alexa , Lopez Quezada Landys , Park Sae Woong , Baranowski Catherine , Kieser Karen , Jiang Xiuju , Roberts Julia , Vaubourgeix Julien , Yang Amy , Nelson Brock , Fay Allison , Rubin Eric , Ehrt Sabine , Nathan Carl , Lupoli Tania J.
Published: September 2020

Bacterial chaperones ClpB and DnaK, homologs of the respective eukaryotic heat shock proteins Hsp104 and Hsp70, are essential in the reactivation of toxic protein aggregates that occur during translation or periods of stress. In the pathogen Mycobacterium tuberculosis (Mtb), the protective effect of chaperones extends to survival in the presence of host stresses, such as protein‐damaging oxidants. However, we lack a full understanding of the interplay of Hsps and other stress response genes in mycobacteria. Here, we employ genome‐wide transposon mutagenesis to identify the genes that support clpB function in Mtb. In addition to validating the role of ClpB in Mtb's response to oxidants, we show that HtpG, a homolog of Hsp90, plays a distinct role from ClpB in the proteotoxic stress response. While loss of neither clpB nor htpG is lethal to the cell, loss of both through genetic depletion or small molecule inhibition impairs recovery after exposure to host‐like stresses, especially reactive nitrogen species. Moreover, defects in cells lacking clpB can be complemented by overexpression of other chaperones, demonstrating that Mtb's stress response network depends upon finely tuned chaperone expression levels. These results suggest that inhibition of multiple chaperones could work in concert with host immunity to disable Mtb.
Rare/cryptic Aspergillus species infections and importance of antifungal susceptibility testing
Authors: Tsang Chi‐Ching , Tang James Y. M. , Ye Haiyan , Xing Fanfan , Lo Simon K. F. , Xiao Chenlu , Han Lizhong , Wu Alan K. L. , Ngan Antonio H. Y. , Law Kwok‐Cheung , To Ying‐Nam , Sze Dorothy T. T. , Chim Oscar H. Y. , Hui Teresa W. S. , Leung Carl W. H. , Zhu Tianrenzheng , Yao Chunyan , Tse Brian P. H. , Lau Susanna K. P. , Woo Patrick C. Y.
Published: September 2020

Background

The number of patients infected with Aspergillus rose dramatically in recent years. However, studies on the clinical spectrum and antifungal susceptibilities of non‐classical (non‐fumigatus, non‐flavus, non‐niger and non‐terreus) pathogenic Aspergillus species are very limited.

Objectives

We examined the clinical spectrum and antifungal susceptibilities of 34 non‐duplicated, non‐classical Aspergillus isolates collected from Hong Kong, Shenzhen and Shanghai.

Methods

The Aspergillus isolates were identified by internal transcribed spacer, partial BenA and partial CaM sequencing and phylogenetic analyses. Susceptibility testing against eight antifungals was performed following the European Committee for Antimicrobial Susceptibility Testing's methodology.

Results

The 34 Aspergillus isolates were identified as 14 different rare/cryptic species of four sections (Flavi [n = 8], Nidulantes [n = 8], Nigri [n = 17] and Restricti [n = 1]). Except for one patient whose clinical history could not be retrieved, 72.7% of the remaining patients had underlying conditions predisposing them to Aspergillus infections. The most common diseases were pulmonary infections (n = 15), followed by skin/nail infections (n = 6), chronic otitis externa and/or media (n = 5), wound infections (n = 2) and mastoiditis/radionecrosis (n = 1), while three were colonisations. Five patients succumbed due to the infections during the admission, and another two died 5 years later because of chronic pulmonary aspergillosis. Antifungal susceptibility testing showed that they possessed different susceptibility profiles compared to the classical Aspergillus species. The majority of isolates characterised were sensitive or wild‐type to amphotericin B. The minimum effective concentrations for all the three echinocandins were also low.

