bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression profiling and analysis of some miRNAs in subcutaneous white adipose tissue during development of obesity
Authors: Youssef Elham M. , Elfiky Asmaa M. , BanglySoliman  , Abu-Shahba Nourhan , Elhefnawi Mahmoud M.
Published: May 2020

Background

MicroRNAs are emerging as new mediators in the regulation of adipocyte physiology and have been approved to play a role in obesity. Despite several studies have focused on microRNA expression profiles and functions in different metabolic tissues, little is known about their response to nutritional interventions in white adipose tissue during obesity stages, and whether they differ in this response to weight-reduction strategy is poorly understood. Our objectives were to study the dysregulation of some miRNAs in subcutaneous inguinal white adipose tissue during weight change, expansion/reduction; in response to both a high-fat diet and switching to a normal diet feeding, and to evaluate them as potential biomarkers and therapeutic targets for early obesity management

Method

A hundred 6-week-old male Wister rats were randomly divided into a normal diet group (N.D), a high-fat diet group (H.F.D), and a switched to a normal diet group (H.F.D/N.D). At the beginning and at intervals 2 weeks, serum lipid, hormone levels, total body fat mass, and inguinal subcutaneous white adipose tissue mass (WAT) measurements were recorded using dual-energy X-ray absorptiometry (DEXA). The expression levels of microRNAs were evaluated using real-time PCR.

Results

Significant alterations were observed in serum glucose, lipid profile, and adipokine hormones during the early stages of obesity development. Alteration in rno-mir 30a-5p, rno-mir 133a-5p, and rno-mir 107-5p expression levels were observed at more than one time point. While rno-let-7a-5p, rno-mir 193a-5p, and rno-mir125a-5p were downregulated and rno-mir130a-5p was upregulated at all time points within 2 to 4 weeks in response to H.F.D feeding for 10 weeks. The impact of switching to normal diet has a reversed effect on lipid profile, adipokine hormone levels, and some miRNAs. The bioinformatics results have identified a novel and important pathway related to inflammatory signalling.

Conclusion

Our research demonstrated significant alterations in some adipocyte-expressed miRNAs after a short time of high caloric diet consumption. This provides further evidence of the significant role of nutrition as an epigenetic factor in regulation of lipid and glucose metabolism genes by modulating of related key miRNAs. Therefore, we suggest that miRNAs could be used as biomarkers for adiposity during diet-induced obesity. Perhaps limitation in calories intake is a way to manipulate obesity and associated metabolic disorders. Further studies are needed to fully elucidate the role of microRNAs in the development of obesity
Transfer posterior error probability estimation for peptide identification
Authors: Yi Xinpei , Gong Fuzhou , Fu Yan
Published: May 2020

Background

In shotgun proteomics, database searching of tandem mass spectra results in a great number of peptide-spectrum matches (PSMs), many of which are false positives. Quality control of PSMs is a multiple hypothesis testing problem, and the false discovery rate (FDR) or the posterior error probability (PEP) is the commonly used statistical confidence measure. PEP, also called local FDR, can evaluate the confidence of individual PSMs and thus is more desirable than FDR, which evaluates the global confidence of a collection of PSMs. Estimation of PEP can be achieved by decomposing the null and alternative distributions of PSM scores as long as the given data is sufficient. However, in many proteomic studies, only a group (subset) of PSMs, e.g. those with specific post-translational modifications, are of interest. The group can be very small, making the direct PEP estimation by the group data inaccurate, especially for the high-score area where the score threshold is taken. Using the whole set of PSMs to estimate the group PEP is inappropriate either, because the null and/or alternative distributions of the group can be very different from those of combined scores.

Results

The transfer PEP algorithm is proposed to more accurately estimate the PEPs of peptide identifications in small groups. Transfer PEP derives the group null distribution through its empirical relationship with the combined null distribution, and estimates the group alternative distribution, as well as the null proportion, using an iterative semi-parametric method. Validated on both simulated data and real proteomic data, transfer PEP showed remarkably higher accuracy than the direct combined and separate PEP estimation methods.

Conclusions

We presented a novel approach to group PEP estimation for small groups and implemented it for the peptide identification problem in proteomics. The methodology of the approach is in principle applicable to the small-group PEP estimation problems in other fields.
Impact of Erythropoietin in the management of Hypoxic Ischaemic Encephalopathy in resource-constrained settings: protocol for a randomized control trial
Authors: Ezenwa Beatrice , Ezeaka Chinyere , Fajolu Iretiola , Ogbenna Anne , Olowoyeye Omodele , Nwaiwu Obiyo , Opoola Zainab , Olorunfemi Gbenga
Published: May 2020

Background

Perinatal asphyxia, more appropriately known as hypoxic-ischemic encephalopathy (HIE), is a condition characterized by clinical and laboratory evidence of acute or sub-acute brain injury resulting from systemic hypoxemia and/or reduced cerebral blood flow. HIE is a common and devastating clinical condition in resource-poor countries with poor treatment outcome. This paper describes the protocol for an ongoing study that aims to evaluate the neuroprotective effects of Erythropoietin (EPO) as compared to routine care in the management of moderate to severe HIE among term infants.

