bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of iron status, oxidation response, and DNA methylation profile in response to occupational iron oxide nanoparticles exposure
Authors: Yu Min , Zhou Xingfan , Ju Li , Yu Man , Gao Xiangjing , Zhang Meibian , Tang Shichuan
Published: June 2020

Although the growing development and application of iron oxide nanoparticles (IONPs) may pose exposure risk and adverse health outcomes, biological changes due to occupational exposure remain unexplored. This cross-sectional study recruited 23 workers at a plant that manufactures IONPs and 23 age- and sex-matched controls without metal-rich occupational hazards exposure. Exposure metrics at worksites were monitored, and iron status, oxidation markers, and methylation profiles of genomic DNA in peripheral blood were measured using corresponding enzyme-linked immunosorbent assays and methylation-specific polymerase chain reaction (PCR), respectively. The mass concentration, number counting, and surface area concentration of airborne particles at the worksite significantly increased during the work process of manufacturing/handling IONPs. Overall, compared to controls, workers exhibited increased 5-hydroxymethylcytosine (5hmC) levels without changes in 5-methylcytosine (5mC), hepcidin methylation, iron, soluble transferrin receptor (sTfR), ferritin, hepcidin, 8-hydroxydeoxyguanosine, and glutathione. A positive correlation was found between 5hmC and IONP exposure year with adjustment for age, sex, and cotinine using partial correlation analyses ( r = 0.521, p < 0.001). After stratification of INOPs exposure and 5hmC levels, the univariate general linear model with adjustment for age, sex, and cotinine found that the estimated mean levels of 5mC and sTfR in subjects with low and high 5hmC levels among controls were 11% and 14.4% ( p ≤ 0.01) and 80.9 nM and 70.3 nM ( p < 0.05), respectively. The estimated mean levels of sTfR in workers and controls with low 5hmC levels were 88.3 nM and 68.7 nM ( p ≤ 0.01). Multivariate linear regression analyses suggested an association between sTfR and 5hmC (standardized β = −0.420, p = 0.014) and female sex (standardized β = 0.672, p < 0.001) for subjects with low 5hmC levels. These findings suggest that increased 5hmC could be differentially employed to monitor an epigenetic signature with steady iron homeostasis for occupational IONP-exposed individuals who are likely to experience early but specific decreased sTfR, especially for females concurrent with the onset of increment in 5hmC at low level.
Nanoparticles induced embryo–fetal toxicity
Authors: Wang Zengjin , Wang Zhiping
Published: June 2020

Applications of nanomaterials cause a general concern on their toxicity when they intentionally (such as in medicine) or unintentionally (environment exposure) enter into the human body. As a special subpopulation, pregnant women are more susceptible to nanoparticle (NP)-induced toxicity. More importantly, prenatal exposures may affect the entire life of the fetus. Through blood circulation, NPs may cross placental barriers and enter into fetus. A cascade of events, such as damage in placental barriers, generation of oxidative stress, inflammation, and altered gene expression, may induce delayed or abnormal fetal development. The physicochemical properties of NPs, exposure time, and other factors directly affect nanotoxicity in pregnant populations. Even though results from animal studies cannot directly extrapolate to humans, compelling evidence has already shown that, for pregnant women, caution must be taken when dealing with nanomedicines or NP pollutants.
Micro-drilling of Mg-based MMCs reinforced with SiO2 nanoparticles: An experimental approach
Authors: Sun Fuzhong , Huo Dehong , Fu Guoyu , Teng Xiangyu , Kannan Sathish , Zhang Hao
Published: June 2020

Mg-based metal matrix composites reinforced with nanoparticles are promising biomaterials due to their biocompatibility and high hardness and because they are local and systemic toxicity free. Nano-metal matrix composites are considered to be hard-to-machine materials due to the high strength and high abrasiveness of the reinforcing nanoparticles. In this article, the micro-drilling mechanisms of Mg-based metal matrix composites reinforced with different volume fraction of SiO2 nanoparticles (0.5, 1.0, 1.5, 2.0 vol.%) were investigated experimentally. Results obtained were also compared with pure Mg. First, it was found that the volume fraction and drilling parameters played an important role in the chip formation mechanism. Second, the influence of drilling parameters on hole surface morphology and cutting force were studied, in which both the rotation speed and feedrate affected the surface morphology, and the main factor affecting cutting force was found to be the feedrate. Furthermore, the formation of burrs was investigated. The height of the burr could be reduced by using small feedrate and low rotation speed. Finally, the size effect of micro-drilling was studied. The variation of surface roughness and cutting force of pure Mg and Mg-based metal matrix composites had three changing trends with the uncut chip thickness. The minimum chip thickness of Mg/SiO2 metal matrix composites was determined to be 1.1 μm.
Seventy years after Hench’s Nobel prize: revisiting the use of glucocorticoids in systemic lupus erythematosus
Authors: Ruiz-Irastorza Guillermo , Ugarte Amaia , Ruiz-Arruza Ioana , Khamashta Munther
Published: June 2020

