bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal function in Ethiopian HIV-positive adults on antiretroviral treatment with and without tenofovir
Authors: Yilma Daniel , Abdissa Alemseged , Kæstel Pernille , Tesfaye Markos , Olsen Mette F. , Girma Tsinuel , Ritz Christian , Friis Henrik , Andersen Åse B. , Kirk Ole
Published: August 2020

Background

Limited data are available on the effect of antiretroviral treatment (ART) or Tenofovir disoproxil fumarate (TDF) on renal function in Ethiopians. We aimed to assess factors associated with renal function changes during the first year of ART with special focus on TDF.

Methods

HIV positive persons who were ≥ 18 years of age and eligible for ART initiation were recruited. Creatinine measurement to estimate glomerular filtration rate (eGFR) and spot urine analyses were performed at baseline and after 3, 6 and 12 months of ART. Univariate and multivariate linear regression and univariate logistic regression were used to determine factors associated with eGFR as continuous and categorical variable respectively. A linear mixed model was used to assess 12 month eGFR difference in TDF and non-TDF based regimen.

Result

Of 340 ART-naïve HIV patients with baseline renal function tests, 82.3% (279/339) were initiated on a TDF based ART regimen. All patients were on non-nucleoside reverse transcriptase inhibitors (NNRTI) based ART regimen. The median (IQR) change in eGFR with 12 months of ART was 0.8 (− 11.1; 10.0) ml/min/1.73m2. About 41 and 26.9% of HIV patients had a drop of greater than 3 and 10 mL/min/1.73 m2in eGFR at 12 month, respectively. However, none of the HIV patients declined to< 60 ml/min/1.73m2within 12 months. Moreover, none of the HIV patients had persistent proteinuria or glycosuria. Older HIV patients especially age > 45 years and those with unsuppressed viral load at 6 month of ART had a significantly lower eGFR at 12 months of ART initiation. However, there was no difference in 12 month eGFR between HIV patients initiated on TDF based regimen and non-TDF based regimen.

Conclusion

Renal function remained stable with no difference between HIV patients treated with TDF or non-TDF NNRTI based ART regimen over 12 months. However, older HIV patients and those with unsuppressed viral load deserve special focus on renal monitoring. Data on long-term safety of TDF (> 1 year) is still warranted in this population.
Impact of individual and neighborhood social capital on the physical and mental health of pregnant women: the Japan Environment and Children’s Study (JECS)
Authors: Morozumi Ryoko , Matsumura Kenta , Hamazaki Kei , Tsuchida Akiko , Takamori Ayako , Inadera Hidekuni ,   the Japan Environment and Children’s Study (JECS) Group, Kamijima Michihiro , Yamazaki Shin , Ohya Yukihiro , Kishi Reiko , Yaegashi Nobuo , Hashimoto Koichi , Mori Chisato , Ito Shuichi , Yamagata Zentaro , Inadera Hidekuni , Nakayama Takeo , Iso Hiroyasu , Shima Masayuki , Kurozawa Youichi , Suganuma Narufumi , Kusuhara Koichi , Katoh Takahiko
Published: August 2020

Background

Previous studies revealed positive, negative, and no influence of social capital on the health outcomes of pregnant women. It was considered that such differences were caused by the disparities of outcome measures and sample sizes between studies. Our chief aim was to verify the positive influence of social capital on the health condition of pregnant women using established health outcome measures and large-scale nationwide survey data.

Methods

We employed questionnaire survey data from 79,210 respondents to the Japan Environment and Children’s Study, and physical and mental component summary scores from the 8-Item Short-Form Health Survey as outcome measures. We estimated the effect of individual and neighborhood social capitals on physical and mental component summary scores. To consider the property that the richness of social capital would be generally determined by individual characteristics, and to estimate the causal influence of social capital on health without bias caused by said property, we adopted average treatment effect estimation with inverse probability weighting. Generally, average treatment effects are based on the difference of average outcomes between treated and untreated groups in an intervention. In this research, we reckoned individuals’ different levels of social capital as a kind of non-randomized treatment for respective individuals, and we applied average treatment effect estimation. The analysis regarded pregnant women with the lowest level of social capital as untreated samples and women with other levels of social capitals as treated samples.

Results

For mental component summary score, the maximum average treatment effects in the comparison between the lowest and highest levels of social capital were approximately 4.4 and 1.6 for individual and neighborhood social capital, respectively. The average treatment effects for the physical component summary score were negligible for both social capital types.

Conclusions

Social capital particularly contributes to improving mental component summary score in pregnant women. The likelihood of a mentally healthy pregnancy may be increased by enhancing social capital.
Spontaneous regression of ALK fusion protein-positive non-small cell lung carcinoma: a case report and review of the literature
Authors: Walls Maria , Walls Gerard M. , James Jacqueline A. , Crawford Kyle T. , Abdulkhalek Hossam , Lynch Tom B. , Peace Aaron J. , McManus Terry E. , Evans O. Rhun
Published: August 2020

Background

ALK-rearrangement is observed in < 5% non-small cell lung cancer (NSCLC) cases and prior to the advent of oral tyrosine kinase inhibitors, the natural history of oncogenic NSCLC was typically poor. Literature relating to regression of treatment-naïve NSCLC is limited, and regression without treatment has not been noted in the ALK-rearranged sub-population.

