bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of India’s national publicly funded health insurance scheme, Pradhan Mantri Jan Arogaya Yojana (PMJAY), in improving access and financial protection for hospital care: findings from household surveys in Chhattisgarh state
Authors: Garg Samir , Bebarta Kirtti Kumar , Tripathi Narayan
Published: June 2020

Background

A national Publicly Funded Health Insurance (PFHI) scheme called Pradhan Mantri Jan Arogaya Yojana (PMJAY) was launched by government of India in 2018. PMJAY seeks to cover 500 million persons with an annual cover of around 7000 USD per household. PMJAY claims to be the largest government funded health scheme globally and has attracted an international debate as a policy for Universal Health Coverage. India’s decade-long experience of the earlier national and state-specific PFHI schemes had shown poor effectiveness in financial protection. Most states in India have completed a year of implementation of PMJAY but no evaluations are available of this important scheme.

Methods

The study was designed to find out the effect of enrolment under PMJAY in improving utilisation of hospital services and financial protection in Chhattisgarh which has been a leading state in implementing PFHI in terms of enrolment and claims. The study analyses three repeated cross-sections. Two of the cross-sections are from National Sample Survey (NSS) health rounds – year 2004 when there was no PFHI and 2014 when the older PFHI scheme was in operation. Primary data was collected in 2019-end to cover the first year of PMJAY implementation and it formed the third cross-section. Multivariate analysis was carried out. In addition, Propensity Score Matching and Instrumental Variable method were applied to address the selection problem in insurance.

Results

Enrollment under PMJAY or other PFHI schemes did not increase utilisation of hospital-care in Chhattisgarh. Out of Pocket Expenditure (OOPE) and incidence of Catastrophic Health Expenditure did not decrease with enrollment under PMJAY or other PFHI schemes. The size of OOPE was significantly greater for utilisation in private sector, irrespective of enrollment under PMJAY.

Conclusion

PMJAY provided substantially larger vertical cover than earlier PFHI schemes in India but it has not been able to improve access or financial protection so far in the state. Though PMJAY is a relatively new scheme, the persistent failure of PFHI schemes over a decade raises doubts about suitability of publicly funded purchasing from private providers in the Indian context. Further research is recommended on such policies in LMIC contexts.
Changing clinical characteristics of non-cystic fibrosis bronchiectasis in children
Authors: Eralp Ela Erdem , Gokdemir Yasemin , Atag Emine , Ikizoglu Nilay Bas , Ergenekon Pinar , Yegit Cansu Yilmaz , Kut Arif , Ersu Refika , Karakoc Fazilet , Karadag Bulent
Published: June 2020

Background

The prevalence of non-cystic fibrosis (CF) bronchiectasis is increasing in both developed and developing countries in recent years. Although the main features remain similar, etiologies seem to change. Our aim was to evaluate the clinical and laboratory characteristics of our recent non-CF bronchiectasis patients and to compare these with our historical cohort in 2001.

Methods

One hundred four children with non-CF bronchiectasis followed between 2002 and 2019 were enrolled. Age of diagnosis, underlying etiology and microorganisms in sputum culture were recorded. Clinical outcomes were evaluated in terms of lung function tests and annual pulmonary exacerbation rates at presentation and within the last 12 months.

Results

Mean FEV1 and FVC %predicted at presentation improved compared to historical cohort (76.6 ± 17.1 vs. 63.3 ± 22.1 and 76.6 ± 15.1 vs. 67.3 ± 23.1, respectively; p <  0.001). There was a significant decrease in pulmonary exacerbation rate from 6.05 ± 2.88 at presentation to 3.23 ± 2.08 during follow-up (p <  0.0001). In 80.8% of patients, an underlying etiology was identified. There was an increase in primary ciliary dyskinesia (PCD) (32.7% vs. 6.3%; p = 0.001), decrease in idiopathic cases (19.2% vs. 37.8%; p = 0.03) with no change in postinfectious and immunodeficiencies as underlying etiology. Sputum cultures were positive in 77.9% of patients which was 46.9% in the historical cohort (p = 0.001).