In 1950, Hench, Kendall and Reichstein were awarded with the Nobel Prize in Physiology and Medicine for the isolation and first therapeutic use of glucocorticoids. Since then, they have become one of the main agents in the treatment of systemic lupus erythematosus (SLE). The use of high-dose oral glucocorticoids (usually 1 mg/kg/day of prednisone equivalent) have become the rule for treating moderate to severe lupus activity. In addition, tapering schemes have not been well defined, all this leading to prolonged exposures to potentially damaging amounts of glucocorticoids. Several studies have shown that glucocorticoids are a major cause of toxicity in SLE in a dose-dependent manner, with prolonged doses greater than 7.5 mg/day being associated with damage accrual. Thus, there is an urgent need for different therapeutic schedules that can achieve a rapid and durable control of lupus activity while reducing the many unwanted effects of glucocorticoids. Recent data show that pulses of methyl-prednisolone are an effective first-line therapy to treat lupus flares (not only severe ones) without major short or long-term toxicity and allowing a reduction in oral prednisone doses. Universal use of hydroxychloroquine – always recommended, infrequently accomplished – and early therapy with immunosuppressive drugs also help control SLE and reduce prednisone load. Results from observational studies confirm the more rapid achievement of remission and the reduction of long-term damage using these combination schedules with reduced prednisone doses. Seventy years after their first therapeutic use, we are learning to use glucocorticoids in a more efficient and safe manner.
Antecedents and Impact of E-commerce Adoption among New Venture Firms: Evidence from Tourism and Hospitality Industry
Authors: Mishra Onkar Nath , Gupta Saurabh
Published: June 2020

Newly created ventures face many challenges, of which, successfully competing with rivals is a daunting task. In order to grow, and turn profitable, start-up firms must extensively search for strategies that create and sustain competitive advantage. Adoption of e-commerce is considered as a very potent strategy to beat competitors and generate profits. Taking tourism and hospitality, an information-intensive industry, this study set two primary objectives regarding e-commerce adoption. First, to investigate the antecedents of e-commerce adoption and second, to gather empirical evidences about the impact of e-commerce adoption on such firms. The study was motivated by the paucity of literature on adoption of e-commerce by start-up firms, especially in the tourism and hospitality industry. The empirical results showed that market- and organization-related factors were prime determinants of e-commerce adoption by start-up firms. The study also confirmed the improved performance of tourism and hospitality start-ups as a result of e-commerce adoption.
Research on chaos control of permanent magnet synchronous motor based on the synthetical sliding mode control of inverse system decoupling
Authors: Rongyun Zhang , Changfu Gong , Peicheng Shi , Linfeng Zhao , Changsheng Zheng
Published: June 2020

This article focuses on realizing the chaos control of a permanent magnet synchronous motor by combining a pseudo-linear inverse system of the permanent magnet synchronous motor and synthetical sliding mode control. First, the permanent magnet synchronous motor dimensionless nonlinear mathematical model is established, and its chaos is analyzed by the Lyapunov exponent method. The permanent magnet synchronous motor parameter range when chaos appears is obtained. Then, the inverse system decoupling method is used to analyze the reversibility of the permanent magnet synchronous motor system, and the permanent magnet synchronous motor inverse system is obtained, which is compounded with the original system into a pseudo-linear inverse system that consists of two independent subsystems, including a first-order d-axis current system and a second-order rotational speed system, to decouple the permanent magnet synchronous motor system. Third, the first-order d-axis subsystem is controlled by sliding mode control with a hyperbolic tangent function as the switching function, and the second-order speed subsystem is controlled by super-twisting sliding mode control with a hyperbolic tangent function as the switching function, which is called the synthetical sliding mode control. The permanent magnet synchronous motor pseudo-linear inverse system is controlled by using the synthetical sliding mode to realize the chaos control of the permanent magnet synchronous motor. Finally, three kinds of permanent magnet synchronous motor chaos control systems are established in MATLAB/Simulink software, and the experimental tests are implemented. The results show that the proposed permanent magnet synchronous motor chaos control system has good performance, which can effectively eliminate chattering in sliding mode control and control chaos in the permanent magnet synchronous motor system.
The Transition Value of Business Models for a Sustainable Energy System: The Case of Virtual Peer-to-Peer Energy Communities
Authors: Plewnia Frederik , Guenther Edeltraud
Published: June 2020

Peer-to-peer energy (p2p) communities connect electricity consumers and producers on platforms allowing them to trade energy with each other. By synchronizing local production and consumption, connecting decentral actors, and creating new markets, they can promote a more sustainable energy system. A multicase study and expert interviews were conducted to investigate how the business models of these organizations operate and what value they may provide to stakeholders and the energy system. It was found that, due to current legislation, organizations in Germany mostly facilitate virtual, supraregional p2p energy communities. While these do not offer all the benefits of local p2p energy communities, they do facilitate a range of advantages to stakeholders and the overall energy system. Finally, it is concluded how sustainable business models can offer “system transition value,” driving the dissemination of new technologies, the redesign of markets, and the education of customers to foster a more sustainable energy system.
Deriving a tangible promotional calculus: platform monopolies and political advertising
Authors: Kumar Akshaya
Published: June 2020