Case presentation

A 76 year old ‘never smoker’ female with an ALK-rearranged left upper lobe T2 N0 NSCLC experienced a stroke following elective DC cardioversion for new atrial fibrillation. Following a good recovery, updated imaging demonstrated complete regression of the left upper lobe lesion and a reduction of the previously documented mediastinal lymph node. Remaining atelectasis was non-avid on repeat PET-CT imaging, 8 months from the baseline PET-CT. When the patient developed new symptoms 6 months later a further PET-CT demonstrated FDG-avid local recurrence. She completed 55 Gy in 20 fractions but at 18 months post-radiotherapy there was radiological progression in the lungs with new pulmonary metastases and effusion and new bone metastases. Owing to poor performance status, she was not considered fit for targeted therapy and died 5 months later.

Conclusion

All reported cases of spontaneous regression in lung cancer have been collated within. Documented precipitants of spontaneous regression across tumour types include biopsy and immune reconstitution; stroke has not been reported previously. The favourable response achieved with radical radiotherapy alone in this unusual case of indolent oncogenic NSCLC reinforces the applicability of radiotherapy in locally advanced ALK-rearranged tumours, in cases not behaving aggressively. As a common embolic event affecting the neurological and pulmonary vasculature is less likely, an immune-mediated mechanism may underpin the phenomenon described in this patient, implying that hitherto unharnessed principles of immuno-oncology may have relevance in oncogenic NSCLC. Alternatively, high electrical voltage applied percutaneously adjacent to the tumour during cardioversion in this patient may have induced local tumour cell lethality.
Burden of pelvic organ prolapse in Ethiopia: a systematic review and meta-analysis
Authors: Gedefaw Getnet , Demis Asmamaw
Published: August 2020

Background

Pelvic organ prolapse can significantly affect a woman’s quality of life by compromising physical, social, psychological and sexual function. Pelvic organ disorders and its consequences have higher economic burden to the patient as well to the country. Therefore, this systematic review and met- analysis aimed to estimate the burden of POP in Ethiopia.

Methods

International databases (MEDLINE/Pub Med, Hinari, Scopus, Google scholar, African journals and literatures were searched and seven eligible cross sectional and two case control studies were included in this systematic review and meta-analysis. Eggers test and funnel plot were computed to check publication bias across the studies. Publication bias was computed using a funnel plot and eggers test. Heterogeneity of the studies was checked using Cochrane Q-test and I2 statistic. Subgroup analysis was computed for the evidence of heterogeneity.

Results

This systematic review and meta-analysis revealed that the overall national prevalence of pelvic organ prolapse in Ethiopia was 23.52% (95% CI: 61.04, 80.24). Being rural resident (AOR = 3.29; 95% CI: 1.38–7.85), I2 = 47.5%, P = 0.167), having < 18.5 BMI (AOR = 2.59; 95% CI: 1.53–4.4), I2 = 59.9%, P = 0.64), and age > 40(AOR = 7.43; 95% CI: 2.27–24.29), I2 = 75.9%, P = 0.016) were the associated risk factors for pelvic organ prolapse.

Conclusions

The pooled prevalence of pelvic organ prolapse was high. Residence, body mass index and age of the women were the predictors of pelvic organ prolpase. Creating awareness and identifying the modifiable and non modifiable risk factors for pelvic organ prolpase is a crucial strategy to prevent further complications and risk of operation.
Standardized ethanol extract of Tinospora crispa upregulates pro-inflammatory mediators release in LPS-primed U937 human macrophages through stimulation of MAPK, NF-κB and PI3K-Akt signaling networks
Authors: Haque Md. Areeful , Jantan Ibrahim , Harikrishnan Hemavathy , Ahmad Waqas
Published: August 2020

Background

Immunomodulatory effects of Tinospora crispa have been investigated due to its traditional use to treat several inflammatory disorders associated to the immune system. The present study reports the underlying mechanisms involved in the stimulation of 80% ethanol extract of T. crispa stems on pro-inflammatory mediators release in lipopolysaccharide (LPS)-primed U937 human macrophages via MyD88-dependent pathways.

Methods

Release of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and production of prostaglandin E2 (PGE2) were determined by using enzyme-linked immunosorbent assay (ELISA). Immunoblot technique was executed to determine the activation of MAPKs molecules, NF-κB, PI3K-Akt and cyclooxygenase-2 (COX-2) protein. Determination of pro-inflammatory cytokines and COX-2 relative gene expression levels was by performing the real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). A reversed-phase HPLC method was developed and validated to standardize the T. crispa extract and chemical profiling of its secondary metabolites was performed by LC-MS/MS.

Results

Qualitative and quantitative analyses of chromatographic data indicated that syringin and magnoflorine were found as the major components of the extract. T. crispa-treatment prompted activation of NF-κB by enhancing IKKα/β and NF-κB (p65) phosphorylation, and degradation of IκBα. The extract upregulated COX-2 protein expression, release of pro-inflammatory mediators and MAPKs (ERK, p38 and JNK) phosphorylation as well as Akt dose-dependently. T. crispa extract also upregulated the upstream signaling adaptor molecules, toll-like receptor 4 (TLR4) and MyD88. T. crispa-treatment also upregulated the pro-inflammatory markers mRNA expression.

