bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of mechanical and thermal properties of polymer nanocomposites reinforced by coiled carbon nanotubes for possible application as impact absorbent
Authors: Kianfar Armin , Seyyed Fakhrabadi Mir Masoud , Mashhadi Mahmoud Mosavi
Published: November 2019

This paper presents three-dimensional finite element modeling of nanocomposite materials made from polyethylene polymer reinforced by coiled carbon nanotubes. A method of Python scripting was used to generate representative volume elements in order to determine the mechanical behavior in elastic and plastic zones as well as effective thermal conductivity using the finite element software. The properties of the nanocomposites are investigated by considering the interphase zone between carbon nanofillers and matrix. The effects of different volume fractions, geometrical parameters, and orientations of the nanofillers on the elastic and thermal characteristics of the nanocomposites are studied considering both cohesive interaction and perfect bonding between the fillers and matrix. Moreover, the effects of applying strain on the effective thermal conductivity of the representative volume elements are analyzed. The results reveal that both stress–strain curves and thermal conductivity coefficients of the nanocomposites are following similar trends vs. the changes of the volume fractions as well as the geometries and orientations of the coiled carbon nanotubes. Analysis of the tensile toughness of all samples reveals that it is affected by both stress and the number of fillers in the representative volume element. In addition, thermal-displacement analysis shows that thermal conductivity coefficient decreases by increasing the applied strain on the representative volume element, while the intensity of decrease of the nanocomposite thermal conductivity depends on the volume fraction and interaction of the nanofillers and interphase zone. Finally, crashworthiness analysis of the nanocomposite material proves that they are appropriate candidates for absorbing energy under impact loadings in comparison to metals.
Common Knowledge? Public Understanding of Climate Change in Newcastle, Australia
Authors: Bulkeley Harriet
Published: November 2019

This paper argues that public understanding of climate change not only involves knowledge of its physical processes, but also encompasses wider issues concerning the relation between society and nature. It examines the conclusions of previous research, and assumptions made within the policy community concerning public understanding of climate change. It is argued that in each case, in accordance with the information deficit model, recorded levels of ignorance are seen as a barrier to effective public involvement in the policy process. This view is challenged by research findings from Newcastle, Australia. Public understanding of global environmental issues drew not only on scientific information, but also on local knowledges, values, and moral responsibilities. Further, respondents connected the issue to their communities, and suggested that individual action is morally sanctioned, despite concerns for the efficacy of such action and the lack of government or industry support. Where institutional realignment has occurred to provide renewable energy to householders, public involvement has been forthcoming. These findings suggest that rather than focus on the provision of information, policy attention should be directed to the social and institutional barriers that act to constrain public involvement in addressing global environmental issues.
Approach to the Assessment and Management of Pediatric Patients With Atopic Dermatitis: A Consensus Document. Section IV: Consensus Statements on the Assessment and Management of Pediatric Atopic Dermatitis
Authors: Lansang Perla , Lara-Corrales Irene , Bergman James N. , Hong Chih-ho , Joseph Marissa , Kim Vy H.D. , Lam Joseph M. , Landells Ian , Marcoux Danielle , Prajapati Vimal H. , Ramien Michele L. , Spring Shanna
Published: November 2019

This document is intended to provide practical guidance to physicians treating pediatric atopic dermatitis (AD), especially dermatologists, pediatricians, allergists, and other health-care professionals. The recommendations contained here were formalized based on a consensus of 12 Canadian pediatric dermatologists, dermatologists, pediatricians, and pediatric allergists with extensive experience managing AD in the pediatric population. A modified Delphi process was adopted with iterative voting on a 5-point Likert scale, with a prespecified agreement cutoff of 75%. Topic areas addressed in the 17 consensus statements reflect areas of practical management, including counselling, assessment, comorbidity management, and therapy.
Maximizing participation from online survey panel members
Authors: Brosnan Kylie , Kemperman Astrid , Dolnicar Sara
Published: November 2019

Low survey participation from online panel members is a key challenge for market and social researchers. We identify 10 key drivers of panel members’ online survey participation from a qualitative study and then determine empirically using a stated choice experiment the relative importance of each of those drivers at aggregate and segment levels. We contribute to knowledge on survey participation by (a) eliciting key drivers of survey participation by online panel members, (b) determining the relative importance of each driver, and (c) accounting for heterogeneity across panel members in the importance assigned to drivers. Findings offer immediate practical guidance to market and social researchers on how to increase participation in surveys using online panels.
Machine learning in secondary progressive multiple sclerosis: an improved predictive model for short-term disability progression
Authors: Law Marco TK , Traboulsee Anthony L , Li David KB , Carruthers Robert L , Freedman Mark S , Kolind Shannon H , Tam Roger
Published: November 2019

Background

Enhanced prediction of progression in secondary progressive multiple sclerosis (SPMS) could improve clinical trial design. Machine learning (ML) algorithms are methods for training predictive models with minimal human intervention.

Objective

To evaluate individual and ensemble model performance built using decision tree (DT)-based algorithms compared to logistic regression (LR) and support vector machines (SVMs) for predicting SPMS disability progression.

