bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of an obstetric early warning system model for use in low resource settings
Authors: Umar Aminu , Manu Alexander , Mathai Matthews , Ameh Charles
Published: September 2020

Background

The use of obstetric early-warning-systems (EWS) has been recommended to improve timely recognition, management and early referral of women who have or are developing a critical illness. Development of such prediction models should involve a statistical combination of predictor clinical observations into a multivariable model which should be validated. No obstetric EWS has been developed and validated for low resource settings. We report on the development and validation of a simple prediction model for obstetric morbidity and mortality in resource-limited settings.

Methods

We performed a multivariate logistic regression analysis using a retrospective case-control analysis of secondary data with clinical indices predictive of severe maternal outcome (SMO). Cases for design and validation were randomly selected (n = 500) from 4360 women diagnosed with SMO in 42 Nigerian tertiary-hospitals between June 2012 and mid-August 2013. Controls were 1000 obstetric admissions without SMO diagnosis. We used clinical observations collected within 24 h of SMO occurrence for cases, and normal births for controls. We created a combined dataset with two controls per case, split randomly into development (n = 600) and validation (n = 900) datasets. We assessed the model’s validity using sensitivity and specificity measures and its overall performance in predicting SMO using receiver operator characteristic (ROC) curves. We then fitted the final developmental model on the validation dataset and assessed its performance. Using the reference range proposed in the United Kingdom Confidential-Enquiry-into-Maternal-and-Child-Health 2007-report, we converted the model into a simple score-based obstetric EWS algorithm.

Results

The final developmental model comprised abnormal systolic blood pressure-(SBP > 140 mmHg or < 90 mmHg), high diastolic blood pressure-(DBP > 90 mmHg), respiratory rate-(RR > 40/min), temperature-(> 38 °C), pulse rate-(PR > 120/min), caesarean-birth, and the number of previous caesarean-births. The model was 86% (95% CI 81–90) sensitive and 92%- (95% CI 89–94) specific in predicting SMO with area under ROC of 92% (95% CI 90–95%). All parameters were significant in the validation model except DBP. The model maintained good discriminatory power in the validation (n = 900) dataset (AUC 92, 95% CI 88–94%) and had good screening characteristics. Low urine output (300mls/24 h) and conscious level (prolonged unconsciousness-GCS < 8/15) were strong predictors of SMO in the univariate analysis.

Conclusion

We developed and validated statistical models that performed well in predicting SMO using data from a low resource settings. Based on these, we proposed a simple score based obstetric EWS algorithm with RR, temperature, systolic BP, pulse rate, consciousness level, urinary output and mode of birth that has a potential for clinical use in low-resource settings..
Clinical characteristics and outcome of pediatric patients diagnosed with Langerhans cell histiocytosis in pediatric hematology and oncology centers in Poland
Authors: Raciborska Anna , Bilska Katarzyna , Węcławek-Tompol Jadwiga , Gryniewicz-Kwiatkowska Olga , Hnatko-Kołacz Małgorzata , Stefanowicz Joanna , Pieczonka Anna , Jankowska Katarzyna , Pierelejewski Filip , Ociepa Tomasz , Sobol-Milejska Grażyna , Muszyńska-Rosłan Katarzyna , Michoń Olga , Badowska Wanda , Radwańska Monika , Drabko Katarzyna
Published: September 2020

Background

Langerhans cell histiocytosis (LCH) affects 1–2 in 1,000,000 people. The disease is not associated with increased risk of treatment failure (especially among older children), but appropriate procedures implemented in advance can eliminate complications which might appear and significantly worsen the patients’ quality of life. Thus, we sought to evaluate the clinical features, management, and outcome of children with LCH treated in Polish pediatric hematology-oncology centers.

Materials and methods

One hundred eighty two patients with LCH were treated according to the Histiocytic Society Guidelines between 2010 and 2017. The participating centers were requested to provide the following data: demographic, clinical, as well as local or systemic treatment data and patients’ outcome. Overall survival (OS) and event free survival (EFS) were estimated by Kaplan-Meier methods and compared using the log-rank test.

Results

Sixty nine percent of children were classified as single system (SS). The patients with SS disease were significantly older as compared to the children with multisystem disease (MS), 6 vs. 2.3 years respectively (p 0.003). Bones were involved in 76% of patients. Systemic treatment was applied to 47% of children with SS disease and 98% with MS disease. Fourteen patients relapsed while two children died. OS and EFS in entire group were 0.99 and 0.91 respectively (with median follow-up 4.3 years).

Conclusion

The treatment of LCH in Polish centers was effective, however, new approaches, including mutation analyses and good inter-center cooperation, are needed to identify patients who might require modification or intensification of treatment.
The global impact of Aspergillus infection on COPD
Authors: Hammond Emily E. , McDonald Charles S. , Vestbo Jørgen , Denning David W.
Published: September 2020

Background

Advanced chronic obstructive pulmonary disease (COPD) often leads to hospitalisation and invasive aspergillosis (IA) is a serious complication. Aspergillus sensitisation may worsen symptoms in COPD.