Conclusion

The results suggested that T. crispa extract stimulated the MyD88-dependent signaling pathways by upregulating the various immune inflammatory related parameters.
A synthetic peptide sensitizes multi-drug resistant Pseudomonas aeruginosa to antibiotics for more than two hours and permeabilizes its envelope for twenty hours
Authors: Rázquin-Olazarán Iosu , Shahrour Hawraa , Martínez-de-Tejada Guillermo
Published: August 2020

Background

Pseudomonas aeruginosa is a Gram-negative pathogen that frequently causes life-threatening infections in immunocompromised patients. We previously showed that subinhibitory concentrations of short synthetic peptides permeabilize P. aeruginosa and enhance the lethal action of co-administered antibiotics.

Methods

Long-term permeabilization caused by exposure of multidrug-resistant P. aeruginosa strains to peptide P4–9 was investigated by measuring the uptake of several antibiotics and fluorescent probes and by using confocal imaging and atomic force microscopy.

Results

We demonstrated that P4–9, a 13-amino acid peptide, induces a growth delay (i.e. post-antibiotic effect) of 1.3 h on a multidrug-resistant P. aeruginosa clinical isolate. Remarkably, when an independently P4–9-treated culture was allowed to grow in the absence of the peptide, cells remained sensitive to subinhibitory concentrations of antibiotics such as ceftazidime, fosfomycin and erythromycin for at least 2 h. We designated this persistent sensitization to antibiotics occurring in the absence of the sensitizing agent as Post-Antibiotic Effect associated Permeabilization (PAEP). Using atomic force microscopy, we showed that exposure to P4–9 induces profound alterations on the bacterial surface and that treated cells need at least 2 h of growth to repair those lesions. During PAEP, P. aeruginosa mutants overexpressing either the efflux pump MexAB-OprM system or the AmpC β-lactamase were rendered sensitive to antibiotics that are known substrates of those mechanisms of resistance. Finally, we showed for the first time that the descendants of bacteria surviving exposure to a membrane disturbing peptide retain a significant level of permeability to hydrophobic compounds, including propidium iodide, even after 20 h of growth in the absence of the peptide.

Conclusions

The phenomenon of long-term sensitization to antibiotics shown here may have important therapeutic implications for a combined peptide-antibiotic treatment because the peptide would not need to be present to exert its antibiotic enhancing activity as long as the target organism retains sensitization to the antibiotic.
TAK-242 ameliorates DSS-induced colitis by regulating the gut microbiota and the JAK2/STAT3 signaling pathway
Authors: Wang Jiajia , Zhu Guannan , Sun Cheng , Xiong Kangwei , Yao Tingting , Su Yuan , Fang Haiming
Published: August 2020

Background

The goal of the present study was to investigate the effects of TAK-242 on the gut microbiota and the TLR4/JAK2/STAT3 signaling pathway in mice with dextran sulfate sodium (DSS)-induced colitis.

Results

At the phylum level,Bacteroidetes,Firmicutes,Actinobacteria,Cyanobacteria,EpsilonbacteraeotaandProteobacteriawere the primary microbiota in the five groups. TAK-242 treatment significantly enhancedVerrucomicrobiaandActinobacteria; significantly decreasedCyanobacteria, EpsilonbacteraeotaandProteobacteria; and particularly promoted the growth ofAkkermansia. TAK-242 markedly alleviated DSS-induced colitis symptoms and colonic lesions by promoting IL-10 release, inhibiting IL-17 release, downregulating TLR4 and JAK2/STAT3 mRNA and protein expression and increasing JAK2/STAT3 phosphorylation.

Conclusion

TAK-242 modulates the structure of the gut microbiota in colitis and may be a novel therapeutic candidate for ulcerative colitis.
Activation and enhancement of caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies
Authors: Xie Yunchang , Chen Jiawen , Wang Bo , Chen Tai , Chen Junyu , Zhang Yuan , Liu Xiaoying , Chen Qi
Published: August 2020

Background

Activation of silent biosynthetic gene clusters (BGCs) in marine-derived actinomycete strains is a feasible strategy to discover bioactive natural products. Actinoalloteichus sp. AHMU CJ021, isolated from the seashore, was shown to contain an intact but silent caerulomycin A (CRM A) BGC-cam in its genome. Thus, a genome mining work was preformed to activate the strain’s production of CRM A, an immunosuppressive drug lead with diverse bioactivities.

Results

To well activate the expression of cam, ribosome engineering was adopted to treat the wild type Actinoalloteichus sp. AHMU CJ021. The initial mutant strain XC-11G with gentamycin resistance and CRM A production titer of 42.51 ± 4.22 mg/L was selected from all generated mutant strains by gene expression comparison of the essential biosynthetic gene-camE. The titer of CRM A production was then improved by two strain breeding methods via UV mutagenesis and cofactor engineering-directed increase of intracellular riboflavin, which finally generated the optimal mutant strain XC-11GUR with a CRM A production titer of 113.91 ± 7.58 mg/L. Subsequently, this titer of strain XC-11GUR was improved to 618.61 ± 16.29 mg/L through medium optimization together with further adjustment derived from response surface methodology. In terms of this 14.6 folds increase in the titer of CRM A compared to the initial value, strain XC-GUR could be a well alternative strain for CRM A development.

Conclusions

Our results had constructed an ideal CRM A producer. More importantly, our efforts also had demonstrated the effectiveness of abovementioned combinatorial strategies, which is applicable to the genome mining of bioactive natural products from abundant actinomycetes strains.
Overexpression of GPX3, a potential biomarker for diagnosis and prognosis of breast cancer, inhibits progression of breast cancer cells in vitro
Authors: Lou Weiyang , Ding Bisha , Wang Shuqian , Fu Peifen
Published: August 2020

Background

Growing evidence has demonstrated that glutathione peroxidases (GPXs) family genes play critical roles in onset and progression of human cancer. However, a systematic study regarding expression, diagnostic and prognostic values, and function of GPXs family genes in breast cancer remains absent.

