bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined quantitation of HMGA2 mRNA, microRNAs, and mitochondrial-DNA content enables the identification and typing of thyroid tumors in fine-needle aspiration smears
Authors: Titov Sergei E. , Ivanov Mikhail K. , Demenkov Pavel S. , Katanyan Gevork A. , Kozorezova Eugenia S. , Malek Anastasia V. , Veryaskina Yulia A. , Zhimulev Igor F.
Published: October 2019

Background

Analysis of molecular markers in addition to cytological analysis of fine-needle aspiration (FNA) samples is a promising way to improve the preoperative diagnosis of thyroid nodules. Nonetheless, in clinical practice, applications of existing diagnostic solutions based on the detection of somatic mutations or analysis of gene expression are limited by their high cost and difficulties with clinical interpretation.

The aim of our work was to develop an algorithm for the differential diagnosis of thyroid nodules on the basis of a small set of molecular markers analyzed by real-time PCR.

Methods

A total of 494 preoperative FNA samples of thyroid goiters and tumors from 232 patients with known histological reports were analyzed: goiter, 105 samples (50 patients); follicular adenoma, 101 (48); follicular carcinoma, 43 (28); Hürthle cell carcinoma, 25 (11); papillary carcinoma, 121 (56); follicular variant of papillary carcinoma, 80 (32); and medullary carcinoma, 19 (12). Total nucleic acids extracted from dried FNA smears were analyzed for five somatic point mutations and two translocations typical of thyroid tumors as well as for relative concentrations of HMGA2 mRNA and 13 microRNAs and the ratio of mitochondrial to nuclear DNA by real-time PCR. A decision tree–based algorithm was built to discriminate benign and malignant tumors and to type the thyroid cancer. Leave-p-out cross-validation with five partitions was performed to estimate prediction quality. A comparison of two independent samples by quantitative traits was carried out via the Mann–Whitney U test.

Results

A minimum set of markers was selected (levels of HMGA2 mRNA and miR-375, − 221, and -146b in combination with the mitochondrial-to-nuclear DNA ratio) and yielded highly accurate discrimination (sensitivity = 0.97; positive predictive value = 0.98) between goiters with benign tumors and malignant tumors and accurate typing of papillary, medullary, and Hürthle cell carcinomas. The results support an alternative classification of follicular tumors, which differs from the histological one.

Conclusions

The study shows the feasibility of the preoperative differential diagnosis of thyroid nodules using a panel of several molecular markers by a simple PCR-based method. Combining markers of different types increases the accuracy of classification.
Differentiating adults who think about self-harm from those who engage in self-harm: the role of volitional alcohol factors
Authors: Melson Ambrose J. , O’Connor Rory C.
Published: October 2019

Background

Self-harm, an act of self-poisoning or self-injury irrespective of motivation, is a major public health concern. Use of alcohol prior to or alongside acts of self-harm is common but little is known about the alcohol-related mechanisms of self-harm enaction. We utilised an ideation-to-action approach to clarify the extent to which volitional alcohol factors differentiated those who have thoughts of self-harm but do not act on them (self-harm ideation) and those who engage in self-harm (self-harm enaction).

Methods

Cross-sectional analyses of the baseline phase of the Health Lifestyle and Wellbeing study: 1546 adults (1079 female; Mean age = 34 y; 92% White) resident in Scotland completed measures of demographics, lifetime self-harm, volitional alcohol factors and psychosocial factors. Multinomial logistic regression compared those with a history of self-harm thoughts (‘ideation’,n = 297), self-harm acts (‘enaction’,n = 346) and ‘controls’ (n = 897) to identify volitional alcohol factors associated with self-harm enaction.

Results

Volitional alcohol factors differentiated those with a history of self-harm enaction from those with a history of self-harm ideation (as well as those with no history) in initial models adjusted for demographics and depressive symptoms: the self-harm enaction group reported stronger alcohol-related negative urgency (OR = 1.74, 95% CI 1.41–2.16,p < .001), more frequent heavy drinking (OR = 1.46, 95% CI 1.24–1.72,p < .001) and stronger expectancies that drinking alcohol leads to negative self-perceptions (OR = 1.33, 95% CI 1.03–1.72,p = 0.03) and markers of self-harm risk (OR = 1.64, 95% CI 1.18–2.30,p = 0.004). Alcohol-related negative urgency and heavy-drinking frequency continued to differentiate those in the self-harm enaction group from those in ideation group in multivariate models. Consistent with theoretical models positing phase-specific moderators of self-harm ideation and enaction, psychosocial factors (perceived stress, support, negative mood regulation expectancies) differentiated those with a history of self-harm ideation from those without but not those in the ideation and enaction groups.