Methods

We identified published papers between January 2000 and May 2019 with > 50 subjects and GOLD criteria for grade II, III or IV (FEV1/FVC < 70% and FEV1 < 80%) using standardised criteria in multiple countries, to re-estimate the prevalence of COPD. Hospitalised COPD patients develop IA in 1.3–3.9%, based on positive cultures of Aspergillus spp. and radiological findings. Given limited data on per-patient annual hospitalisation rates, we assumed a conservative 10.5% estimate. Annual IA mortality in COPD was estimated using the literature rates of 43–72%. A separate literature search assessed the impact of Aspergillus sensitisation on severity of COPD (by FEV1).

Results

We re-estimated the global prevalence of COPD GOLD stages II-IV at 552,300,599 people (7.39% of the population) with 339,206,893 (8.58%) in Asia, 85,278,783 (8.52%) in the Americas, 64,298,051 (5.37%) in Africa, 59,484,329 (7.77%) in Europe and 4,032,543 (10.86%) in Oceania. An estimated 57,991,563 (10.5%) people with COPD are admitted to hospital annually and of these 753,073 (1.3%) – 2,272,322 (3.9%) develop IA and 540,451–977,082 deaths are predicted annually. Aspergillus sensitisation prevalence in COPD was 13.6% (7.0–18.3%) and not related to lower predicted FEV1% (P > 0.05).

Conclusions

The prevalence of COPD is much higher than previously estimated. Overall COPD mortality may be higher than estimated and IA probably contributes to many deaths. Improved rapid diagnosis of IA using culture and non-culture based techniques is required in COPD hospital admissions to reduce mortality.
Safety of bronchoscopy in patients with malignant hematologic disorders
Authors: Uruga Hironori , Sato Toshitaka , Nishida Aya , Uchida Naoyuki , Tsuji Masanori , Moriguchi Shuhei , Takahashi Yui , Ogawa Kazumasa , Murase Kyoko , Hanada Shigeo , Takaya Hisashi , Miyamoto Atsushi , Morokawa Nasa , Kimura Muneyoshi , Araoka Hideki , Tsuchihashi Rumiko , Asano-Mori Yuki , Wake Atsushi , Taniguchi Shuichi , Kishi Kazuma
Published: September 2020

Background

Factors affecting the safety of bronchoscopy in patients with malignant hematologic disorders have not been well described. We evaluated the safety of bronchoscopy and describe factors affecting its complication rate in such patients.

Methods

Between January 2009 and December 2018, 316 bronchoscopies in 282 patients with malignant hematologic disorders and pulmonary infiltrates were performed at our institution. The bronchoscopic procedure used and its complications were evaluated.

Results

The most common underlying disease was acute myeloid leukemia (134/282 patients, 47.5%). Platelet transfusion was performed the day before or the day of bronchoscopy in 42.4%, supplemental oxygen was administered before the procedure in 23.1%, and midazolam was used in 74.4%. Thirty-five bronchoscopies (11.1%) were complicated by hemoptysis and 7 patients developed pneumothorax, 4 of whom required thoracic drainage. Two patients (0.6%) were intubated within 48 h of the procedure and prolonged oxygen desaturation (> 48 h) occurred in 3.8%. Multivariate analysis showed that only use of midazolam significantly reduced the risk of prolonged oxygen desaturation (hazard ratio 0.28, 95% confidence interval 0.09–0.85, p = 0.03). Transbronchial lung biopsy significantly increased the risk of hemoptysis (hazard ratio 10.40, 95% confidence interval 4.18–25.90, p = 0.00), while use of midazolam significantly reduced the risk (hazard ratio 0.31, 95% confidence interval 0.14–0.73, p = 0.01).

Conclusions

Bronchoscopy is relatively safe in patients with malignant hematologic disorders. Caution and judicious use of sedatives may improve the patient’s procedural tolerance and lower complications.
Quercetin reduces tendon adhesion in rat through suppression of oxidative stress
Authors: Liang Yuan , Xu Keteng , Zhang Pei , Zhang Jiale , Chen Pengtao , He Jinshan , Fang Yongchao , Zhou Yuelai , Wang Jingcheng , Bai Jianzhong
Published: September 2020

Background

Tendon adhesion is one of the most common clinical problems, which poses a considerable challenge to orthopedics doctors. Quercetin (QUE) as a popular drug at present, it has various biological functions, including anti-inflammatory, anti-ischemic, anti-peroxidation, and antioxidant. The purpose of this study was to investigate the effect of quercetin on tendon adhesion and whether quercetin can inhibit oxidative stress.

Method

Thirty-six rats were randomly divided into three groups, including control group, low QUE (50 mg/kg/day) group, and high QUE (100 mg/kg/day) group. After 1 week, the levels of SOD, MDA and GPx were measured. The degree of tendon adhesion was assessed by macroscopic evaluation and histological evaluation. After 4 weeks. Besides, the pharmacological toxicity of quercetin to main organs were evaluated by histological analysis.

Results

The extent of superoxide dismutase (SOD) and glutathione peroxidase (GPx) of tendon tissue in high QUE group was significantly higher than those of low QUE group and control group. And the extent of malondialdehyde (MDA) of tendon tissue in high QUE group was significantly lower than that of low QUE group and control group. By macroscopic evaluation and histological analysis, the extent of tendon adhesion in high QUE group was lower than low QUE group and control group. However, there were no significant changes of the major organs through histological analysis.