Materials and methods

Several databases were employed to perform in silico analyses for GPXs family genes. qRT-PCR, western blot and immunohistochemistry staining were introduced to validate GPX3 expression in breast cancer. The functions of GPX3 in breast cancer cells were successively determined.

Results

By combination of receiver operating characteristic (ROC) curve analysis, survival analysis and expression analysis, GPX3 was considered as a potential tumor suppressor and a promising diagnostic/prognostic biomarker in breast cancer. Next, low expression of GPX3 was confirmed in breast cancer cells and tissues when compared with corresponding normal controls. Overexpression of GPX3 markedly suppressed proliferation, colony formation, migration and invasion of breast cancer in vitro. Moreover, two potential mechanisms responsible for GPX3 downregulation in breast cancer, including hypermethylation of GPX3 promoter and release of hsa-miR-324-5p inhibition.

Conclusions

Collectively, we demonstrate that GPX3 is markedly downregulated in breast cancer, possesses significant diagnostic and prognostic values and attenuated in vitro growth and metastasis of breast cancer.
What do people benefit from a citizen science programme? Evidence from a Rwandan citizen science programme on malaria control
Authors: Asingizwe Domina , Poortvliet P. Marijn , van Vliet Arnold J. H. , Koenraadt Constantianus J. M. , Ingabire Chantal M. , Mutesa Leon , Leeuwis Cees
Published: August 2020

Background

Malaria control remains a challenge globally and in malaria-endemic countries in particular. In Rwanda, a citizen science programme has been set up to improve malaria control. Citizens are involved in collecting mosquito species and reporting mosquito nuisance. This study assessed what people benefit from such a citizen science programme. The analysis was conducted on how the citizen science programme influenced perceptions and behaviour related to malaria control.

Methods

This study employed a mixed-methods approach using dissemination workshops, a survey, and village meetings as the main data collection methods. Dissemination workshops and village meetings involved 112 volunteers of the citizen science programme and were conducted to explore: (1) the benefits of being involved in the programme and (2) different ways used to share malaria-related information to non-volunteers. The survey involved 328 people (110 volunteers and 218 non-volunteers) and was used to compare differences in malaria-related perceptions and behaviour over time (between 2017 and 2019), as well as between volunteers and non-volunteers.

Results

Malaria-related perceptions and behaviour changed significantly over time (between 2017 and 2019) and became favourable to malaria control. When the findings were compared between volunteers and non-volunteers, for perceptions, only perceived self-efficacy showed a significant difference between these two groups. However, volunteers showed significantly more social interaction, participation in malaria-related activities at the community level, and indoor residual spraying (IRS) acceptance. In addition, both volunteers and non-volunteers reported to have gained knowledge and skills about the use of malaria control measures in general, and mosquito species in particular among volunteers.

Conclusion

The reported knowledge and skills gained among non-volunteers indicate a diffusion of the citizen science programme-related information in the community. Thus, the citizen science programme has the potential to provide individual and collective benefits to volunteers and society at large.
Psychosocial resources developed and trialled for Indigenous people with autism spectrum disorder and their caregivers: a systematic review and catalogue
Authors: Shochet Ian M. , Orr Jayne A. , Kelly Rachel L. , Wurfl Astrid M. , Saggers Beth R. , Carrington Suzanne B.
Published: August 2020

Background

People with autism spectrum disorder (ASD) face many psychosocial challenges throughout life, highlighting the need for programs and resources promoting psychosocial wellbeing. Indigenous peoples with ASD and/or other neurodevelopmental disorders must overcome cultural and social barriers to access such supports. This study aimed to identify psychosocial programs and resources developed world-wide for this population by systematically reviewing research evaluating programs aiming to promote the psychosocial wellbeing of this population and/or their caregivers; and collating and reviewing resources developed to promote their psychosocial wellbeing.

Methods

Searches were last conducted in December 2019. The systematic review searched 28 electronic databases, and 25 electronic databases were searched for resources promoting psychosocial wellbeing. Additional published and unpublished studies were identified from relevant reviews, authors of eligible articles, and experts working in Indigenous Health. Articles and resources were screened for inclusion using pre-defined criteria. Articles included in the systematic review were assessed for quality using the Mixed Methods Assessment Tool. The diversity and paucity of outcomes reported precluded pooling of study findings for meta-analysis.

Results

Seven articles situated in the USA (2), Canada (3) and Australia (2); and eleven resources developed in Australia (9), Canada (1) and New Zealand (1) met inclusion criteria. All articles showed some promising findings for improving psychosocial wellbeing for Indigenous children with ASD and/or another neurodevelopmental disorder, and 5 of 7 evaluated the cultural adaptation of an existing evidence-based program for an Indigenous population. However, methodological quality was moderate or low (57% and 43% of articles respectively) and no studies had adult participants. The psychosocial wellbeing supports provided by the 11 resources included psychoeducation, community support, and services/workshops.