This article describes how the monopolistic capitalism of platform economies gets appropriated by political campaigners by highlighting the critical role of derivative valuations in the market without any ‘fundamentals’. I argue that platform economies help generate both the rhetorical flourish and dubious metadata, which provides an unreliable yet vital anchorage towards political campaigns. In this cross-promotional bidding for statistics, the value of these campaigns is staked upon bold claims, affective fluctuations and popularity metrics. This article argues that we must therefore pay attention to the advertorial overlap of interests which makes a particular state form strategically reliant upon the derivative impulse of monopoly capital. It is via the public transcripts of such overlapping tendencies – which make it difficult to distinguish between the product and the advertisement – that derivative valuations emerge, converting intangible assets into tangible gains.
The introduction of new medications in pediatric multiple sclerosis: Open issues and challenges
Authors: Ghezzi Angelo , Amato Maria Pia , Edan Gilles , Hartung Hans-Peter , Havrdová Eva Kubala , Kappos Ludwig , Montalban Xavier , Pozzilli Carlo , Sorensen Per Soelber , Trojano Maria , Vermersch Patrich , Comi Giancarlo
Published: June 2020

Disease-modifying drugs (DMDs) for multiple sclerosis (MS) have been evaluated in pediatric patients in observational studies demonstrating a similar, even better clinical effect compared to adults, with a similar safety. Only fingolimod has been tested in a randomized controlled trial (RCT) and is approved for pediatric multiple sclerosis (ped-MS). Numerous methodological, practical, and ethical issues underline that RCTs are difficult to conduct in ped-MS. This also creates a lack of safety information. To facilitate the availability of new agents in ped-MS, we encourage to develop a different approach based on pharmacokinetic/pharmacodynamic studies to yield information on optimal doses and implementation of obligatory registries to obtain information on safety as primary endpoint.
Postoperative follow-up time and justification in prospective hand surgery research: a systematic review
Authors: Hooper Rachel C. , Nasser Jacob S. , Huetteman Helen E. , Mack Shale J. , Chung Kevin C.
Published: June 2020

We systematically reviewed prospective studies for five hand procedures to analyse postoperative follow-up time, clinical or radiographic plateau, and whether the authors provide justification for times used. Demographic data, outcomes and mean follow-up were analysed. A total of 188 articles met our inclusion criteria. The mean postoperative follow-up time among these studies were carpal tunnel release, 21 months (range 1.5–111); cubital tunnel release, 27 months (2.5–46); open reduction and internal fixation for the distal radius fracture, 24 months (3–120); thumb carpometacarpal joint arthroplasty, 64 months (8.5–228); and flexor tendon repair, 25 months (3–59). Authors provided justification for follow-up intervals in 10% of these reports. We conclude that most prospective clinical studies in hand surgery do not properly justify follow-up length. Clinically unnecessary follow-up is costly without much benefit. In prospective research, we believe justified postoperative follow-up is essential, based on expected time to detect clinical plateau, capture complications and determine the need for secondary surgery.

Level of evidence: III
Conservative treatment of refractures after modified tension band wiring of fifth metatarsal base stress fractures in athletes
Authors: Lee Kyung Tai , Kim Ki Chun , Young Ki Won , Jegal Hyuk , Park Young Uk , Lee Hong Seop , Roh Youngju
Published: June 2020

Objective:

Recurrent fifth metatarsal base stress fractures (MT5-BSF) in athletes present a challenging problem. The aim of this study was to evaluate the result of conservative treatment for the refracture of MT5-BSF after modified tension band wiring (MTBW).

Materials and Methods:

The outcomes of 15 elite athletes undergoing conservative treatment for refracture of MT5-BSF after MTBW were retrospectively reviewed. They were instructed to avoid weight-bearing with short leg cast for 6 weeks. After that, they started partial weight with a postop shoe. Stepwise exercise followed bone union by radiographs.

Results:

Thirteen cases (86.6%) had a complete bone union after a mean of 18.9 ± 8.6 weeks. Twelve cases (80%) returned to their previous activity level and maintained for at least two consecutive seasons.

Conclusion:

Eighty percent of all athletic patients with the conservative treatment for refractures with healed MT5-BSF after MTBW on the plantar-lateral side could maintain and return to their previous sports activity for at least 2 years.
Lysine acetyltransferase Tip60 is required for hematopoietic stem cell maintenance
Authors: Numata Akihiko , Kwok Hui Si , Zhou Qi-Ling , Li Jia , Tirado-Magallanes Roberto , Angarica Vladimir Espinosa , Hannah Rebecca , Park Jihye , Wang Chelsia Qiuxia , Krishnan Vaidehi , Rajagopalan Deepa , Zhang Yanzhou , Zhou Siqin , Welner Robert S. , Osato Motomi , Jha Sudhakar , Bohlander Stefan K. , Göttgens Berthold , Yang Henry , Benoukraf Touati , Lough John W. , Bararia Deepak , Tenen Daniel G.
Published: June 2020