Conclusions

Quercetin may be a good and safe strategy in preventing tendon adhesion. But further clinical research is needed before its recommendation in the prevention and treatment of tendon adhesion.
Stagewise resolution of temperature-dependent embryonic and postembryonic development in the cowpea seed beetle Callosobruchus maculatus (F.)
Authors: Kutcherov Dmitry
Published: September 2020

Background

The thermal plasticity of life-history traits receives wide attention in the recent biological literature. Of all the temperature-dependent traits studied, developmental rates of ectotherms are especially often addressed, and yet surprisingly little is known about embryonic responses to temperature, including changes in the thermal thresholds and thermal sensitivity during early development. Even postembryonic development of many cryptically living species is understood superficially at best.

Results

This study is the first to estimate the exact durations of developmental stages in the cowpea seed beetle C. maculatus from oviposition to adult emergence at five permissive constant temperatures from 20 to 32 °C. Early embryonic development was tracked and documented by means of destructive sampling and subsequent confocal imaging of fluorescently stained specimens. Late embryonic and early larval development was studied with the use of destructive sampling and light microscopy. Well-resolved temporal series based on thousands of embryos allowed precise timing of the following developmental events: formation of the blastoderm; formation, elongation, and retraction of the germ band; dorsal closure; the onset and completion of sclerotization of the cuticle; hatching, and penetration of the first-instar larva into the cowpea seed. Pupation and adult eclosion were observed directly through an incision in the seed coat. The thermal phenotype of C. maculatus was found to vary in the course of ontogeny and different stages scaled disproportionately with temperature, but pitfalls and caveats associated with analyses of relative durations of individual stages are also briefly discussed.

Conclusion

Disproportionate changes in developmental durations with temperature may have important implications when study design requires a high degree of synchronization among experimental embryos or when the occurrence of particular stages in the field is of interest, as well as in any other cases when development times need to be estimated with precision. This work provides one of the first examples of integration of embryological techniques with ecophysiological concepts and will hopefully motivate similar projects in the future. While experiments with Drosophila continue to be the main source of information on animal development, knowledge on other model species is instrumental to building a broader picture of developmental phenomena.
Study of laboratory staff’ knowledge of biobanking in Côte d’Ivoire
Authors: Kintossou Ambroise Kouamé , N’dri Mathias Kouamé , Money Marcelle , Cissé Souleymane , Doumbia Simini , Soumahoro Man-Koumba , Coulibaly Amadou Founzégué , Djaman Joseph Allico , Dosso Mireille
Published: September 2020

Background

A biobank is a structure which collects and manages biological samples and their associated data. The collected samples will then be made available for various uses. The sharing of those samples raised ethical questions which have been answered through specific rules. Thus, a Biobank functioning under tight ethical rules would be immensely valuable from a scientific and an economic view point. In 2009, Côte d’Ivoire established a biobank, which has been chosen to house the regional biobank of Economic Community of West African States (ECOWAS) countries in 2018. To ensure optimal and efficient use of this biobank, the scientific community must be aware of its existence and its role. It was therefore necessary to evaluate the knowledge of laboratories staff on the role and activities of a biobank.

Methods

This descriptive study was done by questioning staff from laboratories working on human’s health, animals or plants. The laboratories were located in southern Côte d’Ivoire.

Results

A total of 205 people completed the questionnaire. Of these 205 people, 34.63% were biologists, 7.32% engineers, 48.78% technicians and 9.27% PhD students. The average length of work experience was 10.11 ± 7.83 years. In this study, 43.41% of the participants had never heard of biobanking. Only 48.78% of participants had a good understanding of the role of a biobank. Technicians and PhD students were less educated on the notion of biobank (p < 0.000001). Although biologists were more educated on this issue, 21.13% of them had a misconception of biobank. Good knowledge of the role of a biobank was not significantly related to the work experience’s length (p > 0.88).

Conclusion

The level of knowledge of laboratory staff about biobanking needs to be improved. Training on the role, activities and interests of the biobank is important.
Implementation of three innovative interventions in a psychiatric emergency department aimed at improving service use: a mixed-method study
Authors: Gabet Morgane , Grenier Guy , Cao Zhirong , Fleury Marie-Josée
Published: September 2020

Background

Emergency department (ED) use is often viewed as an indicator of health system quality. ED use for mental health (MH) reasons is increasing and costly for health systems, patients, and their families. Patients with mental disorders (MD) including substance use disorders (SUD) and suicidal behaviors are high ED users. Improving ED services for these patients and their families, and developing alternatives to ED use are thus key issues. This study aimed to: (1) describe the implementation of three innovative interventions provided by a brief intervention team, crisis center team, and family-peer support team in a Quebec psychiatric ED, including the identification of implementation barriers, and (2) evaluate the impacts of these ED innovations on MH service use and response to needs.

Method

Using mixed methods with data triangulation, the implementation and impact of the three above-named ED interventions were studied. Quantitative data were collected from 101 participants (81 patients, 20 family members) using a user questionnaire and patient medical records. Qualitative data were gathered from focus groups (n = 3) with key intervention staff members (n = 14). The user questionnaire also included open-ended questions. Descriptive, comparative and content analyses were produced.

