bluuebunny/crossref_metadata_2025 huggingface dataset:
GsmPlot: a web server to visualize epigenome data in NCBI
Authors: Li Jia , Yin Yue , Zhang Mutian , Cui Jie , Zhang Zhenhai , Zhang Zhiyong , Sun Deqiang
Published: February 2020

Background

Epigenetic regulation is essential in regulating gene expression across a variety of biological processes. Many high-throughput sequencing technologies have been widely used to generate epigenetic data, such as histone modification, transcription factor binding sites, DNA modifications, chromatin accessibility, and etc. A large scale of epigenetic data is stored in NCBI Gene Expression Omnibus (GEO). However, it is a great challenge to reanalyze these large scale and complex data, especially for researchers who do not specialize in bioinformatics skills or do not have access to expensive computational infrastructure.

Results

GsmPlot can simply accept GSM IDs to automatically download NCBI data or can accept user’s private bigwig files as input to plot the concerned data on promoters, exons or any other user-defined genome locations and generate UCSC visualization tracks. By linking public data repository and private data, GsmPlot can spark data-driven ideas and hence promote the epigenetic research.

Conclusions

GsmPlot web server allows convenient visualization and efficient exploration of any NCBI epigenetic data in any genomic region without need of any bioinformatics skills or special computing resources. GsmPlot is freely available at https://gsmplot.deqiangsun.org/.
Genetic diversity and population structure analysis based on the high density SNP markers in Ethiopian durum wheat (Triticum turgidum ssp. durum)
Authors: Alemu Admas , Feyissa Tileye , Letta Tesfaye , Abeyo Bekele
Published: February 2020

Background

Ethiopia has been considered as a center of diversity and the second possible center of domestication of durum wheat. Genetic diversity and population structure analysis in the existing Ethiopian durum wheat germplasm have enormous importance in enhancing breeding effort and for sustainable conservation. Hence, 192 Ethiopian durum wheat accessions comprising 167 landraces collected from major wheat-growing areas of the country and 25 improved varieties released from Debre Zeit and Sinana Agricultural Research Centers, Ethiopia in different years (1994–2010) were assembled for the current study.

Results

The panel was genotyped with a High-density 90 K wheat SNP array by Illumina and generated 15,338 polymorphic SNPs that were used to analyze the genetic diversity and to estimate the population structure. Varied values of genetic diversity indices were scored across chromosomes and genomes. Genome-wide mean values of Nei’s gene diversity (0.246) and polymorphism information content (0.203) were recorded signifying the presence of high genetic diversity within this collection. Minor allele frequency of the genome varied with a range of 0.005 to 0.5 scoring a mean value of 0.175. Improved varieties clustered separately to landraces in population structure analysis resulted from STRUCTURE, PCA and neighbor joining tree. Landraces clustering was irrespective of their geographical origin signifying the presence of higher admixture that could arise due to the existence of historical exchanges of seeds through informal seed system involving regional and countrywide farming communities in Ethiopia.

Conclusions

Sustainable utilization and conservation of this rich Ethiopian durum wheat genetic resource is an irreplaceable means to cope up from the recurrent climate changes and biotic stresses happening widely and thereby able to keep meeting the demand of durum productivity for the ever-growing human population.
Characterization of plant growth-promoting rhizobacteria from perennial ryegrass and genome mining of novel antimicrobial gene clusters
Authors: Li Zhibo , Song Chunxu , Yi Yanglei , Kuipers Oscar P.
Published: February 2020

Background

Plant growth-promoting rhizobacteria (PGPR) are good alternatives for chemical fertilizers and pesticides, which cause severe environmental problems worldwide. Even though many studies focus on PGPR, most of them are limited in plant-microbe interaction studies and neglect the pathogens affecting ruminants that consume plants. In this study, we expand the view to the food chain of grass-ruminant-human. We aimed to find biocontrol strains that can antagonize grass pathogens and mammalian pathogens originated from grass, thus protecting this food chain. Furthermore, we deeply mined into bacterial genomes for novel biosynthetic gene clusters (BGCs) that can contribute to biocontrol.

Results

We screened 90 bacterial strains from the rhizosphere of healthy Dutch perennial ryegrass and characterized seven strains (B. subtilis subsp. subtilis MG27, B. velezensis MG33 and MG43, B. pumilus MG52 and MG84, B. altitudinis MG75, and B. laterosporus MG64) that showed a stimulatory effect on grass growth and pathogen antagonism on both phytopathogens and mammalian pathogens. Genome-mining of the seven strains discovered abundant BGCs, with some known, but also several potential novel ones. Further analysis revealed potential intact and novel BGCs, including two NRPSs, four NRPS-PKS hybrids, and five bacteriocins.