Methods

This study is a double-blind randomized controlled trial that will be conducted in the neonatal wards of the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria, over a two-year period after ethical approvals and consents. One hundred and twenty-eight term newborns (≥ 37 weeks gestation) diagnosed with moderate/ severe HIE at admission will be allocated by randomization to receive either EPO or normal saline. All the participants will be offered standard care according to the unit protocol for HIE. Baseline investigations and close monitoring of the babies are done until discharge. Participants are followed up for 2 years to monitor their outcome (death or neurological development) using standard instruments.

Discussion

Previous trials had shown that EPO confers neuroprotective benefits and improve neurological and behavioral outcome in infants with HIE both singly or as an adjuvant to therapeutic hypothermia. This study hypothesized that administering EPO to newborns with moderate /severe HIE can positively influence their clinical and neurological outcomes and will provide evidence to either support or disprove the usefulness of Erythropoietin as a sole agent in the treatment of HIE, especially in resource-limited environment with the highest burden of the disease.

Trial registration

The study has been registered with the Pan African Clinical trials registry on the 2nd of December 2018, with registration number PACTR201812814507775.
Does the McRoberts’ manoeuvre need to start with thigh abduction? An innovative biomechanical study
Authors: Desseauve David , Fradet Laetitia , Gherman Robert B. , Cherni Yosra , Gachon Bertrand , Pierre Fabrice
Published: May 2020

Background

Guidelines and description about the achievement of the McRoberts manoeuvre are discordant, particularly concerning the need for abduction before the beginning of the manoeuvre. We sought to compare the biomechanical efficiency of the McRoberts’ manoeuvre, with and without thigh abduction.

Methods

In a postural comparative study, twenty-three gravidas > 32 weeks of gestational age and not in labour were assessed during three repetitions of two McRoberts’ manoeuvre that differed in terms of starting position. For the (i) McRoberts, the legs were initially placed in stirrups; for the (m) McRoberts, the legs were resting on the bed, with thighs in wide abduction. For each manoeuvre, flexion of the plane of the external conjugate of the pelvis on the spine (ANGce), hip flexion and abduction, were assessed using an optoelectronic motion capture system. Lumbar curve were assessed with Epionics Spine® system. Temporal parameters including movement duration or acceleration of the external conjugate were also computed. All values ​​obtained for the two types of manoeuvres were compared using a Wilcoxon matched-pairs signed-ranks test. The significance level was defined as p < 0.05.

Results

The starting position of McRoberts’ otherwise had no effect on the maximum ANGce (p = 0.199), the minimal lordosis of the lumbar curve (p = 0.474), or the maximal hip flexion (p = 0.057). The other parameters were not statistically different according to the starting position (p > 0.005).

Conclusion

Regardless of the starting position, the McRoberts’ manoeuvre allows ascension of the pubic symphysis and reduction of the lumbar lordosis. This results imply that the McRoberts’ manoeuvre could be performed with the legs initially placed in the stirrups.
Correction to: Indirect choroidal neovascularization secondary to a posterior-segment intraocular foreign body – case report
Authors: Lin Yu-Shiuan , Peng Kai-Ling
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Inequalities in health care utilization for common illnesses among under five children in Bangladesh
Authors: khanam Moriam , Hasan Emran
Published: May 2020

Background

Reducing child mortality and morbidity is a public health concern globally. Like many other developing countries, Bangladesh is struggling to improve child health status as the use of medical treatment is still not at a satisfactory level. Hence, the objective of this study is to identify the contributing factors for inequalities in the use of medical treatment for common childhood illnesses in Bangladesh.

Methods

The study used data from the latest Bangladesh Demographic and Health Survey (BDHS)-2014. Children who had diarrhea, fever and cough in the 2 weeks preceding the survey were included in this study. Bivariate and multivariate analyses were conducted to unearth the influential factors for medical treatment use among under-five children with childhood illnesses. In the multivariate logistic regression, adjusted odds ratios with p values less than 0.05 were considered for determining significant predictors.

Results

This study found that only 37% of children suffering from fever/cough sought medical treatment while this figure was approximately 36% for diarrhea. Age of children, household wealth status, father’s education level, region of residence, number of children in the household, access to electronic media were identified as factors contributing to inequality in health care utilization for common childhood illnesses in Bangladesh.

Conclusions

Various socio-economic factors substantially influence the utilization of medical treatment for childhood illnesses. Therefore, to enhance equitable access to health care for children, interventions should be designed targeting children from households with low socio-economic status. Various awareness-raising health education programs, poverty alleviation programs especially for rural areas can contribute in this regard.
Vitamin D deficiency is associated with respiratory symptoms and airway wall thickening in smokers with and without COPD: a prospective cohort study
Authors:   the COPDGene Investigators, Ghosh Auyon J. , Moll Matthew , Hayden Lystra P. , Bon Jessica , Regan Elizabeth , Hersh Craig P.
Published: May 2020

Background

Previous studies have established a higher prevalence of vitamin D deficiency in patients with COPD, but the relationship between vitamin D levels and COPD exacerbations remains controversial. In addition, the effect of vitamin D levels on imaging characteristics remains mostly unexplored. Using cross-sectional and longitudinal follow up data from the COPDGene Study, we assessed the association between vitamin D levels on respiratory symptoms, exacerbations, and imaging characteristics. We hypothesized that vitamin D deficiency will be associated with worse respiratory-related outcomes.