Conclusion

Baseline pulmonary function tests were better and distribution of underlying etiology had changed with a remarkable increase in diagnosis of PCD in the recent cohort.
Hepatitis in children with tuberculosis: a case report and review of the literature
Authors: Sanchez-Codez Maria , Hunt W. Garret , Watson Joshua , Mejias Asuncion
Published: June 2020

Background

Hepatitis in young children with tuberculosis (TB) outside miliary TB is not well described and represents a challenge because of the hepatotoxicity associated with first-line anti-TB treatment.

Case presentation

We report an antibiotic naïve 13-month-old male from Nepal with pulmonary TB and hepatitis, who improved after TB treatment. We also performed a literature review for TB-associated hepatitis in children.

Conclusions

Liver function tests should be considered, when feasible, in infants and young children with pulmonary TB. Testing could help to identify and manage patients with TB-associated hepatic abnormalities, and also to establish a baseline for detection and management of liver injury associated with anti-TB therapy.
The effect of treatment with a non-invasive foot worn biomechanical device on subjective and objective measures in patients with knee osteoarthritis- a retrospective analysis on a UK population
Authors: Miles Christopher , Greene Andrew
Published: June 2020

Background

Osteoarthritis is a major cause of pain and disability worldwide, therefore ways of treating this condition are paramount to a successful health system. The purpose of the study was to investigate the changes in spatial-temporal gait parameters and clinical measurements following treatment with a non-invasive foot-worn biomechanical device on patients with knee osteoarthritis within the UK.

Methods

A retrospective analysis was carried out on 455 patients with knee osteoarthritis. All patients were evaluated using a computerized gait test and two self-assessment questionnaires (WOMAC and SF-36) at baseline and after 3 and 6 months of treatment. The biomechanical device is a shoe-like device with convex pods under the sole that have the capability of changing foot centre of pressure and training neuromuscular control. The device was individually calibrated for each patient to minimise symptoms whilst walking and train neuromuscular control. Patients used the device for short periods during activities of daily living. Repeated measures statistical analyses were performed to compare differences over time.

Results

After 6 months of treatment significant improvements were seen in all gait parameters (p < 0.01). Specifically, gait velocity, step length and single limb support of the more symptomatic knee improved by 13, 7.8 and 3%, respectively. These were supported by significant improvements in pain, function and quality of life (48.6, 45.7 and 22% respectively;p < 0.001). A sub-group analysis revealed no baseline differences between those who were recommended joint replacement and those who were not. Both groups improved significantly over time (p < 0.05 for all).

Conclusions

Our results suggest that the personalised biomechanical treatment can improve gait patterns, pain, function and quality of life. It may provide an additional solution to managing UK patients suffering from knee osteoarthritis but needs to be tested in a controlled setting first.
Comparison of antimicrobial prescribing for dental and oral infections in England and Scotland with Norway and Sweden and their relative contribution to national consumption 2010–2016
Authors: Smith Andrew , Al-Mahdi Rania , Malcolm William , Palmer Nikolaus , Dahlen Gunnar , Al-Haroni Mohammed
Published: June 2020

Background

Prescribing in dental practice has a relatively small but important contribution to the quantity of antibiotics prescribed in primary care. This study aimed to analyse antibiotic prescribing in dentistry over time (2010–2016) in 4 different Northern European countries and their relative contribution to national outpatients consumption.

Methods

This retrospective study evaluated the frequency and number of national antibiotic prescriptions written by dentists in England, Scotland, Norway and Sweden. The consumption of such antibiotics was measured using WHO defined daily doses (DDDs), DDDs per 100,000 inhabitants per day (DIDs100,000).

Results

A total of more than 27 million prescriptions (27,026,599) archived between 2010 and 2016 from the four countries were analysed. The national contribution of Norwegian dentists to the total primary care prescription during this period was 8%. The corresponding figures for Sweden, Scotland and England were 7, 6, and 8%. Dental contribution to National antibiotic use in all four countries has decreased over the study time period for commonly prescribed antibiotics in dentistry, i.e., the beta-lactams (Phenoxymethyl penicillin/Amoxicillin) and metronidazole. There were less numbers of prescriptions by dentists in Norway and Sweden compared to England and Scotland. Marked differences in some classes of antibiotics were noted with Phenoxymethyl penicillin dominating in Sweden/Norway compared to Amoxicillin and Metronidazole in England/Scotland. In England and Scotland, dentists were the largest prescribers of metronidazole in primary care. Clindamycin prescriptions was higher in Norway and Sweden.