Results

Key implementation issues were identified in relation to system, organizational and patient profiles, similar to results identified in most studies in the ED implementation literature aimed at improving responsiveness to patients with MD. Results were encouraging, as the innovations had a significant impact for improved patient MH service use and adequacy of care. Services also seemed adapted to patient profiles. Family members were grateful for the help received in the ED.

Conclusions

Before implementing innovations, managers need to recognize the basic issues common to all new healthcare interventions: the need for staff training and strong involvement, particularly among physicians, development of collaborative tools especially in cases of potential cultural clash between staff and organizations, and continuous quality assessment. Future research needs to confirm the pertinence of these interventions, especially use of family-peer support teams in ED, as a highly innovative intervention. Broader ED strategies could also be deployed to improve MH services and decrease ED use for MH reasons.
(Dis)concordance of comorbidity data and cancer status across administrative datasets, medical charts, and self-reports
Authors: Sheriffdeen A. , Millar J. L. , Martin C. , Evans M. , Tikellis G. , Evans S. M.
Published: September 2020

Background

Benchmarking outcomes across settings commonly requires risk-adjustment for co-morbidities that must be derived from extant sources that were designed for other purposes. A question arises as to the extent to which differing available sources for health data will be concordant when inferring the type and severity of co-morbidities, how close are these to the “truth”. We studied the level of concordance for same-patient comorbidity data extracted from administrative data (coded from International Classification of Diseases, Australian modification,10th edition [ICD-10 AM]), from the medical chart audit, and data self-reported by men with prostate cancer who had undergone a radical prostatectomy.

Methods

We included six hospitals (5 public and 1 private) contributing to the Prostate Cancer Outcomes Registry-Victoria (PCOR-Vic) in the study. Eligible patients from the PCOR-Vic underwent a radical prostatectomy between January 2017 and April 2018.Health Information Manager’s in each hospital, provided each patient’s associated administrative ICD-10 AM comorbidity codes. Medical charts were reviewed to extract comorbidity data. The self-reported comorbidity questionnaire (SCQ) was distributed through PCOR-Vic to eligible men.

Results

The percentage agreement between the administrative data, medical charts and self-reports ranged from 92 to 99% in the 122 patients from the 217 eligible participants who responded to the questionnaire. The presence of comorbidities showed a poor level of agreement between data sources.

Conclusion

Relying on a single data source to generate comorbidity indices for risk-modelling purposes may fail to capture the reality of a patient’s disease profile. There does not appear to be a ‘gold-standard’ data source for the collection of data on comorbidities.
Down-regulation of lncRNA UCA1 enhances radiosensitivity in prostate cancer by suppressing EIF4G1 expression via sponging miR-331-3p
Authors: Hu Minhua , Yang Jincheng
Published: September 2020

Background

We aimed to explore the role of long noncoding RNA urothelial carcinoma-associated 1 (lncRNA UCA1) and its underlying mechanism in the radioresistance of prostate cancer (PCa).

Methods

QRT-PCR was conducted to measure the expression of UCA1, microRNA-331-3p (miR-331-3p) and eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in PCa tissues and cells. The relative protein level was determined by western blot assay. Cell proliferation and apoptosis were detected by MTT, colony formation assay, and flow cytometry, respectively. The target interaction between miR-331-3p and UCA1 or EIF4G1 was predicted through bioinformatics analysis, and verified by dual-luciferase reporter gene assay system.

Results

The high levels of UCA1 and EIF4G1 as well as the low level of miR-331-3p were observed in PCa tissues and cell lines. UCA1 and EIF4G1 expression were significantly upregulated by Gy radiation treatement. UCA1 or EIF4G1 knockdown repressed cell growth and enhanced cell apoptosis in 22RV1 and DU145 cells under radiation. Moreover, overexpression of EIF4G1 abolished UCA1 knockdown-induced effect on 6 Gy irradiated PCa cells. UCA1 sponged miR-331-3p to regulate EIF4G1 expression.

Conclusions

LncRNA UCA1 deletion suppressed the radioresistance to PCa by suppressing EIF4G1 expression via miR-331-3p. UCA1 acted as a potential regulator of radioresistance of PCa, providing a promising therapeutic target for PCa.
Important considerations when assessing the effect of essential fatty acids on cognitive performance
Authors: Visaria Aayush , Lo David , Maniar Pranay
Published: September 2020

Over the past decade, there have been many studies determining the effect of dietary ω-3 and ω-6 fatty acids intake on cognitive performance; however, they have largely been inconsistent in their conclusions. In this letter, we provide context to the article by Dong et al., titled “Association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in older adults: National Health and nutrition examination Survey (NHANES) 2011–2014” and provide methodological considerations with regards to covariate measurement and inclusion that can be generalized to future cross-sectional studies. In particular, delineating 1) the type and source of fatty acid, in context of an individual’s overall dietary patterns, 2) sociobehavioral risk factors and physical & mental comorbidities, 3) and daily cognitive activity are important to adequately control for covariates.
Adults’ leisure-time physical activity and the neighborhood built environment: a contextual perspective
Authors: Kajosaari Anna , Laatikainen Tiina E.
Published: September 2020

Background

Context-free outcome measures, such as overall leisure-time physical activity (LTPA), are habitually applied to study the neighborhood built environment correlates of physical activity. This cross sectional study identifies and empirically tests potential methodological limitations related to the use of context-free measures and discusses how these may help in the interpretation of inconsistent associations between participation in moderate-to-vigorous LTPA and objectively measured neighborhood-level built environment attributes.