Conclusions

Management of self-harm risk requires better understanding of alcohol-related mechanisms of self-harm enaction. Volitional alcohol factors may play a role in governing the translation of self-harm thoughts into self-harm acts.
Prevalence of psychological distress and associated factors among adult tuberculosis patients attending public health institutions in Dire Dawa and Harar cities, Eastern Ethiopia
Authors: Ayana Tegegn Mulatu , Roba Kedir Teji , Mabalhin Myrla Obejero
Published: October 2019

Background

In developing countries, the prevalence of psychological distress was higher among tuberculosis patients. Patients with tuberculosis infection were more prone to psychological distress than peoples without tuberculosis. However, little studies were conducted on psychological distress among tuberculosis patients in Ethiopia, particularly in the Eastern Ethiopian health institutions.

Methods

Institution-based cross-sectional study design was conducted. Based on the TB burden, four hospitals and six health centers were selected from Dire Dawa and Harar cities. Socio-demographic factors, psychological distress, TB related stigma experience, and alcohol use data were collected by face to face interview while TB and HIV related variables collected from TB registration book. All TB patients from the first month of TB treatment initiation through 6 were consecutively interviewed by trained data collectors from January to February 2018. The collected data were entered into Epi Data Version 3.1 software and exported into SPSS window version 20 for analysis. Bivariate and multivariate binary logistic regression was carried out. All variables withP-value ≤0.25 were taken into the multivariate model. Crude and adjusted odds ratios with a 95% confidence interval were estimated, and variables withP-value less than 0.05 in the final model were taken as significant predictors of psychological distress.

Results

The prevalence of psychological distress among tuberculosis in this study population was 63.3% (95% CI: 58.1, 68.1). Being from rural residence (AOR: 1. 98; 95% CI: 1.01,3.86), co-infection TB- HIV (AOR: 2.15; 95% CI:1.02, 4.56), presence of at least one chronic disease (AOR:3.04; 95% CI:1.59,5.79), experience of stigma (AOR: 1.71; 95% CI:1.01, 2.90), Pulmonary and MDR-TB (AOR:2.53; 95% CI:1.50,4.28) and smoking cigarette (AOR:2.53; 95% CI:1.06,6.03) were associated with psychological distress.

Conclusions

In this study, almost two-thirds of the tuberculosis patients had psychological distress. Chronic disease morbidity, HIV-TB co-infection and experienced TB related stigma were associated with psychological distress. Attention should be given to chronic diseases including HIV/AIDS diagnosis and referring to chronic disease units to prevent the impact on mental health. Consideration should be given for psychological distress and linking moderate to severe form of the disease to the Psychiatric clinics to hinder its effects.
Perception of asthma control among asthmatics seen inChest Clinic at Tertiary Hospital, Addis Ababa, Ethiopia
Authors: Gebremariam Tewodros H. , Sherman Charles B. , Schluger Neil W.
Published: October 2019

Background

Patient awareness of asthma severity is important for optimal asthma management. However, there is often a discrepancy between physician assessment of asthma control based on guidelines and patient discernment of control. We compared physician and patient perception of asthma control in a clinic population seen at a tertiary hospital in Addis Ababa, Ethiopia.

Methods

In this cross-sectional study, 182 consecutive patients with a physician diagnosis of asthma seen in Chest Clinic at Tikur Anbessa Specialized Hospital (TASH) between July and December 2015 were studied. Demographics, asthma symptoms, medication use in the past month, and self-perception of asthma control in the past 7 days were obtained from the clinic records. Physician assessed asthma control was based on the GINA asthma symptom control assessment tool. Lung function was measured using a Diagnostic EasyOne Plus model 2001 SN spirometer. The institutional review board approved the study protocol.

Results

Of the 182 subjects, 68.1% were female. The mean age was 52 ± 12 years, and the mean (SD) duration of asthma was 19.4 ± 12.7 years. Forty-four (24.2%) patients had physician determined well-controlled asthma and 138 (75.8%) patients had physician determined partly controlled/uncontrolled asthma. One hundred and fifty-one (83%) patients thought their asthma control was good. However, the degree of concordance between physician evaluation and patient perception of asthma control was low (kappa index = 0.09). On multivariate analysis, self-perceived poor asthma control was associated with any activity limitation due to asthma and inconsistent inhaled corticosteroid use.

Conclusion

In our study, the first of its kind in Ethiopia, a high percent of patients with physician determined well-controlled asthma has appropriate perception of their disease state. However, those patients with partly controlled/uncontrolled asthma had poor self-perception of their disease, emphasizing the need for further patient education. These conclusions may be especially useful in the care of asthmatics from other low-income countries.
Association between inflammatory bowel disease and chronic obstructive pulmonary disease: a systematic review and meta-analysis
Authors: Labarca Gonzalo , Drake Lauren , Horta Gloria , Jantz Michael A. , Mehta Hiren J. , Fernandez-Bussy Sebastian , Folch Erik , Majid Adnan , Picco Michael
Published: October 2019

Introduction

There is evidence of an association between inflammatory bowel disease (IBD) and lung conditions such as chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis explored the risk of new onset IBD in patients with COPD and new onset COPD in IBD patients.