Conclusion

Noticeable differences exist in prescribing patterns for the management of oral infections. High levels of metronidazole use in England and Scotland also require further analysis. All countries over the study period showed a decrease in total numbers of antibiotics prescribed.
Relationship between caffeine intake and infertility: a systematic review of controlled clinical studies
Authors: Bu Fan-Long , Feng Xue , Yang Xiao-Ying , Ren Jun , Cao Hui-Juan
Published: June 2020

Background

For a long time, the relationship between caffeine consumption and infertility in the general population is unclear, this study is aimed to systematically review the evidence from any type of controlled clinical studies to explore whether caffeine intake is a risk factor for human infertility.

Methods

Seven databases were searched from inception to May 2019. We included women/men without a history of infertility but were willing to have children in prospective studies and women/men who were diagnosed with infertility in retrospective studies. The observed exposure factor should be caffeine or caffeine containing beverage. Diagnosis of infertility or not for participants was the key outcome. The Newcastle-Ottawa scale (NOS) or Cochrane risk of bias tool were used to assess the methodological quality of included studies. Meta-analysis was conducted if there were acceptable clinical and statistical heterogeneity among studies. The GRADE method was used to assess the certainty of the evidence.

Results

Four studies (one cohort study and three case-control studies) involving 12,912 participants were included. According NOS, the average score of case-control studies was 6, and the cohort study achieved 9. Meta-analysis and subgroup analysis were conducted. The results showed that low (OR 0.95, 95%CI 0.78–1.16), medium (OR 1.14, 95%CI 0.69–1.86) and high doses (OR 1.86, 95%CI 0.28–12.22) of caffeine intake may not increase the risk of infertility. The quality of the current evidence bodies were all low.

Conclusion

Our study provides low quality evidence that regardless of low, medium and high doses of caffeine intake do not appear increase the risk of infertility. But the conclusion should be treated with caution.
Public preferences regarding data linkage for research: a discrete choice experiment comparing Scotland and Sweden
Authors: Tully Mary P. , Bernsten Cecilia , Aitken Mhairi , Vass Caroline
Published: June 2020

Background

There are increasing examples of linking data on healthcare resource use and patient outcomes from different sectors of health and social care systems. Linked data are generally anonymised, meaning in most jurisdictions there are no legal restrictions to their use in research conducted by public or private organisations. Secondary use of anonymised linked data is contentious in some jurisdictions but other jurisdictions are known for their use of linked data. The publics’ perceptions of the acceptability of using linked data is likely to depend on a number of factors. This study aimed to quantify the preferences of the public to understand the factors that affected views about types of linked data and its use in two jurisdictions.

Method

An online discrete choice experiment (DCE) previously conducted in Scotland was adapted and replicated in Sweden. The DCE was designed, comprising five attributes, to elicit the preferences from a representative sample of the public in both jurisdictions. The five attributes (number of levels) were: type of researcher using linked data (four); type of data being linked (four); purpose of the research (three); use of profit from using linked data (four); who oversees the research (four). Each DCE contained 6 choice-sets asking respondents to select their preferred option from two scenarios or state neither were acceptable. Background questions included socio-demographics. DCE data were analysed using conditional and heteroskedastic conditional logit models to create forecasts of acceptability.

Results

The study sample comprised members of the public living in Scotland (n = 1004) and Sweden (n = 974). All five attributes were important in driving respondents’ choices. Swedish and Scottish preferences were mostly homogenous with the exception of ‘who oversees the research using linked data’, which had relatively less impact on the choices observed from Scotland. For a defined ‘typical’ linked data scenario, the probability (on average) of acceptance was 85.7% in Sweden and 82.4% in Scotland.

Conclusion

This study suggests that the public living in Scotland and Sweden are open to using anonymised linked data in certain scenarios for research purposes but some caution is advisable if the anonymised linked data joins health to non-health data.
A national survey of private-sector outpatient care of sick infants and young children in Nepal
Authors: Ban Bharat , Hodgins Stephen , Thapa Pranita , Thapa Surakschha , Joshi Deepak , Dhungana Adhish , KC Anjana , Guenther Tanya , Adhikari Shilu , Scudder Elaine , Ram Pavani K.
Published: June 2020

Background

Previous research has documented that across South Asia, as well as in some countries in Sub-Saharan Africa, the private sector is the primary source of outpatient care for sick infants and children and, in many settings, informal providers play a bigger role than credentialed health professionals (particularly for the poorer segments of the population). This is the case in Nepal. This study sought to characterize medicine shop-based service providers in rural areas and small urban centers in Nepal, their role in the care and treatment of sick infants and children (with a particular focus on infants aged < 2 months), and the quality of the care provided. A secondary objective was to characterize availability and quality of such care provided by physicians in these settings.