Conclusions

Despite the paucity of research and resources found, important exemplars demonstrate that existing programs can be adapted to support Indigenous people with ASD and other neurodevelopmental disorders. While future policy should endeavour to facilitate Indigenous people’s access to support services, and encourage researchers to develop and evaluate programs promoting psychosocial wellbeing for this population, given complexities of designing and evaluating new programs, careful and appropriate cultural adaptations of existing evidence-based programs would increase feasibility of ongoing research without compromising outcomes.
Contribution of CYP24A1 variants in coronary heart disease among the Chinese population
Authors: Qian Peng , Cao Xuanchao , Xu Xianjing , Duan Mingqin , Zhang Qian , Huang Gairong
Published: August 2020

Background

Cytochrome P450 (CYPs) participate in the mechanisms of cardiovascular disease. The purpose of this research was to evaluate the contributions of CYP24A1 variants to coronary heart disease (CHD) among the Chinese Han population.

Methods

This study included 505 CHD cases and 508 controls. Four variants of CYP24A1 (rs2762934, rs1570669, rs6068816 and rs2296241) were chosen and genotyped by the Agena MassARRAY system among the Chinese population. The linkage between CYP24A1 variants and CHD risk were assessed by logistic regression to compute the odds ratio (OR) and 95% confidence interval (CI). Then, multifactor dimensionality reduction (MDR) was applied to analyze the interactions of CYP24A1 variants.

Results

The results of this study showed that CYP24A1 rs6068816 significantly enhanced CHD risk in multiple genetic models (allele: P = 0.014; codominant: P = 0.015; dominant: P = 0.043; recessive: P = 0.040; additive: P = 0.013), whereas rs2296241 was likely to protect individuals from CHD (codominant: P = 0.019; recessive: P = 0.013; additive: P = 0.033). Stratification analysis revealed that CYP24A1 polymorphisms had strong relationships with CHD risk that were dependent on age, sex, Gensini grade and smoking status (P <  0.05). Moreover, a four-locus model (rs2762934, rs1570669, rs6068816 and rs2296241) had significant impact on CHD risk in MDR analysis.

Conclusion

It revealed that CYP24A1 variants were significantly linked with CHD susceptibility in the Chinese population.
Chinese validation and clinical application of the tinnitus functional index
Authors: Wang Xianren , Zeng Ruyan , Zhuang Huiwen , Sun Qiyang , Yang Zijun , Sun Cangjian , Xiong Guanxia
Published: August 2020

Objective

The Tinnitus Functional Index (TFI) is a new diagnostic measure of the functional impact of tinnitus that is also a sensitive measure of treatment-related changes. However, the TFI has not been translated into Chinese and fully validated in China. The aim of the present study was to evaluate the validity of a Chinese version of the TFI as a diagnostic measure of tinnitus severity in a sample of Chinese patients and to verify the value of its clinical application in China.

Design

A sample of 206 patients whose primary complaint was tinnitus was used to analyze the reliability and validity of the TFI. In addition, patients were asked to fill out the Tinnitus Handicap Inventory (THI) and the Center for Epidemiologic Studies-Depression Scale (CES-D), the Beck Anxiety Inventory (BAI), and the Satisfaction With Life Scale (SWLS) to compare TFI with their association. The internal consistency of the TFI was assessed with Cronbach’s alpha coefficient. The factor structure of the TFI was assessed by Exploratory Factor Analysis (EFA). The extracted factors were compared to those of the original TFI scale.

Results

The reliability of the Chinese version of the TFI (Cronbach’ s α = .969) showed high internal consistency. The exploratory factor analysis (EFA) of the TFI showed that six factors with one main factor could be extracted instead of eight factors as described in the original version. Nevertheless, relations to the original eight subscales could be demonstrated. A high correlation between the TFI and the THI (r = .865, p < 0.01) and lower correlations between the TFI and the CES-D (r = .334, p < 0.01), BAI (r = .559, p < 0.01), and SWLS (r = − 0.324, p < 0.01) confirmed the satisfactory convergent and discriminant validity of the TFI.

Conclusion

After translated and validated a Chinese version of the TFI and found that the TFI had high reliability and validity, which means both instruments are reliable instruments to assess the severity of tinnitus in clinical applications in China.
The opioid crisis: a contextual, social-ecological framework
Authors: Jalali Mohammad S. , Botticelli Michael , Hwang Rachael C. , Koh Howard K. , McHugh R. Kathryn
Published: August 2020

The prevalence of opioid use and misuse has provoked a staggering number of deaths over the past two and a half decades. Much attention has focused on individual risks according to various characteristics and experiences. However, broader social and contextual domains are also essential contributors to the opioid crisis such as interpersonal relationships and the conditions of the community and society that people live in. Despite efforts to tackle the issue, the rates of opioid misuse and non-fatal and fatal overdose remain high. Many call for a broad public health approach, but articulation of what such a strategy could entail has not been fully realised. In order to improve the awareness surrounding opioid misuse, we developed a social-ecological framework that helps conceptualise the multivariable risk factors of opioid misuse and facilitates reviewing them in individual, interpersonal, communal and societal levels. Our framework illustrates the multi-layer complexity of the opioid crisis that more completely captures the crisis as a multidimensional issue requiring a broader and integrated approach to prevention and treatment.
Transformation of the Taiwan Biobank 3.0: vertical and horizontal integration
Authors: Lin Jui-Chu , Hsiao Wesley Wei-Wen , Fan Chien-Te
Published: August 2020