Methods

SPMS participants ( n = 485) enrolled in a 2-year placebo-controlled (negative) trial assessing the efficacy of MBP8298 were classified as progressors if a 6-month sustained increase in Expanded Disability Status Scale (EDSS) (≥1.0 or ≥0.5 for a baseline of ≤5.5 or ≥6.0 respectively) was observed. Variables included EDSS, Multiple Sclerosis Functional Composite component scores, T2 lesion volume, brain parenchymal fraction, disease duration, age, and sex. Area under the receiver operating characteristic curve (AUC) was the primary outcome for model evaluation.

Results

Three DT-based models had greater AUCs (61.8%, 60.7%, and 60.2%) than independent and ensemble SVM (52.4% and 51.0%) and LR (49.5% and 51.1%).

Conclusion

SPMS disability progression was best predicted by non-parametric ML. If confirmed, ML could select those with highest progression risk for inclusion in SPMS trial cohorts and reduce the number of low-risk individuals exposed to experimental therapies.
Assessment of Antibiotic Prescribing Patterns at Outpatient Pharmacy Using World Health Organization Prescribing Indicators
Authors: Yimenu Dawit Kumilachew , Emam Abdurazak , Elemineh Endilik , Atalay Wagaye
Published: November 2019

Background: Overuse of antibiotics is a common problem in health care, which leads to unnecessary expenditure on drugs, raised risk of adverse reactions, and the development of antimicrobial resistance. Inappropriate prescribing habits lead to ineffective and unsafe treatment, worsening of disease and increment of health care costs. The aim of this study was to assess antibiotic prescribing patterns using World Health Organization prescribing indicators at the outpatient Pharmacy Department of University of Gondar referral hospital, Gondar, Northwest Ethiopia. Methods: A retrospective cross-sectional study was conducted. One-year prescription data was collected from prescription and prescription registration books retained at the pharmacy store. World Health Organization/International Network of Rational Use of Drugs prescribing indicators were utilized to measure rational use of drugs with due focus on antibiotics prescribing patterns. The collected data was analyzed using SPSS version 20. Results and Discussion: A total of 968 drugs were prescribed from 600 patient encounters. The average number of drugs per encounter was 1.6. The percentage of encounters in which an antibiotics and injections were prescribed was 69.7% and 6.3% respectively. Amoxicillin (28.5%) followed by ciprofloxacin (12%) and metronidazole(11.1%) were the most commonly prescribed antibiotics. The percentage of drugs prescribed from essential drugs list and by generic name was 95.3% and 96%, respectively. Rate of antibiotics prescribing showed deviation from the standard recommended by World Health Organization whereas polypharmacy, injectable prescribing pattern, uses of brand names, and prescription of drugs from the National Essential Drugs List were not found to be a significant problem though there were slight deviations from the standard. Conclussion: Interventions aimed at improving the antibiotic prescribing patterns need to be implemented so as to prevent the inappropriate use of antibiotics and avoid further complications.
Indian business in the colonial and postcolonial period: Quest for hegemonic influence over Indian society
Authors: Mukherjee Aditya
Published: November 2019

This paper studies how the Indian business class, which from being among the most advanced in the world, was crushed in the colonial period and how in the colonial period itself, it made major attempts to fight back and re-establish itself. This it did by aligning with the Indian national movement and evolving a critique of imperialism. It also discusses how the business class positioned itself politically and ideologically in such a manner during the national movement and in the early years after independence that its influence over Indian society as a whole remained considerable despite a major offensive from the Left. This involved a complex enmeshing of societal interest with their long-term class interest. However, soon after the initial years of independence, the business class increasingly failed, except on a few occasions, to demonstrate a long-term view of society which would also be in their long-term interest.1
Reconstruction and analysis of a Kluyveromyces marxianus genome-scale metabolic model
Authors: Marcišauskas Simonas , Ji Boyang , Nielsen Jens
Published: November 2019

Background

Kluyveromyces marxianus is a thermotolerant yeast with multiple biotechnological potentials for industrial applications, which can metabolize a broad range of carbon sources, including less conventional sugars like lactose, xylose, arabinose and inulin. These phenotypic traits are sustained even up to 45 °C, what makes it a relevant candidate for industrial biotechnology applications, such as ethanol production. It is therefore of much interest to get more insight into the metabolism of this yeast. Recent studies suggested, that thermotolerance is achieved by reducing the number of growth-determining proteins or suppressing oxidative phosphorylation. Here we aimed to find related factors contributing to the thermotolerance of K. marxianus.

Results

Here, we reported the first genome-scale metabolic model of Kluyveromyces marxianus, iSM996, using a publicly available Kluyveromyces lactis model as template. The model was manually curated and refined to include the missing species-specific metabolic capabilities. The iSM996 model includes 1913 reactions, associated with 996 genes and 1531 metabolites. It performed well to predict the carbon source utilization and growth rates under different growth conditions. Moreover, the model was coupled with transcriptomics data and used to perform simulations at various growth temperatures.