Methods

We performed a systematic review of observational studies exploring the risk of both associations. Two independent reviewers explored the EMBASE, MEDLINE, LILACS and DOAJ databases, and the risk of bias was evaluated using the ROBBINS-I tool. Data from included studies was pooled in a random effect meta-analysis following a DerSimonian-Laird method. The quality of the evidence was ranked using GRADE criteria.

Results

Four studies including a pooled population of 1355 new cases were included. We found association between new onset IBD in COPD population. The risk of bias was low in most of them. Only one study reported tobacco exposure as a potential confounding factor. The pooled risk ratio (RR) for a new diagnosis of IBD in COPD patients was 2.02 (CI, 1.56 to 2.63),I2 = 72% (GRADE: low). The subgroup analyses for Crohn’s disease and ulcerative colitis yielded RRs of 2.29 (CI, 1.51 to 3.48;I2 = 62%), and 1.79 (CI, 1.39 to 2.29;I2 = 19%.), respectively.

Discussion

According to our findings, the risk of new onset IBD was higher in populations with COPD compared to the general population without this condition. Based on our analysis, we suggest a potential association between IBD and COPD; however, further research exploring the potential effect of confounding variables, especially cigarette smoking, is still needed.

Review register

(PROSPERO: CRD42018096624)
Spanish validation of female condom attitude scale and female condom use in Colombian young women
Authors: Pablo Vallejo-Medina , Carlos Eduardo Ramírez , Alejandro Saavedra-Roa Diego , Mayra Gómez-Lugo , Claudia Pérez-Durán
Published: October 2019

Background

Infection by HIV and other STIs and unplanned pregnancies are among the most serious problems associated with sexuality. Male and female condoms are the only dual-purpose devices to control both unplanned pregnancies and STIs, and studying people’s attitudes toward the use of these devices are excellent ways to predict their use. Therefore, the purpose of the present study was to adapt and validate the Female Condom Attitude Scale for Spanish language and to evaluate the use of female condoms in Colombian population.

Methods

For that purpose, a total of 387 Colombian women aged 23.68 years in average were asked to respond to the Female Condom Attitude Scale, the Sexual Opinion Survey, and the UCLA Multidimensional Condom Attitudes Scale.

Results

The use of female condom in Colombia is very low; only 5.10% of the surveyed women had used it at least once. On the other hand, results revealed a five-factor dimensionality (Sexual pleasure enhancement, Inconvenience, Improved prophylaxis, Sexual pleasure inhibition, and Insertion reluctance) with alphas between .81 and .96. The scale also showed adequate psychometric properties and criterion validity. No relationship was found between attitudes toward female condom and attitudes toward male condom.

Conclusions

The Spanish adaptation of the Female Condom Attitude Scale was found to be reliable and valid in a sample of young women.
The myth of menstruation: how menstrual regulation and suppression impact contraceptive choice
Authors: DeMaria Andrea L. , Sundstrom Beth , Meier Stephanie , Wiseley Abigail
Published: October 2019

Background

Women in the US have access to various hormonal contraceptive methods that can regulate menstruation. This study examined the attitudes and perceptions of reproductive-aged women toward contraceptive methods, including how menstrual regulation and suppression preferences influenced contraceptive choice.

Methods

Data collection used a mixed-methods approach, including 6 focus groups (n = 61), individual interviews (n = 18), and a web-based survey (n = 547).

Results

Participants described contraceptive method preferences that allowed monthly bleeding and daily control, expressing concerns about long-acting reversible contraception (LARC) because of decreased user involvement. Some participants noted LARC improved their menstrual control. Many participants felt menstruation was healthy, whereas suppression was abnormal and resulted in negative health outcomes. Though participants indicated LARC as beneficial (M = 4.99 ± 1.66), convenient (M = 5.43 ± 1.68), and healthy (M = 4.62 ± 1.69), they chose combined oral contraceptives due to convenience.

Conclusions

Findings suggest women need more information about menstrual regulation and suppression before selecting a contraceptive method, specifically in relation to LARC versus combined oral contraception. Framing menstrual suppression as healthy and natural may improve perceptions of long-term health consequences related to LARC. Providers should discuss menstrual suppression safety to ensure selection of contraceptive options aligning with women’s preferences and needs.
Infringement of the right to surgical informed consent: negligent disclosure and its impact on patient trust in surgeons at public general hospitals – the voice of the patient
Authors: Gabay Gillie , Bokek-Cohen Yaarit
Published: October 2019

Background

There is little dispute that the ideal moral standard for surgical informed consent calls for surgeons to carry out a disclosure dialogue with patients before they sign the informed consent form. This narrative study is the first to link patient experiences regarding the disclosure dialogue with patient-surgeon trust, central to effective recuperation and higher adherence.

Methods

Informants were 12 Israelis (6 men and 6 women), aged 29–81, who underwent life-saving surgeries. A snowball sampling was used to locate participants in their initial recovery process upon discharge.

Results

Our empirical evidence indicates an infringement of patients’ right to receive an adequate disclosure dialogue that respects their autonomy. More than half of the participants signed the informed consent form with no disclosure dialogue, and thus felt anxious, deceived and lost their trust in surgeons. Surgeons nullified the meaning of informed consent rather than promoted participants’ moral agency and dignity.