Researchers expect a high quality of biospecimens/data and value-added services from biobanks. Therefore, the concept of “biobank 3.0” was introduced so that biobanks could better meet the needs of stakeholders and maintain sustainable operations. Theoretically, the Taiwan Biobank (TWB) has already gone through the concepts of biobank 1.0 and 2.0. However, three challenges still need to be addressed before it can be transformed into a new generation of the TWB (namely, the TWB 3.0): (1) the difficulty of integrating other biobanks’ resources, (2) the efficiency and effectiveness of the release and use of biospecimens/data, and (3) the development of income and revenue models of sustainability. To address these issues, this paper proposes a framework for the TWB 3.0 transformation based on a dual-pillar approach composed of a “physically” vertical integration driven by the TWB and a “virtually” horizontal network led by the National Health Research Institutes (NHRI) of Taiwan. Using prominent biobanks such as the Biobanking and BioMolecular Resources Research Infrastructure-European Research Infrastructure Consortium (BBMRI-ERIC), the UK Biobank, and the National Institutes of Health (NIH)’s All of Us Research Program as models, the TWB can strengthen its on-going TWB 2.0 operations in regional and/or international collaboration, increase the value of data collected and develop closer relationships with biobank participants and users. To these ends, the authors highlight key issues that include, but are not limited to, the harmonization of relevant ELSI standards for various biobanks’ integrations; the value-added services and the efficiency of Big Data Era related research and/or precision medicine development, and financial concerns related to biobank sustainability. This paper concludes by discussing how greater participant engagement and the uptake of Information Technology (IT) and Artificial Intelligence (AI) applications can be used in partnership with vertical and horizontal integration as part of a four-pronged approach to promote biobank sustainability, and facilitate the TWB 3.0 transformation.
Central nervous system complications associated with SARS-CoV-2 infection: integrative concepts of pathophysiology and case reports
Authors: Najjar Souhel , Najjar Amanda , Chong Derek J. , Pramanik Bidyut K. , Kirsch Claudia , Kuzniecky Ruben I. , Pacia Steven V. , Azhar Salman
Published: August 2020

Coronavirus disease 2019 (COVID-19) is a highly infectious pandemic caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It frequently presents with unremitting fever, hypoxemic respiratory failure, and systemic complications (e.g., gastrointestinal, renal, cardiac, and hepatic involvement), encephalopathy, and thrombotic events. The respiratory symptoms are similar to those accompanying other genetically related beta-coronaviruses (CoVs) such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East Respiratory Syndrome CoV (MERS-CoV). Hypoxemic respiratory symptoms can rapidly progress to Acute Respiratory Distress Syndrome (ARDS) and secondary hemophagocytic lymphohistiocytosis, leading to multi-organ system dysfunction syndrome. Severe cases are typically associated with aberrant and excessive inflammatory responses. These include significant systemic upregulation of cytokines, chemokines, and pro-inflammatory mediators, associated with increased acute-phase proteins (APPs) production such as hyperferritinemia and elevated C-reactive protein (CRP), as well as lymphocytopenia. The neurological complications of SARS-CoV-2 infection are high among those with severe and critical illnesses. This review highlights the central nervous system (CNS) complications associated with COVID-19 attributed to primary CNS involvement due to rare direct neuroinvasion and more commonly secondary CNS sequelae due to exuberant systemic innate-mediated hyper-inflammation. It also provides a theoretical integration of clinical and experimental data to elucidate the pathogenesis of these disorders. Specifically, how systemic hyper-inflammation provoked by maladaptive innate immunity may impair neurovascular endothelial function, disrupt BBB, activate CNS innate immune signaling pathways, and induce para-infectious autoimmunity, potentially contributing to the CNS complications associated with SARS-CoV-2 infection. Direct viral infection of the brain parenchyma causing encephalitis, possibly with concurrent neurovascular endotheliitis and CNS renin angiotensin system (RAS) dysregulation, is also reviewed.
Promoting the use of evidence in health policymaking in the ECOWAS region: the development and contextualization of an evidence-based policymaking guidance
Authors: Uneke Chigozie Jesse , Sombie Issiaka , Johnson Ermel , Uneke Bilikis Iyabo , Okolo Stanley
Published: August 2020

Background

The Economic Commission of the West African States (ECOWAS), through her specialised health Institution, the West African Health Organization (WAHO) is supporting Members States to improve health outcomes in West Africa. There is a global recognition that evidence-based health policies are vital towards achieving continued improvement in health outcomes. The need to have a tool that will provide systematic guide on the use of evidence in policymaking necessitated the production of the evidence-based policy-making (EBPM) Guidance.

Methods

Google search was performed to identify existing guidance on EBPM. Lessons were drawn from the review of identified guidance documents. Consultation, interaction and interviews were held with policymakers from the 15 West African countries during WAHO organized regional meetings in Senegal, Nigeria, and Burkina Faso. The purpose was to elicit their views on the strategies to promote the use of evidence in policymaking to be included in the EBPM Guidance. A regional Guidance Validation Meeting for West African policymakers was thereafter convened by WAHO to review findings from review of existing guidance documents and validate the EBPM Guidance.

Results

Out of the 250 publications screened, six publications fulfilled the study inclusion criteria and were reviewed. Among the important issues highlighted include: what evidence informed decision-making is; different types of research methods, designs and approaches, and how to judge the quality of research. The identified main target end users of the EBPM Guidance are policy/decision makers in the West African sub-region, at local, sub-national, national and regional levels. Among the key recommendations included in the EBPM Guidance include: properly defining/refining policy problem; reviewing contextual issues; initiating policy priority setting; considering political acceptability of policy; commissioning research; use of rapid response services, use of policy advisory/technical/steering committees; and use of policy briefs and policy dialogue.