Methods

We employ a public participation geographic information system (PPGIS), an advanced participatory mapping method, to study the spatial distribution of moderate-to-vigorous LTPA among adult urban Finnish residents (n1322). Secondary sources of GIS land-use and sport facility data were used to disaggregate respondent-mapped LTPA by the behavioral context, such as indoor and outdoor sport facilities, green spaces, and other public open spaces. Associations between the use of the identified LTPA settings and a range of objectively measured neighborhood built environment attributes were studied with multilevel logistic regression models.

Results

Disaggregated by behavioral context, we observed varied and partly opposite built environment correlates for LTPA. The use of indoor and outdoor sport facilities showed no significant associations with their neighborhood availability, but were significantly associated with personal-level attributes. By contrast, participation in LTPA in green and built public open space shared significant associations with access to and availability of neighborhood green space that persisted after controlling for personal-level covariates. Moreover, neighborhood distances up to 1600 m poorly captured participation in moderate-to-vigorous LTPA, as, on average, 40% of visits were located further from home. However, we found the immediate home environment to be an important LTPA setting for the least active participants.

Conclusions

This study demonstrates that LTPA can be a highly heterogeneous measure regarding both the spatial distribution and the environmental correlates of behavioral contexts. The results show that context-free LTPA outcome measures yield inconsistent associations with built environment exposure variables, challenging the applicability of such measures in designing neighborhood-level built environment interventions.
Identification of factors influencing tampering of codeine-containing medicines in England: a qualitative study
Authors: Kimergård Andreas , Parkin Stephen , Jennings Stacey , Brobbin Eileen , Deluca Paolo
Published: September 2020

Background

Tampering of psychoactive medicines presents challenges to regulation and public health. However, little is currently known about what influences the decisions to treat codeine-containing medicines (CCM) with cold water extraction (CWE) from the perspective of individuals employing these techniques. The article identifies factors influencing utilisation of CWE to separate codeine from compounded analgesics, such as paracetamol and ibuprofen, found in CCM.

Methods

Purposive sampling of 27 participants residing in England who took part in a qualitative interview. Of these, 14 individuals (11 males and 3 females) reported tampering of psychoactive medicines, and the relevant transcripts were included in the analyses for the study. Participants were recruited from one addiction treatment service and from an online survey. The mean age of the participants was 31.5 years (range = 18–42 years). Qualitative data analysis followed the processes of iterative categorization (IC). The codes ‘harm reduction’, ‘information sources’ and ‘changes on the drug markets’ were grouped and summarised. The coding of the data was done in a Microsoft® Word document.

Results

Two groups of participants were identified in the data analysis: (i) individuals who used CCM (n = 5), and (ii) individuals who used CCM and heroin (n = 9). Participants in both groups used CWE due to concerns of paracetamol overdose from the use of excessive dosages of CCM. For both of them, information obtained from the internet encouraged the use of CWE. Participants using CCM described how the many steps involved in conducting CWE, including sourcing codeine boxes from pharmacies (over the counter), presented a barrier against using CWE. Participants using CCM and heroin explained how reduced availability in the local heroin supply influenced utilisation of CWE techniques to maintain their use of opioids and avoid withdrawal. Withdrawal symptoms and cravings outweighed the concerns about the quality of the extracted codeine mixtures in this participant group, especially the ability of CWE to remove paracetamol and tablet fillers.

Conclusions

Utilisation of CWE of codeine was influenced by several factors including drug market supply, the availability of detailed information on the internet about CWE and restrictions on codeine sourcing in pharmacies. Risks identified with CWE include consumption of unknown doses of paracetamol if the CWE techniques are not used correctly. Attempts at extracting codeine from CCM should be considered in risk assessments of opioid medicines.
Cost-effectiveness of facility-based, stand-alone and mobile-based voluntary counseling and testing for HIV in Addis Ababa, Ethiopia
Authors: Yigezu Amanuel , Alemayehu Senait , Hamusse Shallo Daba , Ergeta Getachew Teshome , Hailemariam Damen , Hailu Alemayehu
Published: September 2020

Background

Globally, there is a consensus to end the HIV/AIDS epidemic by 2030, and one of the strategies to achieve this target is that 90% of people living with HIV should know their HIV status. Even if there is strong evidence of clients’ preference for testing in the community, HIV voluntary counseling and testing (VCT) continue to be undertaken predominantly in health facilities. Hence, empirical cost-effectiveness evidence about different HIV counseling and testing models is essential to inform whether such community-based testing are justifiable compared with additional resources required. Therefore, the purpose of this study was to compare the cost-effectiveness of facility-based, stand-alone and mobile-based HIV voluntary counseling and testing methods in Addis Ababa, Ethiopia.