Discussion

Similarity among jarring experiences of participants led us to contend that the conduct of nullifying surgical informed consent does not stem solely from constraints of time and resources, but may reflect an underlying paradox preserving this conduct and leading to objectification of patients and persisting in paternalism. We propose a multi-phase data-driven model for informed consent that attends to patients needs and facilitates patient trust in surgeons.

Conclusions

Patient experiences attest to the infringement of a patient’s right to respect for autonomy. In order to meet the prima facie right of respect for autonomy, moral agency and dignity, physicians ought to respect patient’s needs. It is now time to renew efforts to avoid negligent disclosure and implement a patient-centered model of informed consent.
The "Begin Exploring Fertility Options, Risks and Expectations" (BEFORE) decision aid: development and alpha testing of a fertility tool for premenopausal breast cancer patients
Authors: Speller Brittany , Metcalfe Kelly , Kennedy Erin D. , Facey Marcia , Greenblatt Ellen , Scheer Adena S. , Warner Ellen , Joy Anil Abraham , Wright Frances C. , Baxter Nancy N.
Published: October 2019

Background

Premenopausal breast cancer patients are at risk of treatment-related infertility. Many patients do not receive sufficient fertility information before treatment. As such, our team developed and alpha tested the Begin Exploring Fertility Options, Risks, and Expectations decision aid (BEFORE DA).

Methods

The BEFORE DA development process was guided by the International Patient Decision Aids Standards and the Ottawa Decision Support Framework. Our team used integrated knowledge translation by collaborating with multiple stakeholders throughout the development process including breast cancer survivors, multi-disciplinary health care providers (HCPs), advocates, and cancer organization representatives. Based on previously conducted literature reviews and a needs assessment by our team – we developed a paper prototype. The paper prototype was finalized at an engagement meeting with stakeholders and created into a graphically designed paper and mirrored online decision aid. Alpha testing was conducted with new and previously engaged stakeholders through a questionnaire, telephone interviews, or focus group. Iterative reviews followed each step in the development process to ensure a wide range of stakeholder input.

Results

Our team developed an 18-page paper prototype containing information deemed valuable by stakeholders for fertility decision-making. The engagement meeting brought together 28 stakeholders to finalize the prototype. Alpha testing of the paper and online BEFORE DA occurred with 17 participants. Participants found the BEFORE DA usable, acceptable, and most provided enthusiastic support for its use with premenopausal breast cancer patients facing a fertility decision. Participants also identified areas for improvement including clarifying content/messages and modifying the design/photos. The final BEFORE DA is a 32-page paper and mirrored online decision aid (https://fertilityaid.rethinkbreastcancer.com). The BEFORE DA includes information on fertility, fertility options before/after treatment, values clarification, question list, next steps, glossary and reference list, and tailored information on the cost of fertility preservation and additional resources by geographic location.

Conclusion

The BEFORE DA, designed in collaboration with stakeholders, is a new tool for premenopausal breast cancer patients and HCPs to assist with fertility discussions and decision-making. The BEFORE DA helps to fill the information gap as it is a tool that HCPs can refer patients to for supplementary information surrounding fertility.
Feasibility analysis of conducting observational studies with the electronic health record
Authors: von Lucadou Marcel , Ganslandt Thomas , Prokosch Hans-Ulrich , Toddenroth Dennis
Published: October 2019

Background

The secondary use of electronic health records (EHRs) promises to facilitate medical research. We reviewed general data requirements in observational studies and analyzed the feasibility of conducting observational studies with structured EHR data, in particular diagnosis and procedure codes.

Methods

After reviewing published observational studies from the University Hospital of Erlangen for general data requirements, we identified three different study populations for the feasibility analysis with eligibility criteria from three exemplary observational studies. For each study population, we evaluated the availability of relevant patient characteristics in our EHR, including outcome and exposure variables. To assess data quality, we computed distributions of relevant patient characteristics from the available structured EHR data and compared them to those of the original studies. We implemented computed phenotypes for patient characteristics where necessary. In random samples, we evaluated how well structured patient characteristics agreed with a gold standard from manually interpreted free texts. We categorized our findings using the four data quality dimensions “completeness”, “correctness”, “currency” and “granularity”.

Results

Reviewing general data requirements, we found that some investigators supplement routine data with questionnaires, interviews and follow-up examinations. We included 847 subjects in the feasibility analysis (Study 1n = 411, Study 2n = 423, Study 3n = 13). All eligibility criteria from two studies were available in structured data, while one study required computed phenotypes in eligibility criteria. In one study, we found that all necessary patient characteristics were documented at least once in either structured or unstructured data. In another study, all exposure and outcome variables were available in structured data, while in the other one unstructured data had to be consulted. The comparison of patient characteristics distributions, as computed from structured data, with those from the original study yielded similar distributions as well as indications of underreporting. We observed violations in all four data quality dimensions.