Conclusion

Abundant potential novel BGCs were discovered in functional protective isolates, especially in B. pumilus, B. altitudinis and Brevibacillus strains, indicating their great potential for the production of novel secondary metabolites. Our report serves as a basis to further identify and characterize these compounds and study their antagonistic effects against plant and mammalian pathogens.
Implementation of the Goal-directed Medication review Electronic Decision Support System (G-MEDSS)© into home medicines review: a protocol for a cluster-randomised clinical trial in older adults
Authors: Kouladjian O’Donnell Lisa , Sawan Mouna , Reeve Emily , Gnjidic Danijela , Chen Timothy F. , Kelly Patrick J. , Bell J. Simon , Hilmer Sarah N.
Published: February 2020

Background

Older people living in the community have a high prevalence of polypharmacy and are vulnerable to adverse drug events. Home Medicines Review (HMR) is a collaborative medication review service involving general practitioners (GPs), accredited clinical pharmacists (ACPs) and patients, which aims to prevent medication-related problems. This study aims to evaluate the implementation of a Computerised Clinical Decision Support System (CCDSS) called G-MEDSS© (Goal-directed Medication Review Electronic Decision Support System) in HMRs to deprescribe anticholinergic and sedative medications, and to assess the effect of deprescribing on clinical outcomes.

Methods

This study consists of 2 stages: Stage I – a two-arm parallel-group cluster-randomised clinical trial, and Stage II – process evaluation of the CCDSS intervention in HMR. Community-dwelling older adults living with and without dementia who are referred for HMR by their GP and recruited by ACPs will be included in this study. G-MEDSS is a CCDSS designed to provide clinical decision support for healthcare practitioners when completing a medication review, to tailor care to meet the patients’ goals and preferences. The G-MEDSS contains three tools: The Goals of Care Management Tool, The Drug Burden Index (DBI) Calculator©, and The revised Patients’ Attitudes Towards Deprescribing (rPATD) questionnaire. The G-MEDSS produces patient-specific deprescribing reports, to be included as part of the ACPs communication with the patient’s GP, and patient-specific reports for the patient (or carer). ACPs randomised to the intervention arm of the study will use G-MEDSS to create deprescribing reports for the referring GP and for their patient (or carer) when submitting the HMR report. ACPs in the comparison arm will provide the usual care HMR service (without the G-MEDSS).

Outcomes

The primary outcome is reduction in DBI exposure 3 months after HMR ± G-MEDSS intervention between comparison and intervention groups. The secondary outcomes include changes in clinical outcomes (physical and cognitive function, falls, institutionalisation, GP visits, medication adherence and mortality) 3-months after HMR.

Discussion

This study is expected to add to the evidence that the combination of CCDSS supporting medication review can improve prescribing and clinical outcomes in older adults.

Trial registration

The trial was registered on the Australian New Zealand Clinical Trials Registry ACTRN12617000895381 on 19th June 2017.
Annual and seasonal patterns in etiologies of pediatric community-acquired pneumonia due to respiratory viruses and Mycoplasma pneumoniae requiring hospitalization in South Korea
Authors:   Pneumonia and Respiratory Disease Study Group of Korean Academy of Pediatric Allergy and Respiratory Disease, Lee Eun , Kim Chul-Hong , Lee Yong Ju , Kim Hyo-Bin , Kim Bong-Seong , Kim Hyung Young , Kim Yunsun , Kim Sangyoung , Park Chorong , Seo Ju-Hee , Sol In Suk , Sung Myongsoon , Song Min Seob , Song Dae Jin , Ahn Young Min , Oh Hea Lin , Yu Jinho , Jung Sungsu , Lee Kyung Suk , Lee Ju Suk , Jang Gwang Cheon , Jang Yoon-Young , Chung Eun Hee , Chung Hai Lee , Choi Sung-Min , Choi Yun Jung , Han Man Yong , Shim Jung Yeon , Kim Jin Tack , Kim Chang-Keun , Yang Hyeon-Jong
Published: February 2020

Background

Community–acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization.

Methods

We conducted a retrospective study in 30,994 children (aged 0–18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as macrolide-sensitive MP, macrolide-less effective MP (MLEP), and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests.

Results

MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.4% of the total MP pneumonia. In children < 2 years of age, RSV (34.0%) was the most common cause of CAP, followed by MP (9.4%); however, MP was the most common cause of CAP in children aged 2–18 years of age (45.3%). Systemic corticosteroid was most commonly administered for MP pneumonia. The rate of hospitalization in intensive care units was the highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia.

Conclusions

The present study provides fundamental data to establish public health policies to decrease the disease burden due to CAP and improve pediatric health.
Factors associated with Salmonella infection in patients with gastrointestinal complaints seeking health care at Regional Hospital in Southern Highland of Tanzania
Authors: Ngogo Fadhili A. , Joachim Agricola , Abade Ahmed M. , Rumisha Susan F. , Mizinduko Mucho M. , Majigo Mtebe V.
Published: February 2020

Background

Salmonellosis remains an important public health problem globally. The disease is among the leading causes of morbidity and mortality in developing countries that experience poor hygiene and lack of access to clean and safe water. There was an increase in reported cases of Salmonellosis in Njombe Region, Southern Highland of Tanzania between 2015 and 2016 based on clinical diagnosis. Nevertheless, little is known about the factors contributing to the transmission of this disease in the region. This study was conducted to determine the prevalence, antimicrobial susceptibility, and factors associated with Salmonella infection among patients who report gastrointestinal complaints.