Methods

Annual economic costs of counseling and testing methods were collected from the providers’ perspective from July 2016 to June 2017. Ingredients based bottom-up costing approach was applied. The effectiveness of the interventions was measured in terms of the number of HIV seropositive clients identified. Decision tree modeling was built using TreeAge Pro 2018 software, and one-way and probabilistic sensitivity analyses were conducted by varying HIV positivity rate, costs, and probabilities.

Results

The cost of test per client for facility-based, stand-alone and mobile-based VCT was $5.06, $6.55 and $3.35, respectively. The unit costs of test per HIV seropositive client for the corresponding models were $158.82, $150.97 and $135.82, respectively. Of the three models, stand-alone-based VCT was extendedly dominated. Mobile-based VCT costs, an additional cost of USD 239 for every HIV positive client identified when compared to facility-based VCT.

Conclusion

Using a mobile-based VCT approach costs less than both the facility-based and stand-alone approaches, in terms of both unit cost per tested individual and unit cost per HIV seropositive cases identified. The stand-alone VCT approach was not cost-effective compared to facility-based and mobile-based VCT. The incremental cost-effectiveness ratio for mobile-based VCT compared with facility-based VCT was USD 239 per HIV positive case.
Exosomal microRNAs derived from mesenchymal stem cells: cell-to-cell messages
Authors: Asgarpour Kasra , Shojaei Zahra , Amiri Fatemeh , Ai Jafar , Mahjoubin-Tehran Maryam , Ghasemi Faezeh , ArefNezhad Reza , Hamblin Michael R. , Mirzaei Hamed
Published: September 2020

Exosomes are extracellular vesicles characterized by their size, source, release mechanism and contents. MicroRNAs (miRNAs) are single stranded non-coding RNAs transcribed from DNA. Exosomes and miRNAs are widespread in eukaryotic cells, especially in mesenchymal stem cells (MSCs). MSCs are used for tissue regeneration, and also exert paracrine, anti-inflammatory and immunomodulatory effects. However, the use of MSCs is controversial, especially in the presence or after the remission of a tumor, due to their secretion of growth factors and their migration ability. Instead of intact MSCs, MSC-derived compartments or substances could be used as practical tools for diagnosis, follow up, management and monitoring of diseases. Herein, we discuss some aspects of exosomal miRNAs derived from MSCs in the progression, diagnosis and treatment of various diseases.
Establishing an international awareness day for paediatric rheumatic diseases: reflections from the inaugural World Young Rheumatic Diseases (WORD) Day 2019
Authors: Smith Eve M. D. , Ainsworth Sammy , Beresford Michael W. , Buys Veerle , Costello Wendy , Egert Yona , Foster Helen E. , Lamot Lovro , Prakken Berent J. , Scott Christiaan , Stones Simon R.
Published: September 2020

There is a lack of awareness of paediatric rheumatic diseases (PRDs), among the public, and certain groups of healthcare professionals (HCPs), including general practitioners. To help improve international awareness and understanding of PRDs, World yOung Rheumatic Diseases (WORD) Day was established on 18 March 2019. Its aim was to raise awareness of PRDs and the importance of timely referral plus early diagnosis and access to appropriate treatment and support. A steering committee was established, and an external agency provided digital support. A social media campaign was launched in December 2018 to promote it, and analytics were used to measure its impact. Face-to-face and virtual events took place globally on or around WORD Day 2019, with 34 countries reporting events. Examples included lectures, social gatherings and media appearances. A total of 2585 and 660 individuals followed the official Facebook and Twitter accounts respectively, up until WORD Day. The official #WORDDay2019 hashtag was seen by 533,955 unique accounts on 18 March 2019 alone, with 3.3 million impressions. WORD Day 2019 was the first international campaign focused solely on PRDs. It demonstrated that despite awareness events being often resource-light, they can be implemented across a range of diverse settings. WORD Day has now become an annual global awareness event, facilitated by a growing network of patient, parent and professional community supporters.
A case of Myhre syndrome mimicking juvenile scleroderma
Authors: Jensen Barbara , James Rebecca , Hong Ying , Omoyinmi Ebun , Pilkington Clarissa , Sebire Neil J. , Howell Kevin J. , Brogan Paul A. , Eleftheriou Despina
Published: September 2020

Background

Myhre syndrome is a genetic disorder caused by gain of function mutations in the SMAD Family Member 4 (SMAD4) gene, resulting in progressive, proliferative skin and organ fibrosis. Skin thickening and joint contractures are often the main presenting features of the disease and may be mistaken for juvenile scleroderma.

Case presentation

We report a case of a 13 year-old female presenting with widespread skin thickening and joint contractures from infancy. She was diagnosed with diffuse cutaneous systemic sclerosis, and treatment with corticosteroids and subcutaneous methotrexate recommended. There was however disease progression prompting genetic testing. This identified a rare heterozygous pathogenic variant c.1499 T > C (p.Ile500Thr) in the SMAD4 gene, suggesting a diagnosis of Myhre syndrome. Securing a molecular diagnosis in this case allowed the cessation of immunosuppression, thus reducing the burden of unnecessary and potentially harmful treatment, and allowing genetic counselling.