Conclusions

While we found relevant patient characteristics available in structured EHR data, data quality problems may entail that it remains a case-by-case decision whether diagnosis and procedure codes are sufficient to underpin observational studies. Free-text data or subsequently supplementary study data may be important to complement a comprehensive patient history.
Public engagement in health technology assessment in Brazil: the case of the Trastuzumab public consultation
Authors: Carvalho Viviane Karoline da Silva , de Sousa Maria Sharmila Alina , Barreto Jorge Otávio Maia , da Silva Everton Nunes
Published: October 2019

Background

Public engagement in health technology assessment (HTA) is increasing worldwide. There are several forms of public engagement and it is not always possible to determine which stakeholders participate in the HTA process and how they contribute. Our objective was to investigate which types of social representatives contributed to the public consultation on the incorporation of Trastuzumab for early-stage breast cancer treatment within the public health system in Brazil, held in 2012 by the National Committee for Health Technology Incorporation (CONITEC).

Methods

A mixed methods approach was used to analyze social representativeness and the composition of the corpus from the public consultation, which consisted of 127 contributions. Three types of analysis were performed using IRaMuTeQ software: classic lexical analysis, descending hierarchical classification and specificities analysis. The contributions were clustered according to the main categories of discourse observed, into four social representation categories: 1) patient representation/advocacy; 2) pharmaceutical industry/advocacy; 3) healthcare professionals; and 4) individual contributions.

Results

Category 1 contained words related to increased survival due to use of the drug and a low score for words pertaining to studies on Trastuzumab. The word “safety” obtained a positive score only in category 2, which was also the only category that exhibited a negative score for the word “risk”. Category 3 displayed the lowest scores for “diagnosis” and “safety”. The word “efficacy” had a negative score only in category 4.

Conclusions

Each category exhibited different results for words related to health systems and to key concepts linked to HTA. Our analysis enabled the identification of the most prominent contributions for each category. Despite the promising results obtained, further research is needed to validate this software for use in analyzing public contributions.
Understanding competing discourses as a basis for promoting equity in primary health care
Authors: Blanchet Garneau Amélie , Browne Annette J. , Varcoe Colleen
Published: October 2019

Background

Globally, health inequities persist with effects on whole populations and the most profound effects on populations marginalized by poverty, discrimination and other forms of disadvantage. In the current neoliberal political-economic context, health inequities are produced and sustained by the inequitable distribution of social determinants of health and structural inequities such as discrimination and institutional racism. Even in the context of healthcare organizations with an explicit commitment to health equity, multiple intersecting discourses, such as ongoing efficiency discourses, and culturalist and racialized discourses, are in constant interaction with healthcare practices at the point of care and the organizational level, limiting providers’ and organizations’ capacities to address structural inequities. Attention to discourses that sustain inequities in health care is required to mitigate health inequities and related power differentials. In this paper, we present findings from a critical analysis of the relations among multiple discourses and healthcare practices within four Canadian primary health care clinics that have an explicit commitment to health equity.

Methods

Informed by critical theoretical perspectives and critical discourse analysis principles, we conducted an analysis of 31 in-depth interviews with clinic staff members. The analysis focused on the relations among discourses and healthcare practices, the ways in which competing discourses influence, reinforce, and challenge current practices, and how understanding these dynamics can be enlisted to promote health equity.

Results

We articulate the findings through three interrelated themes: equity-mandated organizations are positioned as the “other” in the health care system; discourses align with structures and policies to position equity at the margins of health care; staff and organizations navigate competing discourses through hybrid approaches to care.

Conclusions

This study points to the ways in which multiple discourses interact with healthcare organizations’ and providers’ practices and highlights the importance of structural changes at the systemic level to foster health equity at the point of care.
Economic valuation of informal care provided to people after a myocardial infarction in France
Authors: Rabier Hugo , Serrier Hassan , Schott Anne-Marie , Mewton Nathan , Ovize Michel , Nighoghossian Norbert , Duclos Antoine , Colin Cyrille
Published: October 2019

Background

The aim of this study was to estimate the mean cost per caregiver of informal care during the first year after myocardial infarction event in France.

Methods

We used theHandicap-SantéFrench survey carried out in 2008 to obtain data about MI survivors and their caregivers. After obtaining the total number of informal care hours provided by caregiver during the first year after MI event, we estimated the value of informal care using the proxy good method and the contingent valuation method.

Results

For MI people receiving informal care, an annual mean cost was estimated at €12,404 (SD = 13,012) with the proxy good method and €12,798 (SD = 13,425) with the contingent valuation method per caregiver during the first year after myocardial infarction event.