Methods

A cross-sectional study was conducted from December 2017 to February 2018 among patients with gastrointestinal complaints at Kibena Regional Hospital. Stool samples were submitted for isolation of Salmonella spp. Identification was based on conventional biochemical tests and serotyping to differentiate typhoid and non-typhoid Salmonella (NTS). Antimicrobial susceptibility was performed using the Kirby-Bauer disc diffusion method. Multivariable logistic regression analysis was performed to examine the factors independently associated with Salmonella infection.

Results

The prevalence of Salmonella infection among participants with gastrointestinal complaints was 16.5% (95% CI: 12.7–21.1) of them, 83.7, 95% CI: 70.9–91.5 were NTS while 16.3, 95% CI: 8.5–29.0 were Typhoid Salmonella species.

All isolates were sensitive to ceftriaxone and ciprofloxacin, whereas 27.8 and 100% were resistant to co-trimoxazole and ampicillin respectively. The odd of Salmonella infection was fourfold higher among participants with formal employment (AOR 3.8, 95% CI, 1.53–9.40). Use of water from wells/rivers (AOR 2.2, 95% CI, 1.07–4.45), drinking untreated water (AOR 2.6, 95% CI, 1.21–5.48) and often eating at a restaurant (AOR 3.4, 95% CI, 1.28–8.93) had increased odds of Salmonella infection. Likewise, having abdominal pain (AOR 8.5, 95% CI, 1.81–39.78) and diarrhea (AOR 2.3, 95% CI, 1.12–4.68) were independent symptoms that predict Salmonella infection.

Conclusion

There is a high prevalence of Salmonella infection among people who report gastrointestinal complaints and it is clinically predicated by diarhoea and abdominal pain. Employed participants and those eating at restaurant and drinking unsafe water had higher risk of infection. Salmonella spp. causing gastroenteritis has developed resistance to commonly used antibiotics.
Rapid reduction of high-level pre-formed donor-specific antibodies after simultaneous liver-kidney transplantation: a report of two cases
Authors: Lai Christina , Newman Allyson , Mawson Jane , Abou-Daher Frederika , Watson Narelle , Majumdar Avik , Wyburn Kate , Chadban Steve , Gracey David
Published: February 2020

Background

Kidney transplantation performed in the presence of high-titre donor-specific antibodies (DSA) may result in hyper-acute or accelerated antibody-mediated rejection and rapid allograft loss. Previous studies have shown that this risk may be mitigated with simultaneous liver-kidney transplantation (SLKT); however, the mechanisms are not well defined. Here we report the evolution of pre-formed, high-level DSAs in two highly sensitised SLKT recipients peri-operatively and describe a profound sustained depletion of all DSAs from the time of liver anastomosis with no extra desensitisation therapy required.

Case presentation

Two patients underwent SLKT and received our centre’s standard renal transplant immunosuppression with basiliximab and methylprednisolone for induction therapy and prednisolone, mycophenolate and tacrolimus for maintenance therapy. HLA antibody samples were collected pre-operatively, and immediately post-liver and post-kidney revascularisation, and then regularly in the post-transplant period. Complement Dependant Cytotoxicity (CDC) crossmatches were also performed. Both patients were highly sensitised with a PRA over 97%. One patient had a positive B- and T-cell crossmatch pre-transplant. These positive CDC crossmatches became negative and the level of pre-formed DSAs reduced profoundly and rapidly, within 3 h post-liver revascularisation. The reduction in pre-formed DSAs, regardless of subclass, was seen immediately post-liver revascularisation, before implantation of the renal allografts. No significant reduction in non-donor specific HLA-antibodies was observed. Both patients maintained good graft function with no rejection on kidney allograft protocol biopsies performed at 10-weeks post-transplant.

Conclusions

These cases support the protective immunoregulatory role of the liver in the setting of SLKT, with no extra desensitisation treatment given pre-operatively for these highly sensitised patients.
The incidence, risk factors, and long-term outcomes of acute kidney injury in hospitalized diabetic ketoacidosis patients
Authors: Chen Junzhe , Zeng Honghui , Ouyang Xia , Zhu Mingsheng , Huang Qiuyan , Yu Wenjuan , Ling Li , Lan Hui-yao , Xu Anping , Tang Ying
Published: February 2020

Background

Emerging evidence has demonstrated that acute kidney injury (AKI) is an important risk factor associated with increased morbidity and mortality in diabetic ketoacidosis (DKA) patients. The current study aimed to investigate the incidence rate, risk factors, long-term renal outcomes, and mortality in DKA patients with AKI.

Methods

A total of 179 patients diagnosed with DKA at Sun Yat-sen Memorial Hospital from January 2012 to January 2018 were included in the analysis. AKI was diagnosed according to the 2012 KDIGO criteria. Risk factors, long-term renal outcomes, and mortality were analyzed by logistic regression and Cox proportional hazards models.