Conclusion

Myhre Syndrome is a rare genetic mimic of scleroderma that should be considered alongside several other monogenic diseases presenting with pathological fibrosis from early in life. We highlight this case to provide an overview of these genetic mimics of scleroderma, and highlight the molecular pathways that can lead to pathological fibrosis. This may provide clues to the pathogenesis of sporadic juvenile scleroderma, and could suggest novel therapeutic targets.
Hippocampal interleukin-33 mediates neuroinflammation-induced cognitive impairments
Authors: Reverchon Flora , de Concini Vidian , Larrigaldie Vanessa , Benmerzoug Sulayman , Briault Sylvain , Togbé Dieudonnée , Ryffel Bernhard , Quesniaux Valérie F. J. , Menuet Arnaud
Published: September 2020

Background

Interleukin (IL)-33 is expressed in a healthy brain and plays a pivotal role in several neuropathologies, as protective or contributing to the development of cerebral diseases associated with cognitive impairments. However, the role of IL-33 in the brain is poorly understood, raising the question of its involvement in immunoregulatory mechanisms.

Methods

We administered recombinant IL-33 (rmIL-33) by intra-hippocampal injection to C57BL/6 J (WT) and IL-1αβ deficient mice. Chronic minocycline administration was performed and cognitive functions were examined trough spatial habituation test. Hippocampal inflammatory responses were investigated by RT-qPCR. The microglia activation was assessed using immunohistological staining and fluorescence-activated cell sorting (FACS).

Results

We showed that IL-33 administration in mice led to a spatial memory performance defect associated with an increase of inflammatory markers in the hippocampus while minocycline administration limited the inflammatory response. Quantitative assessment of glial cell activation in situ demonstrated an increase of proximal intersections per radius in each part of the hippocampus. Moreover, rmIL-33 significantly promoted the outgrowth of microglial processes. Fluorescence-activated cell sorting analysis on isolated microglia, revealed overexpression of IL-1β, 48 h post-rmIL-33 administration. This microglial reactivity was closely related to the onset of cognitive disturbance. Finally, we demonstrated that IL-1αβ deficient mice were resistant to cognitive disorders after intra-hippocampal IL-33 injection.

Conclusion

Thus, hippocampal IL-33 induced an inflammatory state, including IL-1β overexpression by microglia cells, being causative of the cognitive impairment. These results highlight the pathological role for IL-33 in the central nervous system, independently of a specific neuropathological model.
Cottonseed oil alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia and astrocyte
Authors: Liu Min , Xu Zhipeng , Wang Long , Zhang Lixia , Liu Yi , Cao Jiangbei , Fu Qiang , Liu Yanhong , Li Hao , Lou Jingsheng , Hou Wugang , Mi Weidong , Ma Yulong
Published: September 2020

Background

Ischemic stroke is the second leading cause of death globally. The narrow time window for administering effective thrombolytic therapy motivates the search for alternative prevention strategies. Microglia and astrocyte activation-mediated inflammation play a pivotal role in ischemic stroke injury. Cottonseed oil (CSO) has been shown to exert anti-inflammatory effects against peripheral tissue injury, although CSO is mostly used as a solvent for lipid-soluble drugs. However, the role of CSO in neuroprotection against stroke has not been previously reported.

Methods

We treated adult male rats with CSO (1.3 ml/kg, subcutaneous injection, once every other day for 3 weeks) and then constructed a middle cerebral artery occlusion (MCAO) model followed by 24 h of reperfusion. Then, we measured the neurological scores, infarction volume, neuronal injury, and brain edema; we also measured the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), degree of microglial and astrocytic activation, protein expression levels of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), C3d and S100A10, and the presence of A1 type astrocytes and A2 type astrocytes.

Results

We found that CSO treatment significantly improved the neurological deficit, reduced infarction volume, and alleviated neuronal injuries, blood–brain barrier (BBB) disruption, and brain edema. Additionally, CSO treatment significantly reduced microglial and astrocytic activation, inhibited TLR4 and NF-κB protein expression, and reduced the release of IL-1β, IL-6, and TNF-α. Finally, CSO treatment significantly decreased the number of C3d/glial fibrillary acidic protein (GFAP)-positive cells and C3d protein expression, and increased the number of S100A10/GFAP-positive cells and S100A10 protein expression.

Conclusion

Our results first found that CSO treatment alleviated ischemic stroke injury by reducing microglial and astrocytic activation and inflammation, which was related to the inhibition of TLR4/NF-κB pathway and the reduction of A1 phenotype neurotoxic astrocyte activation, suggesting that CSO could be a new strategy in the prevention of ischemic stroke.
Alpha-enolase in viral target cells suppresses the human immunodeficiency virus type 1 integration
Authors: Kishimoto Naoki , Yamamoto Kengo , Iga Nozomi , Kirihara Chie , Abe Towa , Takamune Nobutoki , Misumi Shogo
Published: September 2020

Background

A protein exhibiting more than one biochemical function is termed a moonlighting protein. Glycolytic enzymes are typical moonlighting proteins, and these enzymes control the infection of various viruses. Previously, we reported that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and alpha-enolase (ENO1) are incorporated into human immunodeficiency virus type 1 (HIV-1) particles from viral producer cells and suppress viral reverse transcription independently each other. However, it remains unclear whether these proteins expressed in viral target cells affect the early phase of HIV-1 replication.