Conclusions

The present study suggests that informal care should be included more widely in economic evaluations in order not to underestimate the cost of diseases which induce disability.
The human gut bacteria Christensenellaceae are widespread, heritable, and associated with health
Authors: Waters Jillian L. , Ley Ruth E.
Published: October 2019

The Christensenellaceae, a recently described family in the phylum Firmicutes, is emerging as an important player in human health. The relative abundance of Christensenellaceae in the human gut is inversely related to host body mass index (BMI) in different populations and multiple studies, making its relationship with BMI the most robust and reproducible link between the microbial ecology of the human gut and metabolic disease reported to date. The family is also related to a healthy status in a number of other different disease contexts, including obesity and inflammatory bowel disease. In addition, Christensenellaceae is highly heritable across multiple populations, although specific human genes underlying its heritability have so far been elusive. Further research into the microbial ecology and metabolism of these bacteria should reveal mechanistic underpinnings of their host-health associations and enable their development as therapeutics.
Bacitracin resistance and enhanced virulence of Streptococcus suis via a novel efflux pump
Authors: Ma Jiale , Liu Jin , Zhang Yue , Wang Dan , Liu Runxia , Liu Guangjin , Yao Huochun , Pan Zihao
Published: October 2019

Background

Streptococcus suis is a prominent pathogen causing septicemia and meningitis in swine and humans. Bacitracin is used widely as a growth promoter in animal feed and to control the spread of necrotic enteritis in most developing countries. This study aimed to characterize a novel membrane transporter module Sst comprising SstE, SstF, and SstG for bacitracin resistance.

Results

Comparative genomics and protein homology analysis found a potential efflux pump SstFEG encoded upstream of well-known bacitracin-resistance genes bceAB and bceRS. A four-fold decrease in bacitracin susceptibility was observed in sstFEG deletion mutant comparing with S. suis wildtype strain CZ130302. Further studies indicated that the bacitracin tolerance mediated by SstFEG is not only independent of the BceAB transporter, but also regulated by the two-component system BceSR. Given that SstFEG are harbored by almost all virulent strains, but not in the avirulent strains, we managed to explore its potential role in bacterial pathogencity. Indeed, our results showed that SstFEG is involved in S. suis colonization and virulence in animal infection model by its potential competitive survival advantage against host bactericidal effect.

Conclusion

To our knowledge, this is the first study to functionally characterize the bacitracin efflux pump in S. suis to provide evidence regarding the important roles of the novel ABC transporter system SstFEG with respect to drug resistance and virulence.
Detecting total immunoglobulins in diverse animal species with a novel split enzymatic assay
Authors: Drikic Marija , Olsen Steven , De Buck Jeroen
Published: October 2019

Background

Total immunolobulin G concentration is a useful, albeit underutilized, diagnostic parameter for health assessments of non-domestic animal species, due to a lack of functional diagnostic tools. Traditional assays, including enzyme-linked immunosorbent assay or radial immunodiffusion, require development of specific reagents (e.g., polyclonal antisera and appropriate protocols) for each animal species, precluding wide and easy adoption in wildlife welfare. As an alternative, bacterial virulence factors able to bind IgGs in antigen-independent manner can be used. To further simplify the diagnostic procedure and increase the number of species recognized by an assay, in this study a recently developed Split Trehalase immunoglobulin assay (STIGA) with bIBPs as a sensing elements was used to detect antibodies in 29 species from 9 orders. Three bacterial immunoglobulin binding proteins (protein G, protein A and protein L) were incorporated into STIGA reagents to increase the number of species recognized.

Results

IgG concentrations were detected through glucose production and produced signals were categorized in 4 categories, from not active to strong signal. Activation was detected in almost all tested animal species, apart from birds. Incorporation of Protein G, Protein A and Protein L allowed detection of IgGs in 62, 15.5 and 6.9% of species with a strong signal, respectively. Assays combining 2 bacterial immunoglobulin binding proteins as sensing element generally gave poorer performance than assays with the same bacterial immunoglobulin binding proteins fused to both trehalase fragments.

Conclusions

STIGA assays have potential to be further developed into an easily adoptable diagnostic test for total amount of IgGs in almost any serum sample, independent of species.
Active roles of dysfunctional vascular endothelium in fibrosis and cancer
Authors: Hsu Tien , Nguyen-Tran Hieu-Huy , Trojanowska Maria
Published: October 2019

Chronic inflammation is the underlying pathological condition that results in fibrotic diseases. More recently, many forms of cancer have also been linked to chronic tissue inflammation. While stromal immune cells and myofibroblasts have been recognized as major contributors of cytokines and growth factors that foster the formation of fibrotic tissue, the endothelium has traditionally been regarded as a passive player in the pathogenic process, or even as a barrier since it provides a physical divide between the circulating immune cells and the inflamed tissues. Recent findings, however, have indicated that endothelial cells in fact play a crucial role in the inflammatory response. Endothelial cells can be activated by cytokine signaling and express inflammatory markers, which can sustain or exacerbate the inflammatory process. For example, the activated endothelium can recruit and activate leukocytes, thus perpetuating tissue inflammation, while sustained stimulation of endothelial cells may lead to endothelial-to-mesenchymal transition that contributes to fibrosis. Since chronic inflammation has now been recognized as a significant contributing factor to tumorigenesis, it has also emerged that activation of endothelium also occurs in the tumor microenvironment. This review summarizes recent findings characterizing the molecular and cellular changes in the vascular endothelium that contribute to tissue fibrosis, and potentially to cancer formation.
Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study
Authors: Chen Chi , Chen Yi , Weng Pan , Xia Fangzhen , Li Qin , Zhai Hualing , Wang Ningjian , Lu Yingli
Published: October 2019

Background

Low circulating vitamin D levels have been associated with increased risk of metabolic syndrome (MS) and cardiometabolic risk factors in multiple epidemiology studies. However, whether this association is causal is still unclear. We aimed to test whether genetically lowered vitamin D levels were associated with MS and its metabolic traits, using mendelian randomization (MR) methodology.