Results

Among 179 DKA patients, 98 patients (54.75%) were diagnosed as AKI. Aging; increased blood glucose, serum uric acid and white blood cells; decreased serum pH and albumin; coma; and preexisting chronic kidney disease (CKD) were risk factors of AKI in patients with DKA. During follow-up, DKA patients with AKI showed more than a two-fold decline in eGFR within 1 year after discharge from the hospital when compared with non-AKI DKA patients. Furthermore, AKI was also an independent risk factor for poor long-term renal outcomes and mortality in DKA patients.

Conclusions

Multiple risk factors contribute to the development of AKI in DKA patients. AKI and advanced AKI stage are associated with rapid progressive CKD and long-term mortality in patients with DKA.
Myotonic dystrophy type 1 accompanied with normal pressure hydrocephalus: a case report and literature review
Authors: Wang Junyang , Liu Ming , Shang Wenjie , Chen Zhongqin , Peng Guoping
Published: February 2020

Background

Myotonic dystrophy type 1 (DM1) is the most common disease that can cause muscle weakness and atrophy among adults. Normal pressure hydrocephalus (NPH) is characterized by the triad of gait disturbance, cognitive impairment and urinary incontinence. The association between DM1 and NPH is extremely rare. We report a Chinese female patient with DM1 in association with NPH.

Case presentation

The patient presented with a history of 3-year of walking instability and cognitive impairment. Her brain MRI showed ventriculomegaly with normal cerebrospinal fluid (CSF) pressure and the CSF tap-test was positive, which indicated the diagnosis of probable NPH. DM1 was confirmed by genetic testing.

Conclusions

Four patients with DM1-NPH association were found before. The association between NPH and DM1 may not be just a coincidence, NPH may occur in DM1 later in life and it is vital to recognize the association as a shunt surgery may improve patients’ quality of life.
A qualitative study of the factors influencing recruitment to a pilot trial on the prevention of striae gravidarum
Authors: Brennan Miriam , Clarke Mike , Devane Declan , Dowling Maura
Published: February 2020

Background

Striae gravidarum are a common occurrence in pregnancy and many women use a topical product to prevent their development or lessen their appearance if they do develop. There is a lack of evidence on the effectiveness of many of the products used by women. This study arose from challenges in recruitment to a pilot randomised trial (ISRCTN trial registration number:76992326) designed to evaluate the feasibility of a definitive trial to compare a moisturising oil to no treatment in the prevention and reduction in severity of striae gravidarum. The study reported here explored the factors influencing recruitment to that pilot trial.

Methods

A qualitative descriptive study was undertaken involving primigravid women attending an Irish maternity hospital. Data were collected by semi-structured telephone interviews over a four-week period and analysed using the framework method of analysis. Fifteen interview transcripts were included in the analysis.

Results

Four main themes consisting of twelve categories were identified from the interview data. The themes focused on women’s prevention of stretch marks and their choice of anti-stretch mark product, who and what influenced that choice and influences on trial participation. In relation to influences on trial participation, the possibility of being randomised to the non- intervention or control group was a deterrent for many women.

Conclusions

The prevention of stretch marks is important to pregnant women, as is their choice of product to prevent them. Offering women the opportunity to be part of a trial that would be of low burden and would test a well-known product may optimise recruitment. However, reluctance to be randomised because of the possibility of being allocated to the non-intervention control group suggests that further work is needed in this field on how best to communicate uncertainty to potential participants.
IDentification of patients in need of general and specialised PALLiative care (ID-PALL©): item generation, content and face validity of a new interprofessional screening instrument
Authors: Teike Lüthi Fabienne , Bernard Mathieu , Beauverd Michel , Gamondi Claudia , Ramelet Anne-Sylvie , Borasio Gian Domenico
Published: February 2020

Background

Early identification of patients requiring palliative care is a major public health concern. A growing number of instruments exist to help professionals to identify these patients, however, thus far, none have been thoroughly assessed for criterion validity. In addition, no currently available instruments differentiate between patients in need of general vs. specialised palliative care, and most are primarily intended for use by physicians. This study aims to develop and rigorously validate a new interprofessional instrument allowing identification of patients in need of general vs specialised palliative care.

Methods

The instrument development involved four steps: i) literature review to determine the concept to measure; ii) generation of a set of items; iii) review of the initial set of items by experts to establish the content validity; iv) administration of the items to a sample of the target population to establish face validity. We conducted a Delphi process with experts in palliative care to accomplish step 3 and sent a questionnaire to nurses and physicians non-specialised in palliative care to complete step 4. The study was conducted in the French and Italian-speaking regions of Switzerland. An interdisciplinary committee of clinical experts supervised all steps.

Results

The literature review confirmed the necessity of distinguishing between general and specialised palliative care needs and of adapting clinical recommendations to these different needs. Thirty-six nurses and physicians participated in the Delphi process and 28 were involved in the face validity assessment. The Delphi process resulted in two lists: a 7-item list to identify patients in need of general PC and an 8-item list to identify specialised PC needs. The content and face validity were deemed to be acceptable by both the expert and target populations.