Conclusions

K. marxianus iSM996 represents a well-annotated metabolic model of thermotolerant yeast, which provides a new insight into theoretical metabolic profiles at different temperatures of K. marxianus. This could accelerate the integrative analysis of multi-omics data, leading to model-driven strain design and improvement.
The effect of alignment uncertainty, substitution models and priors in building and dating the mammal tree of life
Authors: Du Yan , Wu Shaoyuan , Edwards Scott V. , Liu Liang
Published: November 2019

Background

The flood of genomic data to help build and date the tree of life requires automation at several critical junctures, most importantly during sequence assembly and alignment. It is widely appreciated that automated alignment protocols can yield inaccuracies, but the relative impact of various sources error on phylogenomic analysis is not yet known. This study employs an updated mammal data set of 5162 coding loci sampled from 90 species to evaluate the effects of alignment uncertainty, substitution models, and fossil priors on gene tree, species tree, and divergence time estimation. Additionally, a novel coalescent likelihood ratio test is introduced for comparing competing species trees against a given set of gene trees.

Results

The aligned DNA sequences of 5162 loci from 90 species were trimmed and filtered using trimAL and two filtering protocols. The final dataset contains 4 sets of alignments - before trimming, after trimming, filtered by a recently proposed pipeline, and further filtered by comparing ML gene trees for each locus with the concatenation tree. Our analyses suggest that the average discordance among the coalescent trees is significantly smaller than that among the concatenation trees estimated from the 4 sets of alignments or with different substitution models. There is no significant difference among the divergence times estimated with different substitution models. However, the divergence dates estimated from the alignments after trimming are more recent than those estimated from the alignments before trimming.

Conclusions

Our results highlight that alignment uncertainty of the updated mammal data set and the choice of substitution models have little impact on tree topologies yielded by coalescent methods for species tree estimation, whereas they are more influential on the trees made by concatenation. Given the choice of calibration scheme and clock models, divergence time estimates are robust to the choice of substitution models, but removing alignments deemed problematic by trimming algorithms can lead to more recent dates. Although the fossil prior is important in divergence time estimation, Bayesian estimates of divergence times in this data set are driven primarily by the sequence data.
Increase of reactive oxygen species contributes to growth inhibition by fluconazole in Cryptococcus neoformans
Authors: Dbouk Nadir Hani , Covington Madison Bailey , Nguyen Kenny , Chandrasekaran Srikripa
Published: November 2019

Background

Cryptococcus neoformans, a basidiomycetous yeast, is a fungal pathogen that can colonize the lungs of humans causing pneumonia and fungal meningitis in severely immunocompromised individuals. Recent studies have implied that the antifungal drug fluconazole (FLC) can induce oxidative stress in C. neoformans by increasing the production of reactive oxygen species (ROS), as presence of the antioxidant ascorbic acid (AA) could reverse the inhibitory effects of FLC on C. neoformans. However, in Candida albicans, AA has been shown to stimulate the expression of genes essential for ergosterol biosynthesis. Hence, the contribution of ROS in FLC-mediated growth inhibition remains unclear.

Results

In order to determine whether counteracting ROS generated by FLC in C. neoformans can contribute to diminishing inhibitory effects of FLC, we tested three other antioxidants in addition to AA, namely, pyrrolidine dithiocarbamate (PDTC), retinoic acid (RA), and glutathione (GSH). Our data confirm that there is an increase in ROS in the presence of FLC in C. neoformans. Importantly, all four antioxidants reversed FLC-mediated growth inhibition of C. neoformans to various extents. We further verified the involvement of increased ROS in FLC-mediated growth inhibition by determining that ROS-scavenging proteins, metallothioneins (CMT1 and CMT2), contribute to growth recovery by PDTC and AA during treatment with FLC.

Conclusion

Our study suggests that ROS contributes to FLC-mediated growth inhibition and points to a complex nature of antioxidant-mediated growth rescue in the presence of FLC.
Prevalence and antibiotic susceptibility patterns of enteric bacterial pathogens in human and non-human sources in an urban informal settlement in Cape Town, South Africa
Authors: Kalule John Bosco , Smith Anthony M. , Vulindhlu Mjikisile , Tau Nomsa P. , Nicol Mark P. , Keddy Karen H. , Robberts Lourens
Published: November 2019

Background

In light of rampant childhood diarrhoea, this study investigated bacterial pathogens from human and non-human sources in an urban informal settlement.

Meat from informal abattoirs (n = 85), river water (n = 64), and diarrheic stool (n = 66) were collected between September 2015 and May 2016. A duplex real-time PCR, gel-based PCR, and CHROMagar™STEC were used to screen Tryptic Soy Broth (TSB) for diarrheicE. coli. Standard methods were used to screen for other selected food and waterborne bacterial pathogens.

Results

Pathogens isolated from stool, meat, and surface water includedSalmonella enterica(6, 5, 0%),Plesiomonas shigelloides(9, 0, 17%),Aeromonas sobria(3, 3, 0%),Campylobacter jejuni(5, 5, 0%),Shigella flexneri(17, 5, 0%),Vibrio vulnificus(0, 0, 9%), and diarrheicE. coli(21, 3, 7%) respectively. All the isolates were resistant to trimethoprim–sulphamethoxazole.