Conclusion

Susceptibility testing should be performed for infections due to these rare/cryptic Aspergillus species to guide proper patient management.
Studies on Schismatoglottideae (Araceae) of Peninsular Malaysia II: Schismatoglottis guabatuensis [Calyptrata clade], a new locally endemic limestone‐obligated species
Authors: Yeng Wong Sin , Boyce Peter C.
Published: September 2020

Schismatoglottis guabatuensis is described and illustrated as a new species of the Calyptrata clade restricted to the limestone of Batu Caves, Selangor, Malaysia. It is compared with the three other described species of the Calyptrata clade present in Peninsula Malaysia.
The role of protein kinase D (PKD) in intracellular nutrient sensing and regulation of adaptive responses to the obese environment
Authors: Renton Mark C. , McGee Sean L. , Howlett Kirsten F.
Published: September 2020

Obesity is associated with ectopic accumulation of lipids, which is implicated in the development of insulin resistance, type 2 diabetes mellitus and cardiovascular disease. As the global prevalence of obesity continues to rise, it is becoming increasingly important to understand the underlying cellular mechanisms of this disease. Protein kinase D (PKD) is an intracellular signalling kinase with well characterized roles in intracellular vesicle transport and secretion, cancer cell proliferation and cardiac hypertrophy. However, emerging evidence also highlights PKD as a novel nutrient sensor. PKD activation is mediated by the accumulation of the lipid intermediate diacylglycerol, and PKD activity in the liver, heart and adipose tissue increases upon feeding. In obesity, PKD signalling is linked to reduced insulin signalling and dysfunction in adipose tissue, liver and heart, whilst in the pancreas, PKD is essential for the compensatory increase in glucose‐stimulated insulin secretion from β‐cells during obesity. Collectively, these studies reveal aspects of PKD signalling that are involved in the tissue‐specific responses to obesity. This review summarizes the emerging evidence suggesting that PKD plays an important role in regulating the adaptive response to the obese environment.
Metabolomic differences of exhaled breath condensate among children with and without asthma
Authors: Chang‐Chien Ju , Huang Hsin‐Yi , Tsai Hui‐Ju , Lo Chi‐Jen , Lin Wan‐Chen , Tseng Yu‐Lun , Wang Shih‐Ling , Ho Hung‐Yao , Cheng Mei‐Ling , Yao Tsung‐Chieh
Published: September 2020

Background

There remains an unmet need in objective tests for diagnosing asthma in children. The objective of this study was to investigate the potential of metabolomic profiles of exhaled breath condensate (EBC) to discriminate stable asthma in Asian children in the community.

Methods

One hundred and sixty‐five Asian children (92 stable asthma and 73 non‐asthmatic controls) participating in a population‐based cohort were enrolled and divided into training and validation sets. Nuclear magnetic resonance‐based metabolomic profiles of EBC samples were analyzed by using orthogonal partial least squares discriminant analysis.

Results

EBC metabolomic signature (lactate, formate, butyrate, and isobutyrate) had an area under the receiver operator characteristic curve (AUC) of 0.826 in discriminating children with and without asthma in the training set, which significantly outperformed FeNO (AUC = 0.574; P < .001) and FEV1/FVC % predicted (AUC = 0.569; P < .001). The AUC for EBC metabolomic signature was 0.745 in the validation set, which was slightly but not significantly lower than in the testing set (P = .282). We further extrapolated two potentially involved metabolic pathways, including pyruvate (P = 1.67 × 10−3; impact: 0.14) and methane (P = 1.89 × 10−3; impact: 0.15), as the most likely divergent metabolisms between children with and without asthma.

Conclusion

This study provided evidence supporting the role of EBC metabolomic signature to discriminate stable asthma in Asian children in the community, with a discriminative property outperforming conventional clinical tests such as FeNO or spirometry.
Assessment of different techniques for the administration of inhaled salbutamol in children breathing spontaneously via tracheal tubes, supraglottic airway devices, and tracheostomies
Authors: Anderson Natalie , Schultz André , Ditcham William , von Ungern‐Sternberg Britta S.
Published: September 2020

Background

Perioperative respiratory adverse events account for a third of all perioperative cardiac arrests, with bronchospasm and laryngospasm being most common. Standard treatment for bronchospasm is administration of inhaled salbutamol, via pressurized metered dose inhaler. There is little evidence on the best method of attaching the pressurized metered dose inhaler to the artificial airway during general anesthesia.