Conclusion

This instrument makes a significant contribution to the identification of patients with palliative care needs as it has been designed to differentiate between general and specialised palliative care needs. Moreover, diagnostic data is not fundamental to the use of the instrument, thus facilitating its use by healthcare professionals other than physicians, in particular nurses. Internal and criterion validity assessments are ongoing and essential before wider dissemination of the instrument.
A bioinformatics investigation into the pharmacological mechanisms of the effect of the Yinchenhao decoction on hepatitis C based on network pharmacology
Authors: Zhang Jingyuan , Liu Xinkui , Wu Jiarui , Zhou Wei , Tian Jinhui , Guo Siyu , Jia Shan Shan , Meng Ziqi , Ni Mengwei
Published: February 2020

Background

Globally, more than 170 million people are infected with hepatitis C virus, a major cause of cirrhosis and hepatocellular carcinoma. The Yinchenhao Decoction (YCHD) is a classic formula comprising three herbal medicines. This decoction have long been used in China for clinically treating acute and chronic infectious hepatitis and other liver and gallbladder damp heat-accumulation disorders.

Methods

In this study, we identified 32 active ingredients and 200 hepatitis C proteins and established a compound-predicted target network and a hepatitis C protein–protein interaction network by using Cytoscape 3.6.1. Then, we systematically analyzed the potential targets of the YCHD for the treatment of hepatitis C. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by the Kyoto Encyclopedia of Genes and Genomes and gene ontology analyses.

Results

This study adopted a network pharmacology approach, mainly comprising target prediction, network construction, module detection, functional enrichment analysis, and molecular docking to systematically investigate the mechanisms of action of the YCHD in hepatitis C. The targets of the YCHD in the treatment of hepatitis C mainly involved PIK3CG, CASP3, BCL2, CASP8, and MMP1. The module and pathway enrichment analyses showed that the YCHD had the potential to influence varieties of biological pathways, including the TNF signaling pathway, Ras signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, and pathways in cancer, that play an important role in the pathogenesis of hepatitis C.

Conclusion

The results of this study preliminarily verified the basic pharmacological effects and related mechanisms of the YCHD in the treatment of hepatitis C.
Assessment of effects of methylene blue on intestinal ischemia and reperfusion in a rabbit model: hemodynamic, histological and immunohistochemical study
Authors: Morgaz Juan , Ventura Sergio , Muñoz-Rascón Pilar , Navarrete Rocio , Pérez José , Granados María del Mar , Fernández-Sarmiento José Andrés , Domínguez Juan Manuel , Molina Verónica , Gómez-Villamandos Rafael J. , Zafra Rafael
Published: February 2020

Background

Intestinal ischemia-reperfusion (IR) is an important clinical occurrence seen in common diseases, such as gastric dilatation-volvulus in dogs or colic in horses. Limited data is available on the use of methylene blue in veterinary medicine for intestinal ischemia-reperfusion. The present study aimed to compare the hemodynamic, histopathological, and immunohistochemical effects of two doses of methylene blue in two rabbit model groups In one group, 5 mg/kg IV was administered, and in another, 20 mg/kg IV was administered following a constant rate infusion (CRI) of 2 mg/kg/h that lasted 6 h. All the groups, including a control group had intestinal ischemia-reperfusion. Immunohistochemical analysis was performed using caspase-3.

Results

During ischemia, hemodynamic depression with reduced perfusion and elevated lactate were observed. During reperfusion, methylene blue (MB) infusion generated an increase in cardiac output due to a positive chronotropic effect, an elevation of preload, and an intense positive inotropic effect. The changes in heart rate and blood pressure were significantly greater in the group in which methylene blue 5 mg/kg IV was administered (MB5) than in the group in which methylene blue 20 mg/kg IV dose was administered (MB20). In addition, lactate and stroke volume variations were significantly reduced, and vascular resistance was significantly elevated in the MB5 group compared with the control group and MB20 group. The MB5 group showed a significant decrease in the intensity of histopathological lesion scores in the intestines and a decrease in caspase-3 areas, in comparison with other groups.

Conclusions

MB infusion produced improvements in hemodynamic parameters in rabbits subjected to intestinal IR, with increased cardiac output and blood pressure. An MB dosage of 5 mg/kg IV administered at a CRI of 2 mg/kg/h exhibited the most protective effect against histopathological damage caused by intestinal ischemia-reperfusion. Further studies with MB in clinical veterinary pathologies are recommended to fully evaluate these findings.
The impact on incident tuberculosis by kidney function impairment status: analysis of severity relationship
Authors: Shu Chin-Chung , Wei Yu-Feng , Yeh Yi-Chun , Lin Hsien-Ho , Chen Chung-Yu , Wang Ping-Huai , Cheng Shih-Lung , Wang Jann-Yuan , Yu Chong-Jen
Published: February 2020

Background

The risk of tuberculosis (TB) in patients with impaired kidney function remains unclear by different stages of renal function impairment.

Methods

We retrospectively recruited all patients with kidney function in a tertiary-care referral center from January 2008 to December 2013 and followed them till December 2016. We defined the primary outcome as active TB development and analyzed the impact of kidney function impairment.