Methods

A nationally representative sample of medicine shops was drawn, in rural settings and small urban centers in Nepal, from 25 of the 75 districts in Nepal, using multi-stage cluster methodology, with a final sample of 501 shops and 82 physician-run clinics. Face-to-face interviews were conducted.

Results

Most medicine shops outside urban areas were not registered with the Department of Drug Administration (DDA). Most functioned as de facto clinics, with credentialed paramedical workers (having 2–3 years of training) diagnosing patients and making treatment decisions. Such a role falls outside their formally sanctioned scope of practice. Quality of care problems were identified among medicine shop-based providers and physicians, including over-use of antibiotics for treating diarrhea, inaccurate weighing technique to determine antibiotic dose, and inappropriate use of injectable steroids for treating potentially severe infections in young infants.

Conclusions

Medicine shop-based practitioners in Nepal represent a particular type of informal provider; although most have recognized paramedical credentials, they offer services falling outside their formal scope of practice. Nevertheless, given the large proportion of the population served by these practitioners, engagement to strengthen quality of care by these providers and referral to the formal health sector is warranted.
Multi-omics analysis delineates the distinct functions of sub-cellular acetyl-CoA pools in Toxoplasma gondii
Authors: Kloehn Joachim , Oppenheim Rebecca D. , Siddiqui Ghizal , De Bock Pieter-Jan , Kumar Dogga Sunil , Coute Yohann , Hakimi Mohamed-Ali , Creek Darren J. , Soldati-Favre Dominique
Published: June 2020

Background

Acetyl-CoA is a key molecule in all organisms, implicated in several metabolic pathways as well as in transcriptional regulation and post-translational modification. The human pathogenToxoplasma gondiipossesses at least four enzymes which generate acetyl-CoA in the nucleo-cytosol (acetyl-CoA synthetase (ACS); ATP citrate lyase (ACL)), mitochondrion (branched-chain α-keto acid dehydrogenase-complex (BCKDH)) and apicoplast (pyruvate dehydrogenase complex (PDH)). Given the diverse functions of acetyl-CoA, we know very little about the role of sub-cellular acetyl-CoA pools in parasite physiology.

Results

To assess the importance and functions of sub-cellular acetyl-CoA-pools, we measured the acetylome, transcriptome, proteome and metabolome of parasites lacking ACL/ACS or BCKDH. We demonstrate that ACL/ACS constitute a synthetic lethal pair. Loss of both enzymes causes a halt in fatty acid elongation, hypo-acetylation of nucleo-cytosolic and secretory proteins and broad changes in gene expression. In contrast, loss of BCKDH results in an altered TCA cycle, hypo-acetylation of mitochondrial proteins and few specific changes in gene expression. We provide evidence that changes in the acetylome, transcriptome and proteome of cells lacking BCKDH enable the metabolic adaptations and thus the survival of these parasites.

Conclusions

Using multi-omics and molecular tools, we obtain a global and integrative picture of the role of distinct acetyl-CoA pools inT. gondiiphysiology. Cytosolic acetyl-CoA is essential and is required for the synthesis of parasite-specific fatty acids. In contrast, loss of mitochondrial acetyl-CoA can be compensated for through metabolic adaptations implemented at the transcriptional, translational and post-translational level.
FBXO2 modulates STAT3 signaling to regulate proliferation and tumorigenicity of osteosarcoma cells
Authors: Zhao Xunming , Guo Weichun , Zou Lixue , Hu Biao
Published: June 2020

Background

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, and hyperproliferation of cells is a major problem of OS. FBXO2 belongs to the family of F-box proteins, and is a substrate recognition component of the Skp1-Cul1-F-box protein (SCF) E3 ubiquitin ligase complex with specificity for high-mannose glycoproteins. The aim of the present study was to investigate the critical role of FBXO2 in OS cells.