Hematopoietic stem cells (HSCs) have the potential to replenish the blood system for the lifetime of the organism. Their 2 defining properties, self-renewal and differentiation, are tightly regulated by the epigenetic machineries. Using conditional gene-knockout models, we demonstrated a critical requirement of lysine acetyltransferase 5 (Kat5, also known as Tip60) for murine HSC maintenance in both the embryonic and adult stages, which depends on its acetyltransferase activity. Genome-wide chromatin and transcriptome profiling in murine hematopoietic stem and progenitor cells revealed that Tip60 colocalizes with c-Myc and that Tip60 deletion suppress the expression of Myc target genes, which are associated with critical biological processes for HSC maintenance, cell cycling, and DNA repair. Notably, acetylated H2A.Z (acH2A.Z) was enriched at the Tip60-bound active chromatin, and Tip60 deletion induced a robust reduction in the acH2A.Z/H2A.Z ratio. These results uncover a critical epigenetic regulatory layer for HSC maintenance, at least in part through Tip60-dependent H2A.Z acetylation to activate Myc target genes.
Glucagon-like peptide 2 for intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans
Authors: Norona Johana , Apostolova Petya , Schmidt Dominik , Ihlemann Rebekka , Reischmann Nadine , Taylor Gregory , Köhler Natalie , de Heer Jocelyn , Heeg Steffen , Andrieux Geoffroy , Siranosian Benjamin A. , Schmitt-Graeff Annette , Pfeifer Dietmar , Catalano Antonella , Frew Ian J. , Proietti Michele , Grimbacher Bodo , Bulashevska Alla , Bhatt Ami S. , Brummer Tilman , Clauditz Till , Zabelina Tatjana , Kroeger Nicolaus , Blazar Bruce R. , Boerries Melanie , Ayuk Francis , Zeiser Robert
Published: June 2020

Acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). Although currently used GVHD treatment regimens target the donor immune system, we explored here an approach that aims at protecting and regenerating Paneth cells (PCs) and intestinal stem cells (ISCs). Glucagon-like-peptide-2 (GLP-2) is an enteroendocrine tissue hormone produced by intestinal L cells. We observed that acute GVHD reduced intestinal GLP-2 levels in mice and patients developing GVHD. Treatment with the GLP-2 agonist, teduglutide, reduced de novo acute GVHD and steroid-refractory GVHD, without compromising graft-versus-leukemia (GVL) effects in multiple mouse models. Mechanistically GLP-2 substitution promoted regeneration of PCs and ISCs, which enhanced production of antimicrobial peptides and caused microbiome changes. GLP-2 expanded intestinal organoids and reduced expression of apoptosis-related genes. Low numbers of L cells in intestinal biopsies and high serum levels of GLP-2 were associated with a higher incidence of nonrelapse mortality in patients undergoing allo-HCT. Our findings indicate that L cells are a target of GVHD and that GLP-2–based treatment of acute GVHD restores intestinal homeostasis via an increase of ISCs and PCs without impairing GVL effects. Teduglutide could become a novel combination partner for immunosuppressive GVHD therapy to be tested in clinical trials.
The microbiome of diabetic foot ulcers: a comparison of swab and tissue biopsy wound sampling techniques using 16S rRNA gene sequencing
Authors: Travis J. , Malone M. , Hu H. , Baten A. , Johani K. , Huygens F. , Vickery K. , Benkendorff K.
Published: June 2020

Background

Health-care professionals need to collect wound samples to identify potential pathogens that contribute to wound infection. Obtaining appropriate samples from diabetic foot ulcers (DFUs) where there is a suspicion of infection is of high importance. Paired swabs and tissue biopsies were collected from DFUs and both sampling techniques were compared using 16S rRNA gene sequencing.

Results

Mean bacterial abundance determined using quantitative polymerase chain reaction (qPCR) was significantly lower in tissue biopsies (p = 0.03). The mean number of reads across all samples was significantly higher in wound swabs $$ \Big(\overline{X} $$(X¯ = 32,014) compared to tissue ($$ \overline{X} $$X¯ = 15,256, p = 0.001). Tissue biopsies exhibited greater overall diversity of bacteria relative to swabs (Shannon’s H diversity p = 0.009). However, based on a presence/absence analysis of all paired samples, the frequency of occurrence of bacteria from genera of known and potential pathogens was generally higher in wound swabs than tissue biopsies. Multivariate analysis identified significantly different bacterial communities in swabs compared to tissue (p = 0.001). There was minimal correlation between paired wound swabs and tissue biopsies in the number and types of microorganisms. RELATE analysis revealed low concordance between paired DFU swab and tissue biopsy samples (Rho = 0.043, p = 0.34).

Conclusions

Using 16S rRNA gene sequencing this study identifies the potential for using less invasive swabs to recover high relative abundances of known and potential pathogen genera from DFUs when compared to the gold standard collection method of tissue biopsy.
The differential expression patterns of paralogs in response to stresses indicate expression and sequence divergences
Authors: Lian Shuaibin , Zhou Yongjie , Liu Zixiao , Gong Andong , Cheng Lin
Published: June 2020

Background

Theoretically, paralogous genes generated through whole genome duplications should share identical expression levels due to their identical sequences and chromatin environments. However, functional divergences and expression differences have arisen due to selective pressures throughout evolution. A comprehensive investigation of the expression patterns of paralogous gene pairs in response to various stresses and a study of correlations between the expression levels and sequence divergences of the paralogs are needed.