Conclusions

There was a high burden of drug resistant diarrheal pathogens in the stool, surface water and meat from informal slaughter. Integrated control measures are needed to ensure food safety and to prevent the spread of drug resistant pathogens in similar settings.
Bacterial co-infection of the respiratory tract in ventilated children with bronchiolitis; a retrospective cohort study
Authors: Wiegers Hanke M. G. , van Nijen Lisa , van Woensel Job B. M. , Bem Reinout A. , de Jong Menno D. , Calis Job C. J.
Published: November 2019

Background

Viral bronchiolitis is the most common cause of respiratory failure requiring invasive ventilation in young children. Bacterial co-infections may complicate and prolong paediatric intensive care unit (PICU) stay. Data on prevalence, type of pathogens and its association with disease severity are limited though. These data are especially important as bacterial co-infections may be treated using antibiotics and could reduce disease severity and duration of PICU stay. We investigated prevalence of bacterial co-infection and its association with disease severity and PICU stay.

Methods

Retrospective cohort study of the prevalence and type of bacterial co-infections in ventilated children performed in a 14-bed tertiary care PICU in The Netherlands. Children less than 2 years of age admitted between December 2006 and November 2014 with a diagnosis of bronchiolitis and requiring invasive mechanical ventilation were included. Tracheal aspirates (TA) and broncho-alveolar lavages (BAL) were cultured and scored based on the quantity of bacteria colony forming units (CFU) as: co-infection (TA > 10^5/BAL > 10^4 CFU), low bacterial growth (TA < 10^5/BAL < 10^4 CFU), or negative (no growth). Duration of mechanical ventilation and PICU stay were collected using medical records and compared against the presence of co-infection using univariate and multivariate analysis.

Results

Of 167 included children 63 (37.7%) had a bacterial co-infection and 67 (40.1%) low bacterial growth. Co-infections occurred within 48 h from intubation in 52 out 63 (82.5%) co-infections. H.influenza (40.0%), S.pneumoniae (27.1%), M.catarrhalis (22.4%), and S.aureus (7.1%) were the most common pathogens. PICU stay and mechanical ventilation lasted longer in children with co-infections than children with negative cultures (9.1 vs 7.7 days, p = 0.04 and 8.1vs 6.5 days, p = 0.02).

Conclusions

In this large study, bacterial co-infections occurred in more than a third of children requiring invasive ventilation for bronchiolitis and were associated with longer PICU stay and mechanical ventilation. These findings support a clinical trial of antibiotics to test whether antibiotics can reduce duration of PICU stay.
Identification of a novel mutation of NOG in family with proximal symphalangism and early genetic counseling
Authors: Ma Cong , Liu Lv , Wang Fang-Na , Tian Hai-Shen , Luo Yan , Yu Rong , Fan Liang-Liang , Li Ya-Li
Published: November 2019

Background

Proximal symphalangism is a rare disease with multiple phenotypes including reduced proximal interphalangeal joint space, symphalangism of the 4th and/or 5th finger, as well as hearing loss. At present, at least two types of proximal symphalangism have been identified in the clinic. One is proximal symphalangism-1A (SYM1A), which is caused by genetic variants inNoggin(NOG), another is proximal symphalangism-1B (SYM1B), which is resulted fromGrowth Differentiation Factor 5(GDF5) mutations.

Case presentation

Here, we reported a Chinese family with symphalangism of the 4th and/or 5th finger and moderate deafness. The proband was a 13-year-old girl with normal intelligence but symphalangism of the 4th finger in the left hand and moderate deafness. Hearing testing and inner ear CT scan suggested that the proband suffered from structural deafness. Family history investigation found that her father (II-3) and grandmother (I-2) also suffered from hearing loss and symphalangism. Target sequencing identified a novel heterozygousNOGmutation, c.690C > G/p.C230W, which was the genetic lesion of the affected family. Bioinformatics analysis and public databases filtering further confirmed the pathogenicity of the novel mutation. Furthermore, we assisted the family to deliver a baby girl who did not carry the mutation by genetic counseling and prenatal diagnosis using amniotic fluid DNA sequencing.

Conclusion

In this study, we identified a novelNOGmutation (c.690C > G/p.C230W) by target sequencing and helped the family to deliver a baby who did not carry the mutation. Our study expanded the spectrum ofNOGmutations and contributed to genetic diagnosis and counseling of families with SYM1A.
mHealth communication to strengthen postnatal care in rural areas: a systematic review
Authors: Mbuthia Florence , Reid Marianne , Fichardt Annali
Published: November 2019

Background

Postnatal care (PNC) in rural areas is characterised by low uptake, with possible effect on maternal and neonatal mortality rates. Mobile health (mHealth) communication has been proposed to promote the uptake of health services; however, there is limited information on how mHealth can strengthen PNC in rural areas. The objective of this review was to gather the best available evidence regarding mHealth communication to strengthen PNC in rural areas.

Methods

Studies published between 1 January 2008 and 31 August 2018 were searched in electronic databases hosted by EBSCO Host. Reference list checking and contact with authors were also done. Critical appraisal of the eligible studies was also done.