Methods

The protein and mRNA expression levels of FBXO2 in clinic OS patients were measured by quantitative real time-polymerase chain reaction (qRT-PCR), Western blot and Immunohistochemical (IHC) staining assays, respectively. The FBXO2 overexpression model was constructed by retro-virus transfection in OS cells. FBXO2 knockout (KO) cells were generated by Clustered regularly interspaced short palindromic repeat (CRISPR)–CRISPR-associated protein 9 (Cas9) assay. Cell counting and colony formation assays were used to analyze the effect of FBXO2 on the biological function of OS cells. FBXO2 KO cells were injected into nude mice to observe tumor growth in vivo. The interaction between FBXO2 and IL-6 was detected by immunoprecipitation. Luciferase assay was used to determine the transcriptional activity of STAT3.

Results

Here, we show that FBXO2 is significantly up-regulated in clinical OS samples compared to adjacent normal tissues. Ectopic expression of FBXO2 leads to increased OS cell proliferation and colony-forming ability, while FBXO2 knockout by CRISPR-Cas9-based gene editing has the opposite effect. In addition, the glycoprotein recognition activity of FBXO2 is required for its biological function in OS. In vivo experiments showed that FBXO2 knockout greatly impaired the tumorigenicity of OS cells in nude mice. At the molecular level, we found that knocking out FBXO2 can significantly inhibit STAT3 phosphorylation and downstream target gene expression through IL-6R stabilization.

Conclusion

Together, these results indicate that FBXO2 promotes OS development by activating the STAT3 signaling pathway, suggesting that FBXO2 may be a new target for OS treatment.
Assessment of attitudes toward functional foods based on theory of planned behavior: validation of a questionnaire
Authors: Salmani Fatemeh , Norozi Ensiyeh , Moodi Mitra , Zeinali Tayebeh
Published: June 2020

Background

The objectives of this study are to construct a cultural adopted questionnaire for evaluation of consumer’s attitudes toward functional foods among Iranian’s population according to Theory of Planned Behavior (TPB) and to investigate the attitudes toward vitamin enriched foods (VEF).

Methods

Participants were students of Birjand University of Medical Sciences (BUMS). Exploratory factor analysis (EFA), Confirmatory Factor Analysis (CFA) and reliability assessment were performed. The construct validity of questionnaire determined by EFA and confirmed by CFA.

Results

The overall Cronbach’s alpha of questionnaire was 0.78. The three domains of TPB model were significantly associated with the total score of attitude toward functional foods questionnaire (AFFQ). Attitudes and subjective norms could successfully predict the consumption of VEF (p < 0.023 and p < 0.001, respectively), but perceived control construct could not perform the prediction (p < 0.219).

Conclusion

AFFQ is a valid and reliable instrument to measure the attitudes of consumers toward consumption of functional foods in Iran.
Associations of linoleic acid with markers of glucose metabolism and liver function in South African adults
Authors: Pertiwi Kamalita , Küpers Leanne K. , Geleijnse Johanna M. , Zock Peter L. , Wanders Anne J. , Kruger Herculina S. , van Zyl Tertia , Kruger Iolanthé M. , Smuts Cornelius M.
Published: June 2020

Background

The relation between dietary and circulating linoleic acid (18:2 n-6, LA), glucose metabolism and liver function is not yet clear. Associations of dietary and circulating LA with glucose metabolism and liver function markers were investigated.

Methods

Cross-sectional analyses in 633 black South Africans (aged > 30 years, 62% female, 51% urban) without type 2 diabetes at baseline of the Prospective Urban Rural Epidemiology study. A cultural-sensitive 145-item food-frequency questionnaire was used to collect dietary data, including LA (percentage of energy; en%). Blood samples were collected to measure circulating LA (% total fatty acids (FA); plasma phospholipids), plasma glucose, glycosylated hemoglobin (HbA1c), serum gamma-glutamyl transferase (GGT), alanine (ALT) and aspartate aminotransferase (AST). Associations per 1 standard deviation (SD) and in tertiles were analyzed using multivariable regression.

Results

Mean (±SD) dietary and circulating LA was 6.8 (±3.1) en% and 16.0 (±3.5) % total FA, respectively. Dietary and circulating LA were not associated with plasma glucose or HbA1c (β per 1 SD: − 0.005 to 0.010, P > 0.20). Higher dietary LA was generally associated with lower serum liver enzymes levels. One SD higher circulating LA was associated with 22% lower serum GGT (β (95% confidence interval): − 0.25 