Results

In this study, we analyzed the expression patterns of paralogous genes under different types of stress and investigated the correlations between the expression levels and sequence divergences of the paralogs. We analyzed the differential expression patterns of the paralogs under four different types of stress (drought, cold, infection, and herbivory) and classified them into three main types according to their expression patterns. We then further analyzed the differential expression patterns under various degrees of stress and constructed corresponding co-expression networks of differentially expressed paralogs and transcription factors. Finally, we investigated the correlations between the expression levels and sequence divergences of the paralogs and identified positive correlations between expression level and sequence divergence. With regard to sequence divergence, we identified correlations between selective pressures and phylogenetic relationships.

Conclusions

These results shed light on differential expression patterns of paralogs in response to environmental stresses and are helpful for understanding the relationships between expression levels and sequences divergences.
The relationship of lipoprotein-associated phospholipase A2 activity with the seriousness of coronary artery disease
Authors: Zhang Hao , Gao Yang , Wu Dan , Zhang Dingguo
Published: June 2020

Background

The level of lipoprotein-associated phospholipase A2 (LP-PLA2) in serum is independently correlated to coronary artery diseases (CAD). The aim of the study was to determine whether LP-PLA2 activity is positively associated with the seriousness of CAD.

Methods

Amount to 1056 patients suspected of having CAD underwent coronary angiography (CAG) to determine the seriousness of CAD. According to the amount of diseased coronary branches, the 1056 patients were split into three groups: single-vessel stenosis group, multiple-vessels stenosis group (> or = 2 diseased coronary branches),and control group (no diseased coronary branches). According to CAG results, electrocardiography, cardiac biomarker, and clinical presentation, all patients were split into four groups: acute myocardial infarction (AMI), unstable angina (UA), stable angina (SA), and control groups (excluding CAD). The activity of LP-PLA2 was compared statistically among the subgroups. Receiver operating characteristic analysis was applied to investigate the role of LP-PLA2 in evaluating the presence and seriousness of CAD.

Results

The level of LP-PLA2 increased in line with the number of diseased coronary branches. The levels of LP-PLA2 in the AMI and UA groups were observably higher when compared with the control and SA groups. LP-PLA2 had 75.6% sensitivity and 67.3% specificity for recognizing CAD, and 53.0% sensitivity and 80.3% specificity for recognizing severe coronary artery lesions.

Conclusion

The activity of LP-PLA2 is positively correlated to the seriousness of CAD.
Short-course antibiotic regimen compared to conventional antibiotic treatment for gram-positive cocci infective endocarditis: randomized clinical trial (SATIE)
Authors: Olmos Carmen , Vilacosta Isidre , López Javier , Sáez Carmen , Anguita Manuel , García-Granja Pablo Elpidio , Sarriá Cristina , Silva Jacobo , Álvarez-Álvarez Belén , Martínez-Monzonis María Amparo , Castillo Juan Carlos , Seijas José , López-Picado Amanda , Peral Vicente , Maroto Luis , San Román J. Alberto
Published: June 2020

Background

Most serious complications of infective endocarditis (IE) appear in the so-called “critical phase” of the disease, which represents the first days after diagnosis. The majority of patients overcoming the acute phase has a favorable outcome, yet they remain hospitalized for a long period of time mainly to complete antibiotic therapy. The major hypothesis of this trial is that in patients with clinically stable IE and adequate response to antibiotic treatment, without signs of persistent infection, periannular complications or metastatic foci, a shorter antibiotic time period would be as efficient and safe as the classic 4 to 6 weeks antibiotic regimen.

Methods

Multicenter, prospective, randomized, controlled open-label, phase IV clinical trial with a non-inferiority design to evaluate the efficacy of a short course (2 weeks) of parenteral antibiotic therapy compared with conventional antibiotic therapy (4–6 weeks).

Sample: patients with IE caused by gram-positive cocci, having received at least 10 days of conventional antibiotic treatment, and at least 7 days after surgery when indicated, without clinical, analytical, microbiological or echocardiographic signs of persistent infection. Estimated sample size: 298 patients. Intervention: Control group: standard duration antibiotic therapy, (4 to 6 weeks) according to ESC guidelines recommendations. Experimental group: short-course antibiotic therapy for 2 weeks. The incidence of the primary composite endpoint of all-cause mortality, unplanned cardiac surgery, symptomatic embolisms and relapses within 6 months after the inclusion in the study will be prospectively registered and compared.

Conclusions

SATIE will investigate whether a two weeks short-course of intravenous antibiotics in patients with IE caused by gram-positive cocci, without signs of persistent infection, is not inferior in safety and efficacy to conventional antibiotic treatment (4–6 weeks).

Trial registration

ClinicalTrials.gov Identifier: NCT04222257 (January 7, 2020).