Results

The results of 11 articles were synthesised to report the determinants of PNC uptake. Determinants were aligned to the Integrative Model of Behaviural Prediction (IMBP). One-way mobile phone messaging was the most common type of mHealth communication used. mHealth communication influenced mothers’ intentions, skills, and environmental constraints associated with uptake of PNC. Intentions were influenced by attitudes, perceived norms and self-efficacy. Positive attitudes, as well as changed attitudes toward PNC practices were observed. Perceived norms that were enhanced were delivery at a health facility with immediate PNC, seeking of reinforcement and professional health support of newborn care practices, and male partner support. Improved self-efficacy was demonstrated by mothers who attended scheduled appointments and they were confident with regard to newborn care practices. Skills for PNC that were improved included cord care, thermal care, appropriate breastfeeding and problem-solving. The environmental constraints faced and which were addressed in the studies included inaccessibility, unavailability and unaffordability of PNC services in rural areas.

Conclusions

Results from the literature included in this study show that one-way mobile phone messaging is the common type of mHealth communication used to strengthen PNC in rural areas. mHealth communication can influence intentions, skills and environmental constraints as determinants of PNC uptake. mHealth communication is recommended to strengthen PNC in rural areas. To widen the evidence, more studies in the field of mHealth communication that report a variety of both maternal and neonatal outcomes are needed.
LncRNA WT1-AS up-regulates p53 to inhibit the proliferation of cervical squamous carcinoma cells
Authors: Zhang Yunxia , Na Renhua , Wang Xinling
Published: November 2019

Background

It has been reported that the development of cervical squamous cell carcinoma (CSCC) requires the involvement of a large number of lncRNAs. In a recent study lncRNA, WT1-AS was been characterized as a tumor-suppressive lncRNA in gastric cancer. In our study we aim to explore the involvement of WT1-AS in CSCC.

Methods

Seventy-six CSCC patients (20 to 63 years, 40.1 ± 6.1 year) from the 233 CSCC patients who were admitted by the Affiliated Tumour Hospital of Xinjiang Medical University between august 2010 and January 2014. RT-qPCR, cell proliferation rate measurement, cell transfection, and western blot were carried out to analyze the samples.

Results

We found that HPV infection failed to affect WT1-AS expression in CSCC tissues, while WT1-AS was down-regulated in CSCC tissues compared with non-cancer tissues. P53 was also down-regulated in CSCC tissues and positively correlated with WT1-AS. Analysis of the survival of CSCC patients revealed that low levels of WT1-AS were accompanied by poor survival. Significantly up-regulated p53 was observed after WT1-AS over-expression in CSCC cells, while p53 over-expression failed to affect WT1-AS. P53 and WT1-AS over-expression resulted in the inhibited proliferation of CSCC cells.

Conclusion

Therefore, WT1-AS is down-regulated in CSCC and it may inhibit CSCC cell proliferation at least partially by up-regulating p53.
Role of protein arginine methyltransferase 5 in group 3 (MYC-driven) Medulloblastoma
Authors: Chaturvedi Nagendra K. , Mahapatra Sidharth , Kesherwani Varun , Kling Matthew J. , Shukla Mamta , Ray Sutapa , Kanchan Ranjana , Perumal Naveenkumar , McGuire Timothy R. , Sharp J. Graham , Joshi Shantaram S. , Coulter Don W.
Published: November 2019

Background

MYC amplification or overexpression is common in Group 3 medulloblastoma and is associated with the worst prognosis. Recently, protein arginine methyl transferase (PRMT) 5 expression has been closely associated with aberrant MYC function in various cancers, including brain tumors such as glioblastoma. However, the role of PRMT5 and its association with MYC in medulloblastoma have not been explored. Here, we report the role of PRMT5 as a novel regulator of MYC and implicate PRMT5 as a potential therapeutic target in MYC-driven medulloblastoma.

Methods

Expression and association between PRMT5 and MYC in primary medulloblastoma tumors were investigated using publicly available databases. Expression levels of PRMT5 protein were also examined using medulloblastoma cell lines and primary tumors by western blotting and immunohistochemistry, respectively. Using MYC-driven medulloblastoma cells, we examined the physical interaction between PRMT5 and MYC by co-immunoprecipitation and co-localization experiments. To determine the functional role of PRMT5 in MYC-driven medulloblastoma, PRMT5 was knocked-down in MYC-amplified cells using siRNA and the consequences of knockdown on cell growth and MYC expression/stability were investigated. In vitro therapeutic potential of PRMT5 in medulloblastoma was also evaluated using a small molecule inhibitor, EPZ015666.

Results

We observed overexpression of PRMT5 in MYC-driven primary medulloblastoma tumors and cell lines compared to non-MYC medulloblastoma tumors and adjacent normal tissues. We also found that high expression of PRMT5 is inversely correlated with patient survival. Knockdown of PRMT5 using siRNA in MYC-driven medulloblastoma cells significantly decreased cell growth and MYC expression. Mechanistically, we found that PRMT5 physically associated with MYC by direct protein-protein interaction. In addition, a cycloheximide chase experiment showed that PRMT5 post-translationally regulated MYC stability. In the context of therapeutics, we observed dose-dependent efficacy of PRMT5 inhibitor EPZ015666 in suppressing cell growth and inducing apoptosis in MYC-driven medulloblastoma cells. Further, the expression levels of PRMT5 and MYC protein were downregulated upon EPZ015666 treatment. We also observed a superior efficacy of this inhibitor against MYC-amplified medulloblastoma cells compared to non-MYC-amplified medulloblastoma cells, indicating specificity.