Methods

Ten thousand six hundred fifty-five participants were enrolled from the SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. Using four single-nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH) D concentrations, we created a genetic risk score (GRS) as instrumental variable (IV) to estimate the effect of genetically lowered 25(OH) D on MS and cardiometabolic risk factors. MS was defined according to the International Diabetes Federation criteria.

Results

Lower measured 25(OH)D levels were associated with MS (OR 0.921, 95% CI 0.888, 0.954) after multivariable adjustment. However, the MR-derived odds ratio of genetically determined 25(OH) D for risk of MS was 0.977 (95% CI 0.966, 1.030). The MR-derived estimates for raised fasting plasma glucose was 0.578 (95% CI 0.321, 0.980) per 10 nmol/L GRSsynthesis determined increase of 25(OH) D levels.

Conclusions

We found no evidence that genetically determined reduction in 25(OH)D conferred an increased risk of MS and its metabolic traits. However, we created our GRS only on the basis of common variants, which represent limited amount of variance in 25(OH)D. MR studies using rare variants, and large-scale well-designed RCTs about the effect of vitamin D supplementation on MS are warranted to further validate the findings.
Solitary metastasis of myxoid liposarcoma from the thigh to intraperitoneum: a case report
Authors: Kim Dong-Wook , Jee Ye Seob
Published: October 2019

Background

The purpose of case report was to present a rare case of a solitary metastasis of myxoid liposarcoma and discuss the clinical and pathological information for patients treated for metastatic myxoid liposarcoma.

Case presentation

We report our experience with a case of solitary metastasis of myxoid liposarcoma from the thigh to intraperitoneum. The patient was a 60-year-old man who was referred for abdominal discomfort and fatigue. Enhanced computed tomography showed a 25-cm intra-abdominal tumor. He had undergone a wide local excision for a right thigh myxoid liposarcoma 6 years earlier. At laparotomy, a huge multi-lobular cystic mass was identified at the small bowel mesentery. Wide local excision was performed, and the mass was diagnosed as metastatic myxoid liposarcoma. He was discharged without postoperative complications.

Conclusions

We experienced a single intraperitoneal metastasis in a patient with myxoid liposarcoma after radical surgery of the primary site.
Targeting PKCι-PAK1 signaling pathways in EGFR and KRAS mutant adenocarcinoma and lung squamous cell carcinoma
Authors: Ito Masaoki , Codony-Servat Carles , Codony-Servat Jordi , Lligé David , Chaib Imane , Sun Xiaoyan , Miao Jing , Sun Rongwei , Cai Xueting , Verlicchi Alberto , Okada Morihito , Molina-Vila Miguel Angel , Karachaliou Niki , Cao Peng , Rosell Rafael
Published: October 2019

Introduction

p21-activated kinase 1 (PAK1) stimulates growth and metastasis in non-small cell lung cancer (NSCLC). Protein kinase C iota (PKCι) is an enzyme highly expressed in NSCLC, regulating PAK1 signaling. In the present study we explored whether the PKCι-PAK1 signaling pathway approach can be an efficient target in different types of NSCLC cell and mouse models.

Methods

The effect of IPA-3 (PAK1 inhibitor) plus auranofin (PKCι inhibitor) combination was evaluated by cell viability assay, colony formation and western blotting assay, using three types of NSCLC cell lines: EGFR or KRAS mutant adenocarcinoma and squamous cell carcinoma with PAK1 amplification. In addition, for clinical availability, screening for new PAK1 inhibitors was carried out and the compound OTSSP167 was evaluated in combination with auranofin in cell and mice models.

Results

The combination of IPA-3 or OTSSP167 plus auranofin showed high synergism for inhibiting cell viability and colony formation in three cell lines. Mechanistic characterization revealed that this drug combination abrogated expression and activation of membrane receptors and downstream signaling proteins crucial in lung cancer: EGFR, MET, PAK1, PKCι, ERK1/2, AKT, YAP1 and mTOR. A nude mouse xenograft assay demonstrated that this drug combination strongly suppressed tumor volume compared with single drug treatment.