EudraCT 2019–003358-10.
Human adenovirus Coinfection aggravates the severity of Mycoplasma pneumoniae pneumonia in children
Authors: Gao Jiaojiao , Xu Lili , Xu Baoping , Xie Zhengde , Shen Kunling
Published: June 2020

Background

Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen of community-acquired pneumonia (CAP) in children. The coinfection rate of M. pneumoniae pneumonia (MPP) can reach 52% in some areas, but the effects of coinfection with different pathogens have not been clearly recognized.

Methods

The cases of MPP hospitalized in Beijing Children’s Hospital from 1/1/2014 to 12/31/2016 were screened. MPP patients coinfected with Human adenovirus (HAdV) were categorized into the research group. Patients with single M. pneumoniae infection were categorized into the control group, matching the research group by age and admission time with a ratio of 1:3. Clinical manifestations, laboratory examinations, and disease severity were compared between these two groups.

Results

A total of 2540 hospitalized MPP cases were screened in Beijing Children’s Hospital, among which thirty cases were enrolled in the research group and ninety cases were enrolled in the control group. The results indicated that patients in the research group had longer hospital stays, longer fever durations and a higher rate of dyspnea, as well as a larger proportion applications of oxygen therapy and noninvasive continuous positive airway pressure (NCPAP). No obvious differences were found in lab examinations within the two groups. Regarding disease severity, the proportions of extremely severe pneumonia and severe disease defined by the clinical score system were higher in the research group than in the control group.

Conclusion

Compared with single M. pneumoniae infection, MPP coinfected with HAdV in children was relatively more serious.
Failure to thrive - an overlooked manifestation of KMT2B-related dystonia: a case presentation
Authors: Ng Andrew , Galosi Serena , Salz Lisa , Wong Terence , Schwager Caitlin , Amudhavalli Shivarajan , Gelineau-Morel Rose , Chowdhury Shimul ,   on behalf of Rady Children’s Institute for Genomic Medicine Investigators, Friedman Jennifer
Published: June 2020

Background

KMT2B-related dystonia is a recently described form of childhood onset dystonia that may improve with deep brain stimulation. Prior reports have focused on neurologic features including prominent bulbar involvement without detailing general health consequences that may result from orolingual dysfunction. We describe a family with novel KMT2B mutation with several members with failure to thrive to highlight this non-neurologic, but consequential impact of mutation in this gene.

Case presentation

We present a case of a 15-year old female who was admitted and evaluated for failure to thrive. On exam, she had severe speech dysfluency, limited ability to protrude the tongue, and generalized dystonia involving the oromandibular region, right upper and left lower extremity with left foot inversion contracture. The proband and her parents underwent whole genome sequencing. A previously undescribed variant, c.4960 T > C (p.Cys1654Arg), was identified in the KMT2B gene in the proband and mother, and this variant was subsequently confirmed in two maternal cousins, one with failure to thrive. Literature review identified frequent reports of prominent bulbar involvement but failure to thrive is rarely mentioned.

Conclusion

Failure to thrive is a common pediatric clinical condition that has consequences for growth and development. In the presence of an abnormal neurologic exam, a search for a specific underlying genetic etiology should be pursued. With this case series, we highlight an unusual potentially treatable cause of failure to thrive, reinforce the importance of precise molecular diagnosis for patients with failure to thrive and an abnormal neurologic exam, and underscore the importance of cascade screening of family members.
Increased risk of tinnitus in patients with early-onset cataracts: a nationwide population-based case-control study
Authors: Hsieh Yi-Ching , Chang Cheng-Hsien , Tsai Yi-Yu , Lin Cheng-Li , Ng Telk-Ying , Chiang Chun-Chi
Published: June 2020

Background

This study aimed to investigate the association between early-onset cataract and tinnitus using a population-based database.

Methods

Retrospective claims data from the Taiwan National Health Insurance Research Database were analysed. Study subjects comprised patients with early-onset cataract, aged 20–55 years and diagnosed between 2000 and 2010 (n = 2084) and a comparison cohort without the disease (n = 8336). Both cohorts were followed until 2010 to estimate the incidence of tinnitus. To calculate the risk of tinnitus in the case and control groups, Cox proportional hazards models were used and presented as hazard ratios (HRs), adjusted HRs (aHRs) and 95% confidence intervals (CIs).

Results

Patients with early-onset cataract had 1.53-fold increased risk (HR = 1.53, 95% CI = 1.17–2.01,p < 0.01) of developing tinnitus than controls. The number of patients with vertigo (p < 0.0001), insomnia (p < 0.0001), anxiety (p < 0.0001) and hearing loss (p < 0.0001) as comorbidities was also significantly higher in the case group. After adjusting for age, sex and all listed comorbidities, patients with increasing age (aHR = 1.04, 95% CI = 1.02–1.07), early-onset cataract (aHR = 1.32, 95% CI = 1.01–1.74), vertigo (aHR = 1.75, 95% CI = 1.15–2.67), insomnia (aHR = 1.48, 95% CI = 1.14–1.93) and hearing loss (aHR = 6.20, 95% CI = 3.58–10.70) had significantly higher risk of tinnitus.