Conclusion

Our results reveal the regulation of MYC oncoprotein by PRMT5 and suggest that targeting PRMT5 could be a potential therapeutic strategy for MYC-driven medulloblastoma.
Residential immersive life skills programs for youth with disabilities: a case study of youth developmental trajectories of personal growth and caregiver perspectives
Authors: Kingsnorth Shauna , Rudzik Alanna E. F. , King Gillian , McPherson Amy C.
Published: November 2019

Background

Professional support in pediatric and rehabilitation care environments has been recommended as a means to build youth competence in life skills during their transition to adulthood. Life skills are the essential psychosocial competencies and interpersonal skills needed to manage one’s life. Residential immersive life skills (RILS) programs offer youth with physical disabilities enriched learning environments to acquire these skills. This study explored trajectories of personal growth in life skills and positive psychological outcomes among youth participating in a RILS program and related caregiver perspectives.

Method

Delivered by a multidisciplinary healthcare team,The Independence Programis an intensive summer program housed in a college residence that provides realistic experiences of living away from home for small groups of youth between 17 and 21 years of age who have congenital and/or acquired physical disabilities. Using a longitudinal case study and qualitative descriptive design, four youth and their parents/guardians participated in semi-structured interviews prior to, and then 1 month, and 3 to 4 months after the program. A conventional content analysis yielded chronological narratives for each youth and caregiver dyad of their experiences, perceptions and outcomes over time. These narratives were further summarized using a ‘line of development’ perspective to describe individual developmental trajectories of personal growth.

Results

All four of the youth returned from the program with positive reports about the new life skills acquired and new behaviours they engaged in. These positive reports generally continued post-program, albeit with differing trajectories unique to each youth and varying levels of congruence with their caregivers’ readiness to support, accommodate and facilitate these changes. Caregivers differed in their capacity to shift in their parenting role to support consolidation of youth life skill competencies following program participation.

Conclusions

RILS programs can be transformative. Varied youth trajectories identified significant personal growth through enhanced self-determination, self-efficacy and self-advocacy. Congruence in youth and caregiver perceptions of post-program changes was an important transactional factor. Professional support addressing caregiver needs may be beneficial to facilitate developmentally appropriate shifts in parenting roles. This shift is central to a model of shared management whereby adolescents take on greater responsibility for their own care and life choices.
The moderating role of race/ethnicity and nativity in the relationship between perceived discrimination and overweight and obesity: results from the National Epidemiologic Survey on Alcohol and Related Conditions
Authors: Cuevas Adolfo G. , Ortiz Kasim , Ransome Yusuf
Published: November 2019

Background

The overweight/obesity epidemic is a public health issue in the United States (US), that disproportionately affect certain racial/ethnic minority groups. Perceived discrimination has been implicated as a health risk factor. However, research on race/ethnicity, perceived discrimination, and obesity has been mixed. Researchers suggest that perceptions of discrimination may be dependent upon nativity status. This study evaluated the role that nativity status and race/ethnicity play in the relationship between perceived discrimination and overweight/obesity.

Methods

We used Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (2004–2005) [N = 33,319]). Multinomial logistic regression assessed a three-way interaction (perceived discrimination × race/ethnicity × nativity) on overweight and obesity, adjusting for sociodemographic factors and health-related behaviors.

Results

The three-way interaction was significant for overweight [F (17, 49) = 3.35; p < 0.001] and obesity [F (17, 49) = 5.05; p < 0.001]. Among US-born individuals, US-born non-Hispanic Blacks had a decreased risk of being obese compared to US-born non-Hispanic Whites at mean levels of perceived discrimination [aRRR = 0.71; 95% CI (0.51–0.98); p = 0.04). Among foreign-born individuals, foreign-born South Americans had an increased risk of being overweight at mean levels of perceived discrimination compared to foreign-born non-Hispanic Whites [aRRR = 8.07; 95% CI (1.68–38.77); p = 0.01], whereas foreign-born Dominicans had a decreased risk of being obese compared to foreign-born non-Hispanic Whites [aRRR = 0.05; 95% CI (0.01–0.20); p < 0.001].

Conclusion

Perceived racial discrimination is a risk factor for overweight/obesity for certain groups. Race/ethnicity and nativity may play important roles in the relationship between perceived discrimination and overweight/obesity. Future research is needed to identify the behavioral and psychological pathways that link perceived discrimination and overweight/obesity.
Treatment outcomes of tuberculous meningitis in adults: a systematic review and meta-analysis
Authors: Wang Ming-Gui , Luo Lan , Zhang Yunxia , Liu Xiangming , Liu Lin , He Jian-Qing
Published: November 2019

Background

Tuberculous meningitis is the most devastating presentation of disease with Mycobacterium tuberculosis. We sought to evaluate treatment outcomes for adult patients with this disease.

Methods

The Ovid MEDLINE, EMBASE, Cochrane Library and Web of Science databases were searched to identify all relevant studies. We pooled appropriate data to estimate treatment outcomes at the end of treatment and follow-up.