Methods

Current and former smokers between ages 45–80 were enrolled the COPDGene Study. Subjects completed questionnaires, spirometry, six-minute walk test, and chest computed tomography scans. A subset of subjects had measurement of serum concentration of 25-hydroxyvitamin D (25(OH)D). Vitamin D deficiency was defined as serum concentration less than 20 ng/mL. Longitudinal follow up was conducted via a web-based or telephone questionnaire.

Results

Vitamin D levels were measured on 1544 current and former smokers, of which 981 subjects had sufficient vitamin D levels and 563 subjects had vitamin D deficiency. Subjects with vitamin D deficiency were younger with increased likelihood of being African American, being current smokers, having a lower percent predicted FEV1, and having COPD. Vitamin D deficiency was associated with worse quality of life, increased dyspnea, decreased exercise tolerance, and increased frequency of severe exacerbations. Vitamin D deficiency was also associated with increased segmental airway wall thickness on chest CT scans.

Conclusion

Vitamin D deficiency was associated with increased respiratory symptoms, decreased functional status, increased frequency of severe exacerbations, as well as airway wall thickening on chest CT scans. Further research is needed to determine the potential impact of vitamin D supplementation to improve disease outcomes.
A multicentre retrospective observational study on Polish experience of pirfenidone therapy in patients with idiopathic pulmonary fibrosis: the PolExPIR study
Authors: Majewski Sebastian , Białas Adam J. , Buchczyk Małgorzata , Gomółka Paweł , Górska Katarzyna , Jagielska-Len Hanna , Jarzemska Agnieszka , Jassem Ewa , Jastrzębski Dariusz , Kania Aleksander , Koprowski Marek , Krenke Rafał , Kuś Jan , Lewandowska Katarzyna , Martusewicz-Boros Magdalena M. , Roszkowski-Śliż Kazimierz , Siemińska Alicja , Sładek Krzysztof , Sobiecka Małgorzata , Szewczyk Karolina , Tomczak Małgorzata , Tomkowski Witold , Wiatr Elżbieta , Ziora Dariusz , Żołnowska Beata , Piotrowski Wojciech J.
Published: May 2020

Background

Pirfenidone is an antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis (IPF). The drug is available for Polish patients with IPF since 2017. The PolExPIR study aimed to describe the real-world data (RWD) on the Polish experience of pirfenidone therapy in IPF with respect to safety and efficacy profiles.

Methods

This was a multicentre, retrospective, observational study collecting clinical data of patients with IPF receiving pirfenidone from January 2017 to September 2019 across 10 specialized pulmonary centres in Poland. Data collection included baseline characteristics, pulmonary function tests (PFTs) results and six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), treatment persistence, and survival were also collected up to 24 months post-inclusion.

Results

A total of 307 patients receiving pirfenidone were identified for analysis. The mean age was 68.83 (8.13) years and 77% were males. The median time from the first symptoms to IPF diagnosis was 15.5 (9.75–30) months and from diagnosis to start of pirfenidone treatment was 6 (2–23) months. Patients were followed on treatment for a median of 17 (12–22.75) months. Seventy-four patients (24.1%) required dose adjustments and 35 (11.4%) were chronically treated with different than the full recommended dose. A total of 141 patients (45.92%) discontinued therapy due to different reasons including ADRs (16.61%), death (8.79%), disease progression (6.51%), patient’s own request (5.54%), neoplastic disease (3.91%) and lung transplantation (0.33%). Over up to 24 months of follow-up, the pulmonary function remained largely stable. The median annual decline in forced vital capacity (FVC) during the first year of pirfenidone therapy was −20 ml (−200–100) and during the second year was −120 ml (−340–30). Over a study period, 33 patients (10.75%) died.

Conclusions

The PolExPIR study is a source of longitudinal RWD on pirfenidone therapy in the Polish cohort of patients with IPF supporting its long-term acceptable safety and efficacy profiles and reinforce findings from the previous randomised clinical trials and observational studies.
Methodological strategies to engage young black and Latino heterosexual couples in sexual and reproductive health research
Authors: Lanier Yzette , Campo Alena , Lavarin Claudine , Toussaint Ashley , Gwadz Marya , Guilamo-Ramos Vincent
Published: May 2020

Background

Approaches that move beyond individuals and target couples may be an effective strategy for reducing sexual and reproductive health (SRH) disparities among adolescents and young adults (AYA). However, few researchers have attempted to recruit couples due to feasibility and methodological issues. This study aims to enhance implementation and methodological approaches to successfully engage heterosexual Black and Latino adolescent and young adult (AYA) couples in sexual reproductive health (SRH) research.

Methods

We developed a four-step approach to systematically engage AYA couples in a qualitative study examining factors that influence uptake of combination HIV prevention methods: 1) understanding barriers and facilitators to engaging AYA couples, (2) identifying AYAs living in geographic areas of HIV vulnerability, (3) recruiting and screening AYA couples, and (4) scheduling and completion of the interview session.

Results

Black and Latino youth aged 16 to 24 and their opposite sex romantic were recruited in the South Bronx, New York from September 2017–May 2018. Three hundred and seventy-two men and women completed screening procedures to determine eligibility for the index participant; 125 were eligible and enrolled into the study. Forty-nine nominated partners (NPs) participated in screening procedures and enrolled into the study. A total of 49 couples enrolled into the study; 23 couples completed study activities.