Results

During the study period, a total of 289,579 patients were enrolled for analysis, and of them, 1012 patients had active TB events in an average of 4.13 years of follow-up. According to kidney function impairment, the incidence rate of TB was similar in patients with no chronic kidney disease (CKD) or stage 1 and stage 2, and it increased apparently at stage 3a (167.68 per 100,000 person-years) to stage 3b, stage 4 and stage 5 (229.25, 304.95 and 349.29 per 100,000 person-years, respectively). In a Cox proportional hazard regression model, the dose response of TB risk among different stages of kidney function impairment increased significantly from CKD stage 3a to stage 5. Patients with long-term dialysis had a hazard ratio of 2.041 (1.092–3.815, p = 0.0254), which is similar to that of stage 4 CKD but lower than that of stage 5.

Conclusion

In patients with impaired kidney function, the risk of TB increases from CKD stage 3, and in stage 5, the risk is even higher than that of those receiving dialysis. Further strategies of TB control need to consider this high-risk group.
Phenotypic comparison between smoking and non-smoking chronic obstructive pulmonary disease
Authors: Salvi Sundeep S. , Brashier Bill B. , Londhe Jyoti , Pyasi Kanchan , Vincent Vandana , Kajale Shilpa S. , Tambe Sajid , Mandani Kuldeep , Nair Arjun , Mak Sze Mun , Madas Sapna , Juvekar Sanjay , Donnelly Louise E. , Barnes Peter J.
Published: February 2020

Background

Although COPD among non-smokers (NS-COPD) is common, little is known about this phenotype. We compared NS-COPD subjects with smoking COPD (S-COPD) patients in a rural Indian population using a variety of clinical, physiological, radiological, sputum cellular and blood biomarkers.

Methods

Two hundred ninety subjects (118 healthy, 79 S-COPD, 93 NS-COPD) performed pre- and post-bronchodilator spirometry and were followed for 2 years to study the annual rate of decline in lung function. Body plethysmography, impulse oscillometry, inspiratory-expiratory HRCT, induced sputum cellular profile and blood biomarkers were compared between 49 healthy, 45 S-COPD and 55 NS-COPD subjects using standardized methods. Spirometric response to oral corticosteroids was measured in 30 female NS-COPD patients.

Results

Compared to all male S-COPD subjects, 47% of NS-COPD subjects were female, were younger by 3.2 years, had greater body mass index, a slower rate of decline in lung function (80 vs 130 mL/year), more small airways obstruction measured by impulse oscillometry (p < 0.001), significantly less emphysema (29% vs 11%) on CT scans, lower values in lung diffusion parameters, significantly less neutrophils in induced sputum (p < 0.05) and tended to have more sputum eosinophils. Hemoglobin and red cell volume were higher and serum insulin lower in S-COPD compared to NS-COPD. Spirometric indices, symptoms and quality of life were similar between S-COPD and NS-COPD. There was no improvement in spirometry in NS-COPD patients after 2 weeks of an oral corticosteroid.

Conclusions

Compared to S-COPD, NS-COPD is seen in younger subjects with equal male-female predominance, is predominantly a small-airway disease phenotype with less emphysema, preserved lung diffusion and a slower rate of decline in lung function.
Patient safety in marginalised groups: a narrative scoping review
Authors: Cheraghi-Sohi Sudeh , Panagioti Maria , Daker-White Gavin , Giles Sally , Riste Lisa , Kirk Sue , Ong Bie Nio , Poppleton Aaron , Campbell Stephen , Sanders Caroline
Published: February 2020

Background

Marginalised groups (‘populations outside of mainstream society’) experience severe health inequities, as well as increased risk of experiencing patient safety incidents. To date however no review exists to identify, map and analyse the literature in this area in order to understand 1) which marginalised groups have been studied in terms of patient safety research, 2) what the particular patient safety issues are for such groups and 3) what contributes to or is associated with these safety issues arising.

Methods

Scoping review. Systematic searches were performed across six electronic databases in September 2019. The time frame for searches of the respective databases was from the year 2000 until present day.

Results

The searches yielded 3346 articles, and 67 articles were included. Patient safety issues were identified for fourteen different marginalised patient groups across all studies, with 69% (n = 46) of the studies focused on four patient groups: ethnic minority groups, frail elderly populations, care home residents and low socio-economic status. Twelve separate patient safety issues were classified. Just over half of the studies focused on three issues represented in the patient safety literature, and in order of frequency were: medication safety, adverse outcomes and near misses. In total, 157 individual contributing or associated factors were identified and mapped to one of seven different factor types from the Framework of Contributory Factors Influencing Clinical Practice within the London Protocol. Patient safety issues were mostly multifactorial in origin including patient factors, health provider factors and health care system factors.

Conclusions

This review highlights that marginalised patient groups are vulnerable to experiencing a variety patient safety issues and points to a number of gaps. The findings indicate the need for further research to understand the intersectional nature of marginalisation and the multi-dimensional nature of patient safety issues, for groups that have been under-researched, including those with mental health problems, communication and cognitive impairments. Such understanding provides a basis for working collaboratively to co-design training, services and/or interventions designed to remove or at the very least minimise these increased risks.