Aim

The aim of this study is to investigate the best method to deliver aerosolized salbutamol via pressurized metered dose inhaler to the lungs of an anesthetized child.

Methods

We measured salbutamol delivered by pressurized metered dose inhaler through different sized tracheal tubes, supraglottic airway devices, and tracheostomies in vitro for methods commonly employed for connecting the pressurized metered dose inhaler to the artificial airway. Breathing was simulated for patients weighing 3, 16, 50, and 75 kg. Pressurized metered dose inhaler actuation coincided with inspiration.

Results

A pressurized metered dose inhaler combined with an in‐line non‐valved or valved spacer, or the direct method, when delivered via tracheal tube, was linked with improved delivered dose of salbutamol, compared to all other methods for 3 or 50 kg simulated patients weights. The delivered dose when using a non‐valved spacer was greater than all methods for 16 and 75 kg patient weights. A spacer improved delivery for the flexible supraglottic airway device type, and there was no difference with or without a spacer for remaining types.

Conclusion

Via tracheal tube and non‐valved spacer, the following doses should be delivered after single actuation of a 100 µg labeled‐claim salbutamol dose: ~2 µg kg−1 per actuation to a 3 kg neonate, ~1 µg kg−1 per actuation to a 16 kg child, and ~ 0.5 µg kg−1 per actuation for a 50–75 kg child. The least effective methods were the syringe, and the uni‐ and bidirectional adaptor methods, which require replacement by the direct method if a spacer is unavailable.
Routine chest X‐ray following ultrasound‐guided internal jugular vein catheterization in critically ill children: A prospective observational Study
Authors: Weissbach Avichai , Gendler Yulia , Lakovsky Yaniv , Kadmon Gili , Nahum Elhanan , Kaplan Eytan
Published: September 2020

Background

Recent studies in adults have shown that routine chest X‐ray following ultrasound‐guided central venous catheter insertion through the internal jugular vein is unnecessary due to a low rate of complications.

Aims

To assess the usefulness of routine chest X‐ray following ultrasound‐guided central venous catheter insertion through the internal jugular veins in critically ill children.

Methods

A prospective observational study was conducted at a pediatric intensive care unit of a tertiary, university‐affiliated pediatric medical center. All children under the age of 18 who underwent ultrasound‐guided central venous catheter insertion through the right or left internal jugular vein between May 2018 and November 2019 were evaluated for eligibility. Procedures were prospectively documented, and chest X‐ray was screened for pneumothorax, hemothorax, central venous catheter tip position, and resultant corrective interventions.

Results

Of 105 central venous catheter insertion attempts, 99 central venous catheters (94.3%) were inserted. All were located within the venous system. None were diagnosed with pneumo/hemothorax on chest X‐ray. Twenty (20.2%; 95% CI 12.8%‐29.5%) were defined as malpositioned by strict criteria; however, only one (1%) was judged significantly misplaced by the clinical team leading to its repositioning.

Conclusions

In this critically ill pediatric cohort, all central venous catheters inserted under ultrasound guidance could have been used with safety prior to acquiring chest X‐ray. Overall chest X‐ray impacted patient management in only 1% of cases. Our results do not support delaying urgent central venous catheter use pending chest X‐ray completion in critically ill children.
Rab GTPases: Key players in melanosome biogenesis, transport, and transfer
Authors: Fukuda Mitsunori
Published: September 2020

Melanosomes are specialized intracellular organelles that produce and store melanin pigments in melanocytes, which are present in several mammalian tissues and organs, including the skin, hair, and eyes. Melanosomes form and mature stepwise (stages I–IV) in melanocytes and then are transported toward the plasma membrane along the cytoskeleton. They are subsequently transferred to neighboring keratinocytes by a largely unknown mechanism, and incorporated melanosomes are transported to the perinuclear region of the keratinocytes where they form melanin caps. Melanocytes also extend several dendrites that facilitate the efficient transfer of the melanosomes to the keratinocytes. Since the melanosome biogenesis, transport, and transfer steps require multiple membrane trafficking processes, Rab GTPases that are conserved key regulators of membrane traffic in all eukaryotes are crucial for skin and hair pigmentation. Dysfunctions of two Rab isoforms, Rab27A and Rab38, are known to cause a hypopigmentation phenotype in human type 2 Griscelli syndrome patients and in chocolate mice (related to Hermansky–Pudlak syndrome), respectively. In this review article, I review the literature on the functions of each Rab isoform and its upstream and downstream regulators in mammalian melanocytes and keratinocytes.
Jane Addams, Mohandas Gandhi, and the Promise of Soul Force
Authors: Agnew Elizabeth N.
Published: September 2020