Conclusions

Developing a systematic recruitment plan aided in successfully engaging Black and Latino heterosexual youth. Nevertheless, barriers to study enrollment remained including locating eligible IPs and screening of the NP. Targeting both young men and women was an effective recruitment strategy. Moreover, dyadic strategies that allow for simultaneous interaction with both couple members may be a beneficial strategy to couples’ study enrollment and completion of study activities.
An automated aquatic rack system for rearing marine invertebrates
Authors: Henry Jonathan Q. , Lesoway Maryna P. , Perry Kimberly J.
Published: May 2020

Background

One hundred years ago, marine organisms were the dominant systems for the study of developmental biology. The challenges in rearing these organisms outside of a marine setting ultimately contributed to a shift towards work on a smaller number of so-called model systems. Those animals are typically non-marine organisms with advantages afforded by short life cycles, high fecundity, and relative ease in laboratory culture. However, a full understanding of biodiversity, evolution, and anthropogenic effects on biological systems requires a broader survey of development in the animal kingdom. To this day, marine organisms remain relatively understudied, particularly the members of the Lophotrochozoa (Spiralia), which include well over one third of the metazoan phyla (such as the annelids, mollusks, flatworms) and exhibit a tremendous diversity of body plans and developmental modes. To facilitate studies of this group, we have previously described the development and culture of one lophotrochozoan representative, the slipper snailCrepidula atrasolea, which is easy to rear in recirculating marine aquaria. Lab-based culture and rearing of larger populations of animals remain a general challenge for many marine organisms, particularly for inland laboratories.

Results

Here, we describe the development of an automated marine aquatic rack system for the high-density culture of marine species, which is particularly well suited for rearing filter-feeding animals. Based on existing freshwater recirculating aquatic rack systems, our system is specific to the needs of marine organisms and incorporates robust filtration measures to eliminate wastes, reducing the need for regular water changes. In addition, this system incorporates sensors and associated equipment for automated assessment and adjustment of water quality. An automated feeding system permits precise delivery of liquid food (e.g., phytoplankton) throughout the day, mimicking real-life feeding conditions that contribute to increased growth rates and fecundity.

Conclusion

This automated system makes laboratory culture of marine animals feasible for both large and small research groups, significantly reducing the time, labor, and overall costs needed to rear these organisms.
Mapping DNA interaction landscapes in psoriasis susceptibility loci highlights KLF4 as a target gene in 9q31
Authors: Ray-Jones Helen , Duffus Kate , McGovern Amanda , Martin Paul , Shi Chenfu , Hankinson Jenny , Gough Oliver , Yarwood Annie , Morris Andrew P. , Adamson Antony , Taylor Christopher , Ding James , Gaddi Vasanthi Priyadarshini , Fu Yao , Gaffney Patrick , Orozco Gisela , Warren Richard B. , Eyre Steve
Published: May 2020

Background

Genome-wide association studies (GWAS) have uncovered many genetic risk loci for psoriasis, yet many remain uncharacterised in terms of the causal gene and their biological mechanism in disease. This is largely a result of the findings that over 90% of GWAS variants map outside of protein-coding DNA and instead are enriched in cell type- and stimulation-specific gene regulatory regions.

Results

Here, we use a disease-focused Capture Hi-C (CHi-C) experiment to link psoriasis-associated variants with their target genes in psoriasis-relevant cell lines (HaCaT keratinocytes and My-La CD8+ T cells). We confirm previously assigned genes, suggest novel candidates and provide evidence for complexity at psoriasis GWAS loci. For one locus, uniquely, we combine further epigenomic evidence to demonstrate how a psoriasis-associated region forms a functional interaction with the distant (> 500 kb) KLF4 gene. This interaction occurs between the gene and active enhancers in HaCaT cells, but not in My-La cells. We go on to investigate this long-distance interaction further with Cas9 fusion protein-mediated chromatin modification (CRISPR activation) coupled with RNA-seq, demonstrating how activation of the psoriasis-associated enhancer upregulates KLF4 and its downstream targets, relevant to skin cells and apoptosis.

Conclusions

This approach utilises multiple functional genomic techniques to follow up GWAS-associated variants implicating relevant cell types and causal genes in each locus; these are vital next steps for the translation of genetic findings into clinical benefit.
Elevated TNFRSF4 gene expression is a predictor of poor prognosis in non-M3 acute myeloid leukemia
Authors: Gu Siyu , Zi Jie , Han Qi , Song Chunhua , Ge Zheng
Published: May 2020

Background

We used bioinformatic tools to dichotomize 157 non-M3 AML patients from the TCGA dataset based on the presence or absence of TP53 mutations, and screened out a key gene related to TP53 mutation for future analysis.

Methods

DEGs were analyzed by R package “DESeq2” and then run GSEA, GO enrichment, KEGG pathway and PPI network. Hub genes were selected out according to MCC. Log-rank (Mantel–Cox) test was used for survival analysis. Mann–Whitney U’s nonparametric t test and Fisher’s exact test was used for continuous and categorical variables respectively. p value< 0.05 was considered to be statistical significance.