Results

Among the articles identified, 22 met our inclusion criteria, with 2437 patients. In a pooled analysis, the risk of death was 24.7% (95%CI: 18.7–31.9). The risk of neurological sequelae among survivors was 50.9% (95%CI: 40.2–61.5). Patients diagnosed in stage III or human immunodeficiency virus (HIV) positive were significantly more likely to die (64.8, 53.4% respectively) during treatment. The frequency of cerebrospinal fluid (CSF) acid-fast-bacilli smear positivity was 10.0% (95% CI 5.5–17.6), 23.8% (15.2–35.3) for CSF culture positivity, and 22.3% (17.8–27.5) for CSF polymerase chain reaction positivity. We found that the headache, fever, vomiting, and abnormal chest radiograph were the most common symptoms and diagnostic findings among tuberculous meningitis patients.

Conclusions

Despite anti-tuberculosis treatment, adult tuberculous meningitis has very poor outcomes. The mortality rate of patients diagnosed in stage III or HIV co-infection increased significantly during treatment.
Difficult iatrogenic bile duct injuries following different types of upper abdominal surgery: report of three cases and review of literature
Authors: Lubikowski Jerzy , Piotuch Bernard , Stadnik Anna , Przedniczek Marta , Remiszewski Piotr , Milkiewicz Piotr , Silva Michael A. , Wojcicki Maciej
Published: November 2019

Background

Iatrogenic bile duct injuries (BDIs) are mostly associated with laparoscopic cholecystectomy but may also occur following gastroduodenal surgery or liver resection. Delayed diagnosis of type of injury with an ongoing biliary leak as well as the management in a non-specialized general surgical units are still the main factors affecting the outcome.

Case presentation

Herein we present three types of BDIs (Bismuth type I, IV and V) following three different types of upper abdominal surgery, ie. Billroth II gastric resection, laparoscopic cholecystectomy and left hepatectomy. All of them were complex injuries with complete bile duct transections necessitating surgical treatment. All were also very difficult to treat mainly because of a delayed diagnosis of type of injury, associated biliary leak and as a consequence severe inflammatory changes within the liver hilum. The treatment was carried out in our specialist hepatobiliary unit and first focused on infection and inflammation control with adequate biliary drainage. This was followed by a delayed surgical repair with the technique which had to be tailored to the type of injury in each case.

Conclusion

We emphasize that staged and individualized treatment strategy is often necessary in case of a delayed diagnosis of complex BDIs presenting with a biliary leak, inflammatory intraabdominal changes and infection. Referral of such patients to expert hepatobiliary centres is crucial for the outcome.
Identification and characterization of the Cucurbitacins, a novel class of small-molecule inhibitors of Tropomyosin receptor kinase a
Authors: Zhong Yueling , Xu Hong , Zhong Yi , Zhang Xuemiao , Zeng Ting , Li Limei , Xu Gaojie , Li Minhui , Liu Jin , Yang Tai
Published: November 2019

Background

NGF-TrkA is well known to play a key role in propagating and sustaining pruritogenic signals, which form the pathology of chronic pruritus. Inhibition of NGF-TrkA is a known strategy for the treatment of pruritus. In the present paper, we describe the identification, in vitro characterization, structure–activity analysis, and inhibitory evaluation of a novel TrkA inhibitory scaffold exemplified by Cucurbitacins (Cus).

Methods

Cus were identified as TrkA inhibitors in a large-scale kinase library screen. To obtain structural models of Cus as TrkA inhibitors, AutoDock was used to explore their binding to TrkA. Furthermore, PC12 cell culture systems have been used to study the effects of Cus and traditional Chinese medicinal plants (Tian Gua Di and bitter gourd leaf) extracts on the kinase activity of TrkA.

Results

Cus block the phosphorylation of TrkA on several tyrosine sites, including Tyr490, Tyr674/675, and Tyr785, and inhibit downstream Akt and MAPK phosphorylation in response to NGF in PC12 cell model systems. Furthermore, traditional Chinese medicinal plants (Tian Gua Di and bitter gourd leaf) containing Cu extracts were shown to inhibit the phosphorylation of TrkA and Akt. These data reveal mechanisms, at least partly, of the anti-pruritus bioactivity of Cus.

Conclusion

Taken together, with the recent discovery of the important role of TrkA as a therapeutic target, Cus could be the basis for the design of improved TrkA kinase inhibitors, which could someday help treat pruritus.
The power of language-concordant care: a call to action for medical schools
Authors: Molina Rose L. , Kasper Jennifer
Published: November 2019