Conclusion

The EBPM Guidance is one of the emerging tools that can enhance the understanding of evidence to policy process. The strategies to facilitate the use of evidence in policymaking outlined in the Guidance, can be adapted to local context, and incorporated validated approaches that can be used to promote evidence-to-policy-to-practice process in West Africa.
Breastfed 13 month-old infant of a mother with COVID-19 pneumonia: a case report
Authors: Yu Yuanyuan , Li Youjiang , Hu Yingying , Li Bin , Xu Jian
Published: August 2020

Background

In China, mothers with confirmed or suspected COVID-19 pneumonia are recommended to stop breastfeeding. However, the evidence to support this guidance is lacking. There have been relatively few cases reported about direct breastfeeding an infant by a mother with SARS-CoV-2 pneumonia. Therefore, it is necessary to assess the safety of breastfeeding and the possible protective effects of breast milk on infants.

Case presentation

This report analyzes the case of a mother who continued breastfeeding her 13 month-old child when both were diagnosed with confirmed COVID-19 pneumonia. We describe the clinical presentation, diagnosis, treatment, and outcome. The presence of SARS-CoV-2 nucleic acid was determined in maternal serum, breast milk, nasopharyngeal (NP) swabs and feces, and in infant serum, NP swabs and feces. IgM and IgG antibodies against SARS-CoV-2 were assessed in maternal serum and breast milk and in infant serum. SARS-CoV-2 nucleic acid was not detected in the breast milk, and antibodies against SARS-CoV-2 were detected in the mother’s serum and milk.

Conclusions

The present case further confirms that the possibility of mother-to-child transmission about SARS-CoV-2 via breast milk alone was very small, and breast milk is safe for direct feeding of infants.
Mid-term results of revision surgery using double-trabecular metal cups alone or combined with impaction bone grafting for complex acetabular defects
Authors: Zhang Xianghong , Li Zhihong , Wang Wanchun , Liu Tang , Peng Weiqiu
Published: August 2020

Background

Revision surgery for complex acetabular defects is still technically challenging. In this study, we discussed and compared the clinical and radiological outcomes of revision surgery between two methods using double-trabecular metal (TM) cups alone or combined with impacting bone grafting (IBG).

Methods

The records of 18 patients (18 hips) who underwent revision surgery using double-trabecular metal (double-TM) cups between 2008 and 2016 were retrospectively reviewed. All the patients were diagnosed with Paprosky III acetabular defects. The acetabular defects were reconstructed by double-TM cups alone or in combination with IBG. We used the modified Harris Hip Score (mHHS), University of California, Los Angeles (UCLA), and Short Form 36 (SF-36) to evaluate the clinical outcomes. Pelvis plain X-ray was used to assess hip center of rotation (COR), abduction angle and anteversion angle of acetabular cup, and incorporation of the bone graft to host bone.

Results

The median follow-up time was 61.0 (IQR 56.0 to 65.8) months. No patients underwent re-revision for loosening or any other reasons. Complications included 3 patients (16.7%) with early dislocation and 3 patients (16.7%) with delayed wound healing. The average mHHS and UCLA preoperatively were 44.1 ± 4.0 (range 35 to 50) and 2.6 ± 0.7 (range 2 to 4), respectively and at the last follow-up were 73.7 ± 4.2 (range 68 to 85) and 7.3 ± 0.5 (range 7 to 8), respectively. The mean SF-36 scores at the last follow-up were improved significantly than preoperative scores, especially in bodily pain category (P < 0.05). The average limb-length discrepancy (LLD) decreased significantly from 24.2 ± 2.6 (range 20 to 32) mm preoperatively to 5.8 ± 1.8 (range 3 to 9) mm at the last follow-up, respectively. However, there was no significant difference between two methods at the last follow-up in terms of mHHS, UCLA, SF-36, LLD, and hip COR (P > 0.05). Radiographic evaluation demonstrated bone graft incorporation in all hips in the follow-up.

Conclusions

Defect reconstruction using double-TM cups alone or combined with IBG are practical and reliable treatment options for Paprosky III acetabular defects without pelvic discontinuity. Nevertheless, high postoperative complication rate, especially in terms of dislocation, remains a challenge.
The functional epigenetic landscape of aberrant gene expression in molecular subgroups of newly diagnosed multiple myeloma
Authors: Choudhury Samrat Roy , Ashby Cody , Tytarenko Ruslana , Bauer Michael , Wang Yan , Deshpande Shayu , Den Judith , Schinke Carolina , Zangari Maurizio , Thanendrarajan Sharmilan , Davies Faith E. , van Rhee Frits , Morgan Gareth J. , Walker Brian A.
Published: August 2020

Background

Multiple Myeloma (MM) is a hematological malignancy with genomic heterogeneity and poor survival outcome. Apart from the central role of genetic lesions, epigenetic anomalies have been identified as drivers in the development of the disease.

Methods

Alterations in the DNA methylome were mapped in 52 newly diagnosed MM (NDMM) patients of six molecular subgroups and matched with loci-specific chromatin marks to define their impact on gene expression. Differential DNA methylation analysis was performed using DMAP with a ≥10% increase (hypermethylation) or decrease (hypomethylation) in NDMM subgroups, compared to control samples, considered significant for all the subsequent analyses with p<0.05 after adjusting for a false discovery rate.