Results

TNFRSF4 was final screened out as a key gene. Besides TP53 mutation (p = 0.0118), high TNFRSF4 was also associated with FLT3 mutation (p = 0.0102) and NPM1 mutation (p = 0.0024). Elevated TNFRSF4 was significantly related with intermediate (p = 0.0004) and poor (p = 0.0011) risk stratification as well as relapse statute (p = 0.0099). Patients with elevated TNFRSF4 expression had significantly shorter overall survival (median survival: 2.35 months vs. 21 months, p < 0.0001). Based on our clinical center data, TNFRSF4 expression was significantly higher in non-M3 AML patients than HDs (p = 0.0377) and MDS patients (EB-1, 2; p = 0.0017).

Conclusions

Elevated TNFRSF4 expression was associated with TP53, FLT3 and NPM1 mutation as well as poor clinical outcome. TNFRSF4 expression was significantly higher in non-M3 AML patients than HDs and MDS (EB-1, 2) patients. TNFRSF4 is need for future functional and mechanistic studies to investigate the role in non-M3 AML.
Association of 25-hydroxy vitamin D with asthma and its severity in children: a case–control study
Authors: Sharif Alireza , Haddad Kashani Hamed , Sharif Mohammad Reza
Published: May 2020

Background

Universally, asthma has high prevalence rates and this has led numerous studies done into its causes. Despite extensive study on asthma the association between 25-Hydroxy Vitamin D (25(OH) vit. D) and asthma remains uncertain. In this study, the associations of 25(OH) vit. D levels with asthma and with the severity of asthma were evaluated.

Methods

This was a case–control study performed in 2015 in the city of Isfahan. In this study 520 children were studied. Children with asthma were classified as cases and children who were referred for reasons other than respiratory problems and asthma were considered as controls. Serum 25 (OH) vit. D levels were then examined and compared between the two groups. Differences among groups were stated to be statistically significant when P-values < 0.05.

Results

There were 260 asthmatic children and 260 controls in the present study. The mean 25 (OH) vit. D levels in the case group was 25.5 ± 16.62 and  16.76 ± 31.40 the control group and this difference was statistically significant (P < 0.05). 25(OH) vit. D levels were found to be 28.05 ± 16.98 in non-severe asthma and 21.41 ± 15.20 in severe asthma. Consequently 25(OH) vit. D level had inverse relationship with asthma severity (P = 0.002).

Conclusions

As the results of this study showed, the lower level of 25(OH) vit. D correlated with the higher severity of asthma manifestations. Therefore, it is recommended that 25(OH) vit. D levels get routinely checked especially in severe asthma cases and if the deficiency presents, appropriate therapeutic measures be used to reduce the asthma severity.
The telomerase gene polymorphisms, but not telomere length, increase susceptibility to primary glomerulonephritis/end stage renal diseases in females
Authors: Sun Qing , Liu Junli , Cheng Guanghui , Dai Mingkai , Liu Jiaxi , Qi Zhenqiang , Zhao Jingjie , Li Wei , Kong Feng , Liu Gang , Björkholm Magnus , Xu Dawei
Published: May 2020

Background

Primary glomerulonephritis (GN) is the leading cause of chronic kidney disease (CKD) and frequently progresses into end stage renal diseases (ESRDs). Shorter leukocyte telomere length (LTL) has been implicated in the CKD susceptibility and diminished kidney function, however, it is unclear whether the variants in telomerase genes contribute to risk to GN/CKD/ESRD. Here we address this issue by determining their association with the genetic variants of rs12696304 at the telomerase RNA component (TERC) and rs2736100 at the telomerase reverse transcriptase (TERT) loci.

Methods

The study includes 769 patients (243 primary GN-derived CKD and 526 ESRD cases) and sex-/age-matched healthy controls. Genomic DNA was extracted from peripheral blood of both controls and patients. Genotyping of rs12696304 and rs2736100 variants was carried out using PCR-based assays. Leukocyte telomere length (LTL) was determined using quantitative PCR (qPCR).

Results

A significantly higher frequency of TERC rs12696304 G allele was observed in patients and associated with increased disease risk (C vs G: OR = 1.334, 95% CI 1.112–1.586, P = 0.001; CC + GC vs GG: OR = 1.334, 95% CI 1.122–1.586, P = 0.001). Further analyses showed that such significant differences were only present between female controls and patients (C vs G: OR = 1.483, 95% CI 1.140–1.929, P = 0.003; CC + GC vs CC: OR = 1.692, 95% CI 1.202–2.383, P = 0.003), but not males. There were no differences in rs2736100 variants between controls and patients, but female ESRD patients carried significantly higher C allele frequencies than did female controls (A vs C: OR = 1.306, 95% CI 1.005–1.698, P = 0.046; AA vs CC: OR = 1.781, 95% CI 1.033–3.070, P = 0.037). There was no difference in LTL between controls and patients.

Conclusions

Our results reveal that the TERC rs12696304 and TERT rs2736100 polymorphisms, but not LTL per se, contribute to GN/CDK/ESRD risk.
The neuroregenerative effects of topical decorin on the injured mouse cornea
Authors: Wu Mengliang , Downie Laura E. , Grover Liam M. , Moakes Richard J. A. , Rauz Saaeha , Logan Ann , Jiao Haihan , Hill Lisa J. , Chinnery Holly R.
Published: May 2020

Background

The cornea is innervated with a rich supply of sensory nerves that play important roles in ocular surface health. Any injury or pathology of the corneal nerves increases the risk of dry eye disease and infection. This study aims to evaluate the therapeutic potential of topical decorin to improve corneal nerve regeneration in a mouse model of sterile epithelial abrasion injury.