Trial registration

Not applicable for a scoping review.
Doublecortin undergo nucleocytoplasmic transport via the RanGTPase signaling to promote glioma progression
Authors: Ayanlaja Abiola Abdulrahman , Ji Guanquan , Wang Jie , Gao Yue , Cheng Bo , Kanwore Kouminin , Zhang Lin , Xiong Ye , Kambey Piniel Alphayo , Gao Dianshuai
Published: February 2020

Background

Nuclear translocation of several oncogenic proteins have previously been reported, but neither the translocation of doublecortin (DCX) nor the mechanism involved has been studied. DCX is a neuronal microtubule-associated protein (MAP) that is crucial for adult neurogenesis and neuronal migration and has been associated with poor prognosis in gliomas.

Methods

We probed DCX expression in different grades of glioma tissues and conventional cells via western blotting. Then we analyzed the expression pattern in the Oncomine cancer profiling database. Confocal Immunofluorescence was used to detect DCX expression in the cellular compartments, while subcellular fractionation was probed via western blotting. Pulse shape height analysis was utilized to verify DCX localization in a larger population of cells. Co-immunoprecipitation was used in detecting DCX-import receptors interactions. To probe for DCX functions, stable cells expressing high DCX expression or knockdown were generated using CRISPR-Cas9 viral transfection, while plasmid site-directed mutant constructs were used to validate putative nuclear localization sequence (NLS) predicted via conventional algorithms and comparison with classical NLSs. in-silico modeling was performed to validate DCX interactions with import receptors via the selected putative NLS. Effects of DCX high expression, knockdown, mutation, and/or deletion of putative NLS sites were probed via Boyden’s invasion assay and wound healing migration assays, and viability was detected by CCK8 assays in-vitro, while xenograft tumor model was performed in nude mice.

Results

DCX undergoes nucleocytoplasmic movement via the RanGTPase signaling pathway with an NLS located on the N-terminus between serine47-tyrosine70. This translocation could be stimulated by MARK’s phosphorylation of the serine 47 residue flanking the NLS due to aberrant expression of glial cell line-derived neurotrophic factor (GDNF). High expression and nuclear accumulation of DCX improve invasive glioma abilities in-vitro and in-vivo. Moreover, knocking down or blocking DCX nuclear import attenuates invasiveness and proliferation of glioma cells.

Conclusion

Collectively, this study highlights a remarkable phenomenon in glioma, hence revealing potential glioma dependencies on DCX expression, which is amenable to targeted therapy.

Graphical Abstract
Clusters of diet, physical activity, television exposure and sleep habits and their association with adiposity in preschool children: the EDEN mother-child cohort
Authors: Saldanha-Gomes Cécilia , Marbac Matthieu , Sedki Mohammed , Cornet Maxime , Plancoulaine Sabine , Charles Marie-Aline , Lioret Sandrine , Dargent-Molina Patricia
Published: February 2020

Background

Despite the growing interest in the relation between adiposity in children and different lifestyle clusters, few studies used a longitudinal design to examine a large range of behaviors in various contexts, in particular eating- and sleep-related routines, and few studies have examined these factors in young children. The objectives of this study were to identify clusters of boys and girls based on diet, sleep and activity-related behaviors and their family environment at 2 and 5 years of age, and to assess whether the clusters identified varied across maternal education levels and were associated with body fat at age 5.

Methods

At 2 and 5 years, respectively, 1436 and 1195 parents from the EDEN mother-child cohort completed a questionnaire including behavioral data. A latent class analysis aimed to uncover gender-specific behavioral clusters. Body fat percentage was estimated by anthropometric and bioelectrical impedance measurements. Association between cluster membership and body fat was assessed with mutivariable linear regression models.

Results

At 2 years, two clusters emerged that were essentially characterized by opposite eating habits. At 5 years, TV exposure was the most distinguishing feature, but the numbers and types of clusters differed by gender. An association between cluster membership and body fat was found only in girls at 5 years of age, with girls in the cluster defined by very high TV exposure and unfavorable mealtime habits (despite high outdoor playing and walking time) having the highest body fat. Girls whose mother had low educational attainment were more likely to be in this high-risk cluster. Girls who were on a cluster evolution path corresponding to the highest TV viewing time and the least favorable mealtime habits from 2 to 5 years of age had higher body fat at 5 years.

Conclusions

Efforts to decrease TV time and improve mealtime routines may hold promise for preventing overweight in young children, especially girls growing up in disadvantaged families. These preventive efforts should start as early in life as possible, ideally before the age of two, and should be sustained over the preschool years.
Reductions to main meal portion sizes reduce daily energy intake regardless of perceived normality of portion size: a 5 day cross-over laboratory experiment
Authors: Haynes Ashleigh , Hardman Charlotte A. , Halford Jason C. G. , Jebb Susan A. , Mead Bethan R. , Robinson Eric
Published: February 2020

Background

Smaller portions may help to reduce energy intake. However, there may be a limit to the magnitude of the portion size reduction that can be made before consumers respond by increasing intake of other food immediately or at later meals. We tested the theoretical prediction that reductions to portion size would result in a significant reduction to daily energy intake when the resulting portion was visually perceived as ‘normal’ in size, but that a reduction resulting in a ‘smaller than normal’ portion size would cause immediate or later additional eating.