Conclusions

Patients with early-onset cataract are at an increased risk of developing tinnitus in subsequent years and should receive further evaluation for early diagnosis and management if any signs of tinnitus occur.
The Binge Eating Genetics Initiative (BEGIN): study protocol
Authors: Bulik Cynthia M. , Butner Jonathan E. , Tregarthen Jenna , Thornton Laura M. , Flatt Rachael E. , Smith Tosha , Carroll Ian M. , Baucom Brian R.W. , Deboeck Pascal R.
Published: June 2020

Background

The Binge Eating Genetics Initiative (BEGIN) is a multipronged investigation examining the interplay of genomic, gut microbiota, and behavioral factors in bulimia nervosa and binge-eating disorder.

Methods

1000 individuals who meet current diagnostic criteria for bulimia nervosa or binge-eating disorder are being recruited to collect saliva samples for genotyping, fecal sampling for microbiota characterization, and recording of 30 days of passive data and behavioral phenotyping related to eating disorders using the appRecovery Recordadapted for the Apple Watch.

Discussion

BEGIN examines the interplay of genomic, gut microbiota, and behavioral factors to explore etiology and develop predictors of risk, course of illness, and response to treatment in bulimia nervosa and binge-eating disorder. We will optimize the richness and longitudinal structure of deep passive and active phenotypic data to lay the foundation for a personalized precision medicine approach enabling just-in-time interventions that will allow individuals to disrupt eating disorder behaviors in real time before they occur.

Trial registration

The ClinicalTrials.gov identifier isNCT04162574. November 14, 2019, Retrospectively Registered.
Antidepressants and movement disorders: a postmarketing study in the world pharmacovigilance database
Authors: Revet Alexis , Montastruc François , Roussin Anne , Raynaud Jean-Philippe , Lapeyre-Mestre Maryse , Nguyen Thi Thu Ha
Published: June 2020

Background

Antidepressants-induced movement disorders are rare and imperfectly known adverse drug reactions. The risk may differ between different antidepressants and antidepressants’ classes. The objective of this study was to assess the putative association of each antidepressant and antidepressants’ classes with movement disorders.

Methods

Using VigiBase®, the WHO Pharmacovigilance database, disproportionality of movement disorders’ reporting was assessed among adverse drug reactions related to any antidepressant, from January 1967 to February 2017, through a case/non-case design. The association between nine subtypes of movement disorders (akathisia, bruxism, dystonia, myoclonus, parkinsonism, restless legs syndrome, tardive dyskinesia, tics, tremor) and antidepressants was estimated through the calculation first of crude Reporting Odds Ratio (ROR), then adjusted ROR on four potential confounding factors: age, sex, drugs described as able to induce movement disorders, and drugs used to treat movement disorders.

Results

Out of the 14,270,446 reports included in VigiBase®, 1,027,405 (7.2%) contained at least one antidepressant, among whom 29,253 (2.8%) reported movement disorders. The female/male sex ratio was 2.15 and the mean age 50.9 ± 18.0 years. We found a significant increased ROR for antidepressants in general for all subtypes of movement disorders, with the highest association with bruxism (ROR 10.37, 95% CI 9.62–11.17) and the lowest with tics (ROR 1.49, 95% CI 1.38–1.60). When comparing each of the classes of antidepressants with the others, a significant association was observed for all subtypes of movement disorders except restless legs syndrome with serotonin reuptake inhibitors (SRIs) only. Among antidepressants, mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan and fluvoxamine were associated with the highest level to movement disorders and citalopram, paroxetine, duloxetine and mirtazapine were the most frequently associated with movement disorders. An association was also found with eight other antidepressants.

Conclusions

A potential harmful association was found between movement disorders and use of the antidepressants mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan, fluvoxamine, citalopram, paroxetine, duloxetine, bupropion, clomipramine, escitalopram, fluoxetine, mianserin, sertraline, venlafaxine and vilazodone. Clinicians should beware of these adverse effects and monitor early warning signs carefully. However, this observational study must be interpreted as an exploratory analysis, and these results should be refined by future epidemiological studies.
Using mind control to modify cue-reactivity in AUD: the impact of mindfulness-based relapse prevention on real-time fMRI neurofeedback to modify cue-reactivity in alcohol use disorder: a randomized controlled trial
Authors: Weiss Franziska , Aslan Acelya , Zhang Jingying , Gerchen Martin Fungisai , Kiefer Falk , Kirsch Peter
Published: June 2020

Background

Alcohol Use Disorder is a severe mental disorder affecting the individuals concerned, their family and friends and society as a whole. Despite its high prevalence, novel treatment options remain rather limited. Two innovative interventions used for treating severe disorders are the use of real-time functional magnetic resonance imaging neurofeedback that targets brain regions related to the disorder, and mindfulness-based treatments. In the context of the TRR SFB 265 C04 “Mindfulness-based relapse prevention as an addition to rtfMRI NFB intervention for patients with Alcohol Use Disorder (MiND)” study, both interventions will be combined to a state-of-the art intervention that will use mindfulness-based relapse prevention to improve the efficacy of a real-time neurofeedback intervention targeting the ventral striatum, which is a brain region centrally involved in cue-reactivity to alcohol-related stimuli.