Conclusions

Combination of IPA-3 or OTSSP167 and auranofin was highly synergistic in EGFR or KRAS mutant adenocarcinoma and squamous cell carcinoma cell lines and decreased tumor volume in mice models. It is of interest to further test the targeting of PKCι-PAK1 signaling pathways in EGFR mutant, KRAS mutant and squamous NSCLC patients.
Prevalence and correlates of adherence to movement guidelines among urban and rural children in Mozambique: a cross-sectional study
Authors: Manyanga Taru , Barnes Joel D. , Chaput Jean-Philippe , Katzmarzyk Peter T. , Prista Antonio , Tremblay Mark S.
Published: October 2019

Background

Insufficient physical activity, short sleep duration, and excessive recreational screen time are increasing globally. Currently, there are little to no data describing prevalences and correlates of movement behaviours among children in low-middle-income countries. The few available reports do not include both urban and rural respondents, despite the large proportion of rural populations in low-middle-income countries. We compared the prevalence of meeting 24-h movement guidelines and examined correlates of meeting the guidelines in a sample of urban and rural Mozambican schoolchildren.

Methods

This is cross-sectional study of 9–11 year-old children (n = 683) recruited from 10 urban and 7 rural schools in Mozambique. Moderate- to vigorous-intensity physical activity (MVPA) and sleep duration were measured by waist-worn Actigraph GT3X+ accelerometers. Accelerometers were worn 24 h/day for up to 8 days. Recreational screen time was self-reported. Potential correlates of meeting 24-h movement guidelines were directly measured or obtained from validated items of context-adapted questionnaires. Multilevel multivariable logit models were used to determine the correlates of movement behaviours. Meeting 24-h movement guidelines was defined as ≥60 min/day of MVPA, ≤2 h/day of recreational screen time, and between 9 and 11 h/night of sleep.

Results

More rural (17.7%) than urban (3.6%) children met all three 24-h movement guidelines. Mean MVPA was lower (82.9 ± 29.5 min/day) among urban than rural children (96.7 ± 31.8 min/day). Rural children had longer sleep duration (8.9 ± 0.7 h/night) and shorter recreational screen time (2.7 ± 1.9 h/day) than their urban counterparts (8.7 ± 0.9 h/night and 5.0 ± 2.3 h/day respectively). Parental education (OR: 0.37; CI: 0.16–0.87), school location (OR: 0.21; CI: 0.09–0.52), and outdoor time (OR: 0.67; CI: 0.53–0.85) were significant correlates of meeting all three 24-h movement guidelines.

Conclusions

Prevalence and correlates of meeting movement guidelines differed between urban and rural schoolchildren in Mozambique. On average, both groups had higher daily MVPA minutes, shorter sleep duration, and higher recreational screen time than the 24-h movement guidelines recommend. These findings (e.g., higher than recommended mean daily MVPA minutes) differ from those from high-income countries and highlight the need to sample from both urban and rural areas.
Effects of VEGF blockade on the dynamics of the inflammatory landscape in glioblastoma-bearing mice
Authors: Soubéran Aurélie , Brustlein Sophie , Gouarné Caroline , Chasson Lionel , Tchoghandjian Aurélie , Malissen Marie , Rougon Geneviève
Published: October 2019

Background

Targeting angiogenesis has been and continues to be an attractive therapeutic modality in glioblastoma (GBM) patients. However, GBM rapidly becomes refractory to anti-VEGF therapies. Myeloid cell infiltration is an important determinant of tumor progression. Given that VEGF is a modulator of the innate immune response we sought to analyze the dynamics of this response in a mouse model of GBM undergoing anti-VEGF therapy.

Methods

We grafted GL261-DsRed cells in transgenic Thy1-CFP//LysM-EGFP//CD11c-EYFP reporter mice. We combined recurrent spectral two-photon imaging with multiparametric cytometry, immunostaining, and brain clearing to characterize at two critical stages of tumor development (day 21 and day 28 after tumor grafting) the nature and spatial distribution of the innate response in control and bevacizumab-treated mice.

Results

We report that at an early stage (21 day), VEGF blockade has a detectable effect on the number of microglial cells but only a mild effect on the number of infiltrating myeloid cells. At a later stage (day 28), the treatment resulted in a specific adjustment of dendritic cell subsets. In treated mice, the number of monocytes and their monocyte-derived dendritic cells (moDC) progeny was increased by approximately twofold compared to untreated mice. In agreement, by in vivo quantitative imaging, we observed that treatment increased the number of LysM-EGFP cells traveling in tumor blood vessels and doubled the densities of both infiltrated LysM-EGFP monocytes and double-labeled EGFP/EYFP moDC. The treatment also led to an increased density of conventional cDCs2 subset together with a decrease of cDCs1 subset, necessary for the development of anti-tumor immunity. Finally, we describe differential spatial cell distributions and two immune cell-traveling routes into the brain. LysM-EGFP cells distributed as a gradient from the meninges towards the tumor whereas CD11c-EYFP/MHCII+ cells were located in the basal area of the tumor. Brain clearing also revealed a flow of CD11c-EYFP cells following the corpus callosum.

Conclusion

We uncovered new features in the dynamics of innate immune cells in GBM-bearing mice and deciphered precisely the key populations, i.e., DC subsets controlling immune responses, that are affected by VEGF blockade. Since despite differences, human pathogenesis presents similarities with our mouse model, the data provide new insights into the effect of bevacizumab at the cellular level.