Results

Here we show that the GAPDH expression level in viral target cells does not affect the early phase of HIV-1 replication, but ENO1 has a capacity to suppress viral integration in viral target cells. In contrast to GAPDH, suppression of ENO1 expression by RNA interference in the target cells increased viral infectivity, but had no effect on the expression levels of the HIV-1 receptors CD4, CCR5 and CXCR4 and on the level of HIV-1 entry. Quantitative analysis of HIV-1 reverse transcription products showed that the number of copies of the late products (R/gag) and two-long-terminal-repeat circular forms of viral cDNAs did not change but that of the integrated (Alu-gag) form increased. In contrast, overexpression of ENO1 in viral target cells decreased viral infectivity owing to the low viral integration efficiency. Results of subcellular fractionation experiments suggest that the HIV integration at the nucleus was negatively regulated by ENO1 localized in the nucleus. In addition, the overexpression of ENO1 in both viral producer cells and target cells most markedly suppressed the viral replication.

Conclusions

These results indicate that ENO1 in the viral target cells prevents HIV-1 integration. Importantly, ENO1, but not GAPDH, has the bifunctional inhibitory activity against HIV-1 replication. The results provide and new insights into the function of ENO1 as a moonlighting protein in HIV-1 infection.
Decision-making preferences and risk factors regarding early adolescent pregnancy in Ghana: stakeholders’ and adolescents’ perspectives from a vignette-based qualitative study
Authors: Bain Luchuo Engelbert , Muftugil-Yalcin Seda , Amoakoh-Coleman Mary , Zweekhorst Marjolein B. M. , Becquet Renaud , de Cock Buning Tjard
Published: September 2020

Background

Worldwide, over half of the adolescent pregnancies recorded are unintended. The decision to continue the pregnancy to term or to opt for an abortion is a constant dilemma that is directly or indirectly influenced by stakeholders and also by the wider social environment. This study aimed at understanding the perceived decision-making preferences and determinants of early adolescent pregnancy in the Jamestown area of Accra in Ghana.

Methods

A vignette-based qualitative study design was used. Eight focus group discussions were carried among various purposively selected groups of participants: parents, teachers, adolescent students who had not been pregnant before, and adolescents who had had at least one pregnancy in the past. The vignette was a hypothetical case of a 15-year-old high school student who had not experienced her menses for the past 6 weeks. The data were analyzed using a thematic analysis approach.

Results

Lack of parent-daughter communication, the taboo on discussing sex-related issues in households and weak financial autonomy were considered to be the main contributing factors to the high early adolescent pregnancy rates in the community. Partner readiness to assume responsibility for the girl and the baby was a key consideration in either continuing the pregnancy to term or opting for an abortion. The father was overwhelmingly considered to be the one to take the final decision regarding the pregnancy outcome. Irrespective of the fact that the respondents were very religious, opting for an abortion was considered acceptable under special circumstances, especially if the pregnant adolescent was doing well in school.

Conclusion

Inadequate and inappropriate communication practices around sexuality issues, as well as weak financial autonomy are the major predictors of early adolescent pregnancy in this community. The father is perceived to be the main decision maker regarding a young adolescent’s pregnancy outcome. Policy-makers should carefully evaluate the implications of this overwhelming perceived desire for the father to be the final decision-maker regarding adolescent pregnancy outcomes in this community.
Carbon nanomaterial-derived lung burden analysis using UV-Vis spectrophotometry and proteinase K digestion
Authors: Lee Dong-Keun , Jeon Soyeon , Jeong Jiyoung , Song Kyung Seuk , Cho Wan-Seob
Published: September 2020

Background

The quantification of nanomaterials accumulated in various organs is crucial in studying their toxicity and toxicokinetics. However, some types of nanomaterials, including carbon nanomaterials (CNMs), are difficult to quantify in a biological matrix. Therefore, developing improved methodologies for quantification of CNMs in vital organs is instrumental in their continued modification and application.

Results

In this study, carbon black, nanodiamond, multi-walled carbon nanotube, carbon nanofiber, and graphene nanoplatelet were assembled and used as a panel of CNMs. All CNMs showed significant absorbance at 750 nm, while their bio-components showed minimal absorbance at this wavelength. Quantification of CNMs using their absorbance at 750 nm was shown to have more than 94% accuracy in all of the studied materials. Incubating proteinase K (PK) for 2 days with a mixture of lung tissue homogenates and CNMs showed an average recovery rate over 90%. The utility of this method was confirmed in a murine pharyngeal aspiration model using CNMs at 30 μg/mouse.

Conclusions

We developed an improved lung burden assay for CNMs with an accuracy > 94% and a recovery rate > 90% using PK digestion and UV-Vis spectrophotometry. This method can be applied to any nanomaterial with sufficient absorbance in the near-infrared band and can differentiate nanomaterials from elements in the body, as well as the soluble fraction of the nanomaterial. Furthermore, a combination of PK digestion and other instrumental analysis specific to the nanomaterial can be applied to organ burden analysis.