We live in a world of incredible linguistic diversity; nearly 7000 languages are spoken globally and at least 350 are spoken in the United States. Language-concordant care enhances trust between patients and physicians, optimizes health outcomes, and advances health equity for diverse populations. However, historical and contemporary trauma have impaired trust between communities of color, including immigrants with limited English proficiency, and physicians in the U.S. Threats to informed consent among patients with limited English proficiency persist today. Language concordance has been shown to improve care and serves as a window to broader social determinants of health that disproportionately yield worse health outcomes among patients with limited English proficiency. Language concordance is also relevant for medical students engaged in health care around the world. Global health experiences among medical and dental students have quadrupled in the last 30 years. Yet, language proficiency and skills to address cultural aspects of clinical care, research and education are lacking in pre-departure trainings. We call on medical schools to increase opportunities for medical language courses and integrate them into the curriculum with evidence-based teaching strategies, content about health equity, and standardized language assessments. The languages offered should reflect the needs of the patient population both where the medical school is located and where the school is engaged globally. Key content areas should include how to conduct a history and physical exam; relevant health inequities that commonly affect patients who speak different languages; cultural sensitivity and humility, particularly around beliefs and practices that affect health and wellbeing; and how to work in language-discordant encounters with interpreters and other modalities. Rigorous language assessment is necessary to ensure equity in communication before allowing students or physicians to use their language skills in clinical encounters. Lastly, global health activities in medical schools should assess for language needs and competency prior to departure. By professionalizing language competency in medical schools, we can improve patients’ trust in individual physicians and the profession as a whole; improve patient safety and health outcomes; and advance health equity for those we care for and collaborate with in the U.S. and around the world.
Assessing the implementation of a patient navigation intervention for colonoscopy screening
Authors: DeGroff Amy , Gressard Lindsay , Glover-Kudon Rebecca , Rice Ketra , Tharpe Felicia Solomon , Escoffery Cam , Gersten Joanne , Butterly Lynn
Published: November 2019

Background

A recent study demonstrated the effectiveness of the New Hampshire Colorectal Cancer Screening Program’s (NHCRCSP) patient navigation (PN) program. The PN intervention was delivered by telephone with navigators following a rigorous, six-topic protocol to support low-income patients to complete colonoscopy screening. We applied the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework to examine implementation processes and consider potential scalability of this intervention.

Methods

A mixed-methods evaluation study was conducted including 1) a quasi-experimental, retrospective, comparison group study examining program effectiveness, 2) secondary analysis of NHCRCSP program data, and 3) a case study. Data for all navigated patients scheduled and notified of their colonoscopy test date between July 1, 2012 and September 30, 2013 (N = 443) were analyzed. Researchers were provided in-depth call details for 50 patients randomly selected from the group of 443. The case study included review of program documents, observations of navigators, and interviews with 27 individuals including staff, patients, and other stakeholders.

Results

Program reach was state-wide, with navigators serving patients from across the state. The program successfully recruited patients from the intended priority population who met the established age, income, and insurance eligibility guidelines. Analysis of the 443 NHCRCSP patients navigated during the study period demonstrated effectiveness with 97.3% completing colonoscopy, zero missed appointments (no-shows), and 0.7% late cancellations. Trained and supervised nurse navigators spent an average of 124.3 min delivering the six-topic PN protocol to patients. Navigators benefited from a real-time data system that allowed for patient tracking, communication across team members, and documentation of service delivery. Evaluators identified several factors supporting program maintenance including consistent funding support from CDC, a strong program infrastructure, and partnerships.

Conclusions

Factors supporting implementation included funding for colonoscopies, use of registered nurses, a clinical champion, strong partnerships with primary care and endoscopy sites, fidelity to the PN protocol, significant intervention dose, and a real-time data system. Further study is needed to assess scalability to other locations.
Evidence-based care in high- and low-risk groups following whiplash injury: a multi-centre inception cohort study
Authors: Griffin Alexandra , Jagnoor Jagnoor , Arora Mohit , Cameron Ian D. , Kifley Annette , Sterling Michele , Kenardy Justin , Rebbeck Trudy
Published: November 2019

Background

Studies aimed at improving the provision of evidence-based care (EBC) for the management of acute whiplash injuries have been largely successful. However, whether EBC is broadly provided and whether delivery of EBC varies based on risk of non-recovery, is uncertain. Receiving EBC should improve recovery, though this relationship has yet to be established. Further, mitigating the effect of EBC is the relationship with the practitioner, a phenomenon poorly understood in WAD. This study aimed to determine the proportion of individuals with whiplash, at differing baseline risk levels, receiving EBC. This study also aimed to determine whether receiving EBC and the therapeutic relationship were associated with recovery at 3 months post injury.

Methods

Participants with acute whiplash were recruited from public hospital emergency departments, private physiotherapy practices, and State Insurance Regulatory Authority (SIRA) databases. Participants completed questionnaires at baseline (demographics, risk of non-recovery) and 3-months (treatment received, risk identification, therapeutic relationship) post injury. Primary health care providers (HCPs) treating these participants also completed questionnaires at 3-months. Recovery was defined as neck disability index ≤4/50 and global perceived effect of ≥4/5.

Results

Two-hundred and twenty-eight people with acute whiplash, and 53 primary care practitioners were recruited. The majority of the cohort reported receiving EBC, with correct application of the Canadian C-spine rule (74%), and provision of active treatments (e.g. 89% receiving advice) high. Non-recommended (passive) treatments were also received by a large proportion of the cohort (e.g. 50% receiving massage). The therapeutic relationship was associated with higher odds of recovery, which was potentially clinically significant (OR 1.34, 95% CI 1.18–1.62). EBC was not significantly associated with recovery.

Conclusions

Guideline-based knowledge and practice has largely been retained from previous implementation strategies. However, recommendations for routine risk identification and tailored management, and reduction in the provision of passive treatment have not. The therapeutic relationship was identified as one of several important predictors of recovery, suggesting that clinicians must develop rapport and understanding with their patients to improve the likelihood of recovery.