Results

We identified differentially methylated regions (DMRs) within the etiological cytogenetic subgroups of myeloma, compared to control plasma cells. Using gene expression data we identified genes that are dysregulated and correlate with DNA methylation levels, indicating a role for DNA methylation in their transcriptional control. We demonstrated that 70% of DMRs in the MM epigenome were hypomethylated and overlapped with repressive H3K27me3. In contrast, differentially expressed genes containing hypermethylated DMRs within the gene body or hypomethylated DMRs at the promoters overlapped with H3K4me1, H3K4me3, or H3K36me3 marks. Additionally, enrichment of BRD4 or MED1 at the H3K27ac enriched DMRs functioned as super-enhancers (SE), controlling the overexpression of genes or gene-cassettes.

Conclusions

Therefore, this study presents the underlying epigenetic regulatory networks of gene expression dysregulation in NDMM patients and identifies potential targets for future therapies.
Hospitalization for acute cerebellitis in children affected by varicella: how much does it cost?
Authors: Bozzola Elena , Guolo Stefano , Macchiarulo Giulia , Festa Lidia , Spina Giulia , Krzysztofiak Andrzej , Grandin Annalisa , Bozzola Mauro , Raponi Massimiliano , Villani Alberto
Published: August 2020

Background

Chickenpox is a highly contagious airborne disease caused by the varicella zoster virus. It is generally benign and self-limiting, but it may be responsible of life-threatening complications. Acute cerebellitis (AC) is the most common neurological complication and is associated with prolonged hospitalization in the acute phase (HAP).

Aim of the study

To estimate the costs of AC HAP in children affected by varicella.

Materials and methods

We retrospectively reviewed the medical records of a pediatric cohort hospitalized for chickenpox AC over a period of 15 years (from October 2003 to October 2018) and we analyzed acute care costs. For any patient the HAP has been calculated. The final value includes cost of hospital accommodation and management at the Pediatric and Infectious Diseases Unit. To this cost, the price of procedures (imaging, laboratory exams, medical and paramedical evaluations) and medical treatments was added.

Results

In the study period, 856 children had been hospitalized for varicella. Out of them, 65 met a diagnosis of AC and were included in the study. The hospitalization length was of 10 days (range 3–20 days). The median cost of HAP for each patient was of 5366 euro, with an average annual cost of 23,252 €. The most significant part of HAP is due to the cost of hospital accommodation and management at the Pediatric Infectious Diseases Unit, which was about € 537.78 for a single day.

Discussion

Although AC post-varicella is rare, its HAP cost is not negligible resulting in substantial economic burden. Vaccination would have probably prevented varicella and AC complication, avoiding hospitalization.

Conclusions

Financial studies are important for evaluate the cost saving in order to influence public funding decisions. Further studies are necessary to investigate the economic burden of the disease.
High-flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary disease patients after extubation: a multicenter, randomized controlled trial
Authors: Tan Dingyu , Walline Joseph Harold , Ling Bingyu , Xu Yan , Sun Jiayan , Wang Bingxia , Shan Xueqin , Wang Yunyun , Cao Peng , Zhu Qingcheng , Geng Ping , Xu Jun
Published: August 2020

Background

High-flow nasal cannula (HFNC) oxygen therapy is being increasingly used to prevent post-extubation hypoxemic respiratory failure and reintubation. However, evidence to support the use of HFNC in chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure after extubation is limited. This study was conducted to test if HFNC is non-inferior to non-invasive ventilation (NIV) in preventing post-extubation treatment failure in COPD patients previously intubated for hypercapnic respiratory failure.

Methods

COPD patients with hypercapnic respiratory failure who were already receiving invasive ventilation were randomized to HFNC or NIV at extubation at two large tertiary academic teaching hospitals. The primary endpoint was treatment failure, defined as either resumption of invasive ventilation or switching to the other study treatment modality (NIV for patients in the NFNC group or vice versa).

Results

Ninety-six patients were randomly assigned to the HFNC group or NIV group. After secondary exclusion, 44 patients in the HFNC group and 42 patients in the NIV group were included in the analysis. The treatment failure rate in the HFNC group was 22.7% and 28.6% in the NIV group—risk difference of − 5.8% (95% CI, − 23.8–12.4%,p = 0.535), which was significantly lower than the non-inferior margin of 9%. Analysis of the causes of treatment failure showed that treatment intolerance in the HFNC group was significantly lower than that in the NIV group, with a risk difference of − 50.0% (95% CI, − 74.6 to − 12.9%,p = 0.015). One hour after extubation, the mean respiratory rates of both groups were faster than their baseline levels before extubation (p < 0.050). Twenty-four hours after extubation, the respiratory rate of the HFNC group had returned to baseline, but the NIV group was still higher than the baseline. Forty-eight hours after extubation, the respiratory rates of both groups were not significantly different from the baseline. The average number of daily airway care interventions in the NIV group was 7 (5–9.3), which was significantly higher than 6 (4–7) times in the HFNC group (p = 0.006). The comfort score and incidence of nasal and facial skin breakdown of the HFNC group was also significantly better than that of the NIV group [7 (6–8) vs 5 (4–7),P < 0.001] and [0 vs 9.6%,p = 0.027], respectively.

Conclusion

Among COPD patients with severe hypercapnic respiratory failure who received invasive ventilation, the use of HFNC after extubation did not result in increased rates of treatment failure compared with NIV. HFNC also had better tolerance and comfort than NIV.

Trial registration

chictr.org(ChiCTR1800018530). Registered on 22 September 2018,http://www.chictr.org.cn/usercenter.aspx