Jane Addams (1860–1935) and Mohandas Gandhi (1869–1948) are rightly regarded as two of the 20th century’s great leaders advancing social justice and peace and through nonviolent means. Although they never met in person, they engaged similar ideas and social issues spanning nearly fifty years. In the decade and a half following World War I, they addressed one another’s work and briefly corresponded. This essay newly examines the admiration and deliberative engagement that developed between Addams and Gandhi, while highlighting their distinctive interpretations of “soul force.” I argue that each rhetorically engaged the others’ ideas and practices in ways that advanced their own approaches to nonviolent social transformation and the challenges of political consent: for Addams, moral suasion and pragmatic consensus‐building, and for Gandhi, absolute nonviolence and physical self‐suffering through acts of noncooperation and civil disobedience. This study acknowledges their shared commitment to the principle of moral goodwill toward opponents, in international and anticolonial contexts, while highlighting ways in which culture, religion, and temperament shaped their divergent nonviolent methods. Addams and Gandhi leave distinctive legacies that offer inspiration and critique for new generations addressing power and injustice.
The impact of psychiatric disorders on outcomes following heart transplantation in children
Authors: Quinlan Kia , Auerbach Scott , Bearl David W. , Dodd Debra A. , Thurm Cary W. , Hall Matt , Fuchs Dickey Catherine , Lambert Andrea Nicole , Godown Justin
Published: September 2020

Psychiatric disorders are common in pediatric HTx recipients. However, the impact of psychiatric comorbidities on patient outcomes is unknown. We aimed to assess the impact of disorders of adjustment, depression, and anxiety on HTx outcomes in children; hypothesizing that the presence of psychiatric disorders during or preceding HTx would negatively impact outcomes. All pediatric HTx recipients ≥8 years of age who survived to hospital discharge were identified from a novel linkage between the PHIS and SRTR databases (2002‐2016). Psychiatric disorders were identified using ICD codes during or preceding the HTx admission. Post‐transplant graft survival, freedom from readmission, and freedom from rejection were analyzed using the Kaplan‐Meier method. Multivariable Cox proportional hazard models were used to adjust for covariates. A total of 1192 patients were included, of which 133 (11.2%) had depression, 197 (16.5%) had anxiety, and 218 (18.3%) had adjustment disorders. The presence of depression was independently associated with higher rates of readmission (60.9% vs 54.1% at 6 months) (AHR 1.63, 95% CI 1.22‐2.18, P = .001) and inferior graft survival (70.2% vs 83.4% at 5 years) (AHR 1.62, 95% CI 1.14‐2.3, P = .007). Anxiety was independently associated with higher rates of readmission (60.4% vs 53.9% at 6 months) (AHR 1.46, 95% CI 1.09‐1.94, P = .01). Anxiety and depression in the pretransplant period are independently associated with outcomes following HTx in children. Evaluation and management of psychiatric comorbidities represents an important component of care in this vulnerable population.
Logic and Value in Wittgenstein’s Philosophy
Authors: Stiers Peter
Published: September 2020

In Tractatus Logico‐Philosophicus (TLP), Wittgenstein gave ethics the same semantic status as logic. This paper first investigates this claim from the perspective of Wittgenstein’s lifelong semantic framework. This reveals that ethical sentences are meaningless expressions, which can only be used to ostensively point out conditions of meaningfulness. Secondly, the paper assesses the implications of this conclusion for understanding the seven cryptic remarks on value and ethics in TLP. Using the connection between will and value in TLP and will and sentence interpretation in Philosophical Investigations, it is suggested that Wittgenstein held lifelong views on value and ethics.