Methods

Over three 5-day periods, daily energy intake was measured in a controlled laboratory study using a randomized crossover design (N = 30). The served portion size of the main meal component of lunch and dinner was manipulated in three conditions: ‘large-normal’ (747 kcal), ‘small-normal’ (543 kcal), and ‘smaller than normal’ (339 kcal). Perceived ‘normality’ of portion sizes was determined by two pilot studies. Ad libitum daily energy intake from all meals and snacks was measured.

Results

Daily energy intake in the ‘large-normal’ condition was 2543 kcals. Daily energy intake was significantly lower in the ‘small-normal’ portion size condition (mean difference − 95 kcal/d, 95% CI [− 184, − 6], p = .04); and was also significantly lower in the ‘smaller than normal’ than the ‘small-normal’ condition (mean difference − 210 kcal/d, 95% CI [− 309, − 111], p < .001). Contrary to predictions, there was no evidence that the degree of additional food consumption observed was greater when portions were reduced past the point of appearing normal in size.

Conclusions

Reductions to the portion size of main-meal foods resulted in significant decreases in daily energy intake. Additional food consumption did not offset this effect, even when portions were reduced to the point that they were no longer perceived as being normal in size.

Trial registration

Prospectively registered protocol and analysis plan: https://osf.io/natws/; retrospectively registered: https://clinicaltrials.gov/ct2/show/NCT03811210.
Neural networks and the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation in depression
Authors: Liu Chun-Hong , Yang Ming-Hao , Zhang Guang-Zhong , Wang Xiao-Xu , Li Bin , Li Meng , Woelfer Marie , Walter Martin , Wang Lihong
Published: February 2020

Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder (MDD). It has been postulated that acupuncture may achieve its treatment effects on MDD through suppression of vagal nerve inflammatory responses. Our previous research established that taVNS significantly increases amygdala–dorsolateral prefrontal cortex connectivity, which is associated with a reduction in depression severity. However, the relationship between taVNS and the central/peripheral functional state of the immune system, as well as changes in brain neural circuits, have not as yet been elucidated. In the present paper, we outline the anatomic foundation of taVNS and emphasize that it significantly modulates the activity and connectivity of a wide range of neural networks, including the default mode network, executive network, and networks involved in emotional and reward circuits. In addition, we present the inflammatory mechanism of MDD and describe how taVNS inhibits central and peripheral inflammation, which is possibly related to the effectiveness of taVNS in reducing depression severity. Our review suggests a link between the suppression of inflammation and changes in brain regions/circuits post taVNS.
Clozapine reduces infiltration into the CNS by targeting migration in experimental autoimmune encephalomyelitis
Authors: Robichon Katharina , Patel Vimal , Connor Bronwen , La Flamme Anne Camille
Published: February 2020

Background

Atypical antipsychotic agents, such as clozapine, are used to treat schizophrenia and other psychiatric disorders by a mechanism that is believed to involve modulating the immune system. Multiple sclerosis is an immune-mediated neurological disease, and recently, clozapine was shown to reduce disease severity in an animal model of MS, experimental autoimmune encephalomyelitis (EAE). However, the mode of action by which clozapine reduces disease in this model is poorly understood.

Methods

Because the mode of action by which clozapine reduces neuroinflammation is poorly understood, we used the EAE model to elucidate the in vivo and in vitro effects of clozapine.

Results

In this study, we report that clozapine treatment reduced the infiltration of peripheral immune cells into the central nervous system (CNS) and that this correlated with reduced expression of the chemokines CCL2 and CCL5 transcripts in the brain and spinal cord. We assessed to what extent immune cell populations were affected by clozapine treatment and we found that clozapine targets the expression of chemokines by macrophages and primary microglia. Furthermore, in addition to decreasing CNS infiltration by reducing chemokine expression, we found that clozapine directly inhibits chemokine-induced migration of immune cells. This direct target on the immune cells was not mediated by a change in receptor expression on the immune cell surface but by decreasing downstream signaling via these receptors leading to a reduced migration.

Conclusions

Taken together, our study indicates that clozapine protects against EAE by two different mechanisms; first, by reducing the chemoattractant proteins in the CNS; and second, by direct targeting the migration potential of peripheral immune cells.
Emergency general surgeons: the special forces of general surgery (the “navy seals paradigm”)
Authors: Catena Fausto , Biffl Walter , De Simone Belinda , Sartelli Massimo , Di Saverio Salomone , Kluger Yoram , Moore Ernest E. , Ansaloni Luca , Coccolini Federico
Published: February 2020

Emergency surgeons have a crucial role in bridging the gap of skills resulting from the well-known general surgery fragmentation. The multi-specialist general surgery approach is still necessary to define proper diagnosis and therapy priorities in an emergency. Governments have to find effective organizational solutions to maintain emergency general surgery standards of care and to improve them further.