Methods

Bilateral central corneal epithelial abrasions (2-mm, Alger Brush) were performed on young C57BL/6 J mice to remove the corneal sensory nerves. Decorin, or vehicle, was applied topically, three times per day for 1 week or every 2 h for 6 h. Spectral-domain optical coherence tomography was performed to measure the abrasion area and corneal thickness. Wholemount immunofluorescence staining was used to assess sensory nerve regeneration (β-tubulin III) and immune cell density (CD45, Iba1, CD11c). To investigate the specific role of dendritic cells (DCs), Cx3cr1gfp/gfp mice, which spontaneously lack resident corneal epithelial DCs, were also investigated. The effect of prophylactic topical administration of recombinant human decorin (applied prior to the abrasion) was also investigated. Nerve tracing (NeuronJ software) was performed to compare recovery of basal nerve axons and superficial nerve terminals in the central and peripheral cornea.

Results

At 6 h after injury, topical decorin application was associated with greater intraepithelial DC recruitment but no change in re-epithelialisation or corneal thickness, compared to the vehicle control. One week after injury, sub-basal nerve plexus and superficial nerve terminal density were significantly higher in the central cornea in the decorin-treated eyes. The density of corneal stromal macrophages in the decorin-treated eyes and their contralateral eyes was significantly lower compared to saline-treated corneas. No significant improvement in corneal nerve regeneration was observed in Cx3cr1gfp/gfp mice treated with decorin.

Conclusions

Decorin promotes corneal epithelial nerve regeneration after injury. The neuroregenerative effect of topical decorin was associated with a higher corneal DC density during the acute phase, and fewer macrophages at the study endpoint. The corneal neuroregenerative effects of decorin were absent in mice lacking intraepithelial DCs. Together, these findings support a role for decorin in DC-mediated neuroregeneration following corneal abrasion injury.
Axl receptor tyrosine kinase is a regulator of apolipoprotein E
Authors: Zhao Wenchen , Fan Jianjia , Kulic Iva , Koh Cheryl , Clark Amanda , Meuller Johan , Engkvist Ola , Barichievy Samantha , Raynoschek Carina , Hicks Ryan , Maresca Marcello , Wang Qi , Brown Dean G. , Lok Alvin , Parro Cameron , Robert Jerome , Chou Hsien-Ya , Zuhl Andrea M. , Wood Michael W. , Brandon Nicholas J. , Wellington Cheryl L.
Published: May 2020

Alzheimer’s disease (AD), the leading cause of dementia, is a chronic neurodegenerative disease. Apolipoprotein E (apoE), which carries lipids in the brain in the form of lipoproteins, plays an undisputed role in AD pathophysiology. A high-throughput phenotypic screen was conducted using a CCF-STTG1 human astrocytoma cell line to identify small molecules that could upregulate apoE secretion. AZ7235, a previously discovered Axl kinase inhibitor, was identified to have robust apoE activity in brain microglia, astrocytes and pericytes. AZ7235 also increased expression of ATP-binding cassette protein A1 (ABCA1), which is involved in the lipidation and secretion of apoE. Moreover, AZ7235 did not exhibit Liver-X-Receptor (LXR) activity and stimulated apoE and ABCA1 expression in the absence of LXR. Target validation studies using AXL−/− CCF-STTG1 cells showed that Axl is required to mediate AZ7235 upregulation of apoE and ABCA1. Intriguingly, apoE expression and secretion was significantly attenuated in AXL-deficient CCF-STTG1 cells and reconstitution of Axl or kinase-dead Axl significantly restored apoE baseline levels, demonstrating that Axl also plays a role in maintaining apoE homeostasis in astrocytes independent of its kinase activity. Lastly, these effects may require human apoE regulatory sequences, as AZ7235 exhibited little stimulatory activity toward apoE and ABCA1 in primary murine glia derived from neonatal human APOE3 targeted-replacement mice. Collectively, we identified a small molecule that exhibits robust apoE and ABCA1 activity independent of the LXR pathway in human cells and elucidated a novel relationship between Axl and apoE homeostasis in human astrocytes.
Structural equation modeling the “control of gut overgrowth” in the prevention of ICU-acquired Gram-negative infection
Authors: Hurley James C.
Published: May 2020

Background

Conceptually, the “control of gut overgrowth” (COGO) is key in mediating prevention against infection with Gram-negative bacilli by topical antibiotic prophylaxis, a common constituent of selective digestive decontamination (SDD) regimens. However, the relative importance of the other SDD components, enteral and protocolized parenteral antibiotic prophylaxis, versus other methods of infection prevention and versus other contextual exposures cannot be resolved within individual studies.

Methods

Seven candidate generalized structural equation models founded on COGO concepts were confronted with Pseudomonas and Acinetobacter bacteremia as well as ventilator-associated pneumonia data derived from > 200 infection prevention studies. The following group-level exposures were included in the models: use and mode of antibiotic prophylaxis, anti-septic and non-decontamination methods of infection prevention; proportion receiving mechanical ventilation; trauma ICU; mean length of ICU stay; and concurrency versus non-concurrency of topical antibiotic prophylaxis study control groups.