Methods/design

After inclusion, N = 88 patients will be randomly assigned to one of four groups. Two of those groups will receive mindfulness-based relapse prevention. All groups will receive two fMRI sessions and three real-time neurofeedback sessions in a double-blind manner and will regulate either the ventral striatum or the auditory cortex as a control region. Two groups will additionally receive five sessions of mindfulness-based relapse prevention prior to the neurofeedback intervention. After the last fMRI session, the participants will be followed-up monthly for a period of 3 months for an assessment of the relapse rate and clinical effects of the intervention.

Discussion

The results of this study will give further insights into the efficacy of real-time functional magnetic resonance imaging neurofeedback interventions for the treatment of Alcohol Use Disorder. Additionally, the study will provide further insight on neurobiological changes in the brain caused by the neurofeedback intervention as well as by the mindfulness-based relapse prevention. The outcome might be useful to develop new treatment approaches targeting mechanisms of Alcohol Use Disorder with the goal to reduce relapse rates after discharge from the hospital.

Trial registration

This trial is pre-registered at clinicaltrials.gov (trial identifier: NCT04366505; WHO Universal Trial Number (UTN): U1111–1250-2964). Registered 30 March 2020, published 29 April 2020.
Adolescents at risk of self-harm in Ghana: a qualitative interview study exploring the views and experiences of key adult informants
Authors: Quarshie Emmanuel N-B. , Waterman Mitch G. , House Allan O.
Published: June 2020

Background

In Ghana, rates of self-harm in young people are as high as they are in high income countries. Self-reported interpersonal, familial and societal stressors form the most important background, and self-harm is seen by young people as a way of responding to that stress. In the present study, we obtained the views of key adult informants about self-harm among adolescents in Ghana – what they thought as possible reasons for self-harm in young people and what actions might be needed at an individual or population level to respond to the problem.

Methods

We interviewed face-to-face 11 adults, using a semi-structured interview guide. We used an experiential thematic analysis technique to analyse the transcribed interviews.

Results

The analysis identified five themes: “underestimating the prevalence of self-harm in adolescents”, “life on the streets makes self-harm less likely”, “self-harm in adolescents is socially and psychologically understandable”, “ambivalence about responding to adolescent self-harm”, and “few immediate opportunities for self-harm prevention in Ghana”. Adolescent self-harm was acknowledged but its scale was underestimated. The participants offered explanations for adolescent self-harm in social and psychological terms that are recognisable from accounts in high income countries. Low rates among street-connected young people were explained by their overarching orientation for survival. Participants agreed that identification was important, but they expressed a sense of inadequacy in identifying and supporting adolescents at risk of self-harm. Again, the participants agreed that self-harm in adolescents should be prevented, but they recognised that relevant policies were not in place or if there were policies they were not implemented – mental health and self-harm were not high on public or political priorities.

Conclusions

The adults we interviewed about young people who self-harm see themselves as having a role in identifying adolescents at risk of self-harm and see the organisations in which they work as having a role in responding to individual young people in need. These are encouraging findings that point to at least one strand of a policy in Ghana for addressing the problem of self-harm in young people.
Patient and healthcare provider experiences of hepatitis C treatment with direct-acting antivirals in Rwanda: a qualitative exploration of barriers and facilitators
Authors: Serumondo Janvier , Penkunas Michael J. , Niyikora Julienne , Ngwije Alida , Kiromera Athanase , Musabeyezu Emmanuel , Umutesi Justine , Umuraza Sabine , Musengimana Gentille , Nsanzimana Sabin
Published: June 2020

Background

Direct-acting antivirals (DAAs) are increasingly accessible to patients with hepatitis C (HCV) worldwide and are being introduced through national health systems in sub-Saharan Africa. DAAs are highly efficacious when tested in controlled trials, yet patients treated outside of study settings often encounter challenges in completing the full treatment and follow-up sequence. Little information is available on the influences of successful DAA implementation in sub-Saharan Africa. This qualitative study explored the individual- and system-level barriers and enablers of DAA treatment in Rwanda between March 2015 and November 2017.

Methods

Face-to-face interviews were conducted with 39 patients who initiated care at one of four referral hospitals initially offering DAAs. Ten healthcare providers who managed HCV treatment participated in face-to-face interviews to examine system-level barriers and facilitators. Interview data were analyzed using a general inductive approach in alignment with the a priori objective of identifying barriers and facilitators of HCV care.

Results

Barriers to successful treatment included patients’ lack of knowledge surrounding HCV and its treatment; financial burdens associated with paying for medication, laboratory testing, and transportation; the cumbersome nature of the care pathway; the relative inaccessibility of diagnostics technology; and heavy workloads of healthcare providers accompanied by a need for additional HCV-specific training. Patients and healthcare providers were highly aligned on individual- and system-level barriers to care. The positive patient-provider relationship, strong support from community and family members, lack of stigma, and mild side effect profile of DAAs all positively influenced patients’ engagement in treatment.

Conclusions

Several interrelated factors acted as barriers and facilitators to DAA treatment in Rwanda. Patients’ and healthcare providers’ perceptions were in agreement, suggesting that the impeding and enabling factors were well understood by both groups. These results can be used to enact evidence-informed interventions to help maximize the impact of DAAs as Rwanda moves towards HCV elimination.