Results

In modeling Pseudomonas and Acinetobacter gut overgrowth as latent variables, anti-septic interventions had the strongest negative effect against Pseudomonas gut overgrowth but no intervention was significantly negative against Acinetobacter gut overgrowth. Strikingly, protocolized parenteral antibiotic prophylaxis and concurrency each have positive effects in the model, enteral antibiotic prophylaxis is neutral, and Acinetobacter bacteremia incidences are high within topical antibiotic prophylaxis studies, moreso with protocolized parenteral antibiotic prophylaxis exposure. Paradoxically, topical antibiotic prophylaxis (moreso with protocolized parenteral antibiotic prophylaxis) appears to provide the strongest summary prevention effects against overall bacteremia and overall VAP.

Conclusions

Structural equation modeling of published Gram-negative bacillus infection data enables a test of the COGO concept. Paradoxically, Acinetobacter and Pseudomonas bacteremia incidences are unusually high among studies of topical antibiotic prophylaxis.
Evaluation of a ketogenic diet for improvement of neurological recovery in individuals with acute spinal cord injury: study protocol for a randomized controlled trial
Authors: Demirel Aynur , Li Jia , Morrow Casey , Barnes Stephen , Jansen Jan , Gower Barbara , Kirksey Keneshia , Redden David , Yarar-Fisher Ceren
Published: May 2020

Background

Therapies that significantly improve the neurological and functional recovery of individuals with spinal cord injury (SCI) are still urgently needed. The ketogenic diet (KD) has been shown to improve forelimb motor function in an SCI rat model, likely by reducing inflammation and cell death in the spinal cord. Furthermore, our recent pilot study in patients with SCI showed that, compared with a standard hospital diet (SD), 5 weeks of KD started during acute care improved upper extremity motor function and reduced serum levels of a neuroinflammatory blood protein. The primary goals of the current study are to: 1) show the safety and feasibility of administering a KD during acute care for SCI; 2) determine if consuming 5 weeks of a KD significantly improves motor and sensory functions, functional independence and glycemic control; and 3) quantify serum biomarkers that are linked to improvements in neurological recovery and functional independence via targeted proteomics.

Methods/design

In a single-masked, longitudinal, randomized, parallel-controlled study, a total of 60 eligible, acutely traumatic spinal cord injured (cervical 5 to thoracic 12) participants ranging in age from 18 to 60 years with American Spinal Injury Association impairment scale (AIS) grades A–C (AIS-A, sensorimotor complete; AIS-B, sensory incomplete/motor complete; and AIS-C, nonfunctional motor incomplete) are being enrolled. Neurological and functional examinations, resting energy expenditure, blood, urine, and stool collections, and protein analyses related to neurological recovery will be performed within 72 h of injury (baseline measure) and repeated after 5 weeks of KD or SD (discharge measure). We anticipate a completion rate of 80% with a total of 48 participants.

Discussion

Intervention with a more neuroprotective diet during acute care of SCI can be implemented anywhere in the world at low cost and without major regulatory hurdles. Better functional recovery will lead to a better quality of life and long-term health outcomes in individuals with SCI. While this study targets SCI, if successful it has the potential to improve neurological outcomes for individuals with various traumatic injuries.

Trial registration

NCT03509571 Registered on April 28, 2018.
Correction to: Response to: “Does ACPA-negative RA consist of subgroups related to sustained DMARD-free remission and serological markers at disease presentation” by Masi and Fleischmann
Authors: Boeters Debbie M. , van der Helm–van Mil Annette H. M.
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Recovery and purification of cellulolytic enzymes from Aspergillus fumigatus CCT 7873 using an aqueous two-phase micellar system
Authors: de Oliveira Júnior Sérgio Dantas , de Araújo Padilha Carlos Eduardo , de Asevedo Estefani Alves , de Macedo Gorete Ribeiro , dos Santos Everaldo Silvino
Published: May 2020

Purpose

In this study, an aqueous two-phase micellar system (ATPMS), formed by the non-ionic surfactant Triton X-114, was used to investigate the partitioning of cellulolytic enzymes produced by the filamentous fungus Aspergillus fumigatus CCT 7873.

Methods

Performance of the ATPMS on the partitioning of CMCase (activity on carboxymethyl cellulose) and FPase (activity on filter paper) was investigated by varying the temperature (35, 40, 45, 50, 55, 60, and 65 °C), enzyme crude extract concentration (20, 40, 60, and 80% w/w), and Triton X-114 concentration (2, 4, 6, and 8% w/w) and by adding different inorganic salts (NaCl, CaCl2, MgSO4, and MnSO4) in the system.

Results

An ATPMS formed with 8% (w/w) Triton X-114 and 40% (w/w) enzymatic crude extract at a system temperature of 55 °C was most favorable for partitioning the tested enzymes. Under these conditions, a purification factor for CMCase and FPase of 10.89 and 0.65 was reached, respectively. The addition of inorganic salts changed the distribution of enzymes. Of these, CaCl2 contributed to a higher distribution coefficient (50.0), whereas for FPase, the presence of MnSO4 in the system improved the purification factor to 3.94.

Conclusion

The highest values obtained for the yield and purification factors demonstrate that ATPMS is an interesting option for recovering and purifying cellulolytic enzymes.
Mesenchymal stem cells as a potential therapy for COVID-19
Authors: Liu Shan , Peng Danyi , Qiu Huijun , Yang Ke , Fu Zhou , Zou Lin
Published: May 2020

The outbreak of 2019 novel coronavirus disease (COVID-19) worldwide is becoming rapidly a major concern. The number of severe cases has increased dramatically worldwide, while specific treatment options are scarce. The main pathologic features of severe or critical COVID-19 were consistent with acute lung injure (ALI)/acute respiratory distress syndrome (ARDS), characterized by cellular fibromyxoid exudates, extensive pulmonary inflammation, pulmonary edema, and hyaline membrane formation. Mesenchymal stem cells (MSCs) can balance the inflammatory response and has been mentioned to be effective on ALI/ARDS from both infectious and noninfectious causes previously, presenting an important opportunity to be applied to COVID-19. In this commentary, we summarize the clinical trials of MSCs treatments on ALI/ARDS and raise MSCs as a hopefully alternative therapy for severe or critical COVID-19.
Historic tobacco legislation in Israel: a moment to celebrate
Authors: Rosen L. , Kislev S. , Bar-Zeev Y. , Levine H.
Published: May 2020

Background

Israel was once a leader in tobacco control, but fell behind other countries, particularly during the past decade, as smoking rates stagnated.

Text

Landmark tobacco control legislation, which banned advertising (with the exception of the print press) and limited marketing, was passed in Israel on Dec. 31rst, 2018. The changes occurred following years of attempts which culminated in successful last-minute efforts to promote the legislation just before the early disbanding of the 20th Knesset (Israeli Parliament). Regulations concerning marketing and advertising were substantially strengthened to address all tobacco, nicotine and smoking products. Digital media was included for the first time. Electronic cigarettes, which were previously largely unregulated, now fall under existing tobacco legislation. The changes overcame intense opposition from the tobacco lobby, and occurred despite the fact that the basic elements for prevention policy postulated by the Richmond model were not in place.

Conclusions

This legislation represents an important and long-awaited change in Israeli tobacco control policy. Many deficiencies in existing tobacco control regulation were overcome, and some measures went beyond current international regulations. The cohesive partnership between legislators, public health organizations and professionals, advocacy groups, academia, and leading journalists was critical to this success. The progress was lauded by the World Health Organization with its highest award for tobacco control, which was presented to Smoke Free Israel. This case study provides important lessons for up-to-date tobacco control policy, in the age of rapid global changes in the tobacco, vaping and nicotine landscape.
Validation of the wearable acceptability range scale for smart apparel
Authors: Nam Changhyun , Lee Young-A
Published: May 2020

The wearable acceptability range (WEAR) Scale has been a useful tool used in consumer behaviour and product development research to better identify the social acceptance of wearable devices. In this study, we aimed to introduce an extended WEAR Scale to the apparel field by (a) refining existing measurement items and (b) validating this scale for use with smart apparel. Using a quantitative research method, an online survey was conducted with a convenience sample of US consumers aged 18 years old and over. Total 663 usable data were obtained and used for the data analysis. NVivo, SPSS, and AMOS programs were used to perform (a) a content analysis of the open-ended questions to identify recurring phrases, (b) basic descriptive statistics, and (c) a structural equation model testing, here validating the WEAR Scale, respectively. A 4-factor, 15-item WEAR Scale validated for examining consumers’ acceptance of smart apparel. The four WEAR dimensions are smart apparel in relation to: (a) design and aesthetics (four items), (b) self-expression (four items), (c) consequences (three items), and (d) reflection (four items). The findings of this study show the importance of these dimensions for the social acceptance of smart apparel. Therefore, this scale will be useful for the practical application in the apparel industry by providing better understanding of various aspects that smart apparel should consider during the product design and development stage. The scale can also be integrated with other consumer behavioural concepts to develop an emerging theoretical framework for the studies on smart apparel. Limitations and implications for future research were also discussed.
A descriptive study of pain treatment and its follow-up in primary care of elderly patients after orthopaedic care
Authors: Caleres Gabriella , Midlöv Patrik , Bondesson Åsa , Modig Sara
Published: May 2020

Background

Pain treatment post orthopaedic care in the elderly is complicated and requires careful follow-up. Current guidelines state all patients prescribed opioids should have a plan for gradual reduction, with the treatment progressively reduced and ended if any pain remains after more than three months. How this works in primary care remains to be explored.

The aim was to describe pain treatment and its follow-up in primary care of elderly patients after orthopaedic care.

Methods

In this descriptive study, medical case histories were collected for patients ≥ 75 years, which were enrolled at two rural primary care units in southern Sweden, and were discharged from orthopaedic care. Pain medication follow-up plans were noted, as well as current pain medication at discharge as well as two, six and twelve weeks later.

Results

We included a total of 49 community-dwelling patients with medication aid from nurses in municipality care and nursing home residents, ≥ 75 years, discharged from orthopaedic care. The proportion of patients prescribed paracetamol increased from 28/49 (57%) prior to admission, to 38/44 (82%) after 12 weeks. The proportion of patients prescribed opioids increased from 5/49 (10%) to 18/44 (41%). Primary care pain medication follow-up plans were noted for 16/49 patients (33%).

Conclusions

Many patients still used pain medication 12 weeks after discharge, and follow-up plans were quite uncommon, which may reflect upon lacking follow-up of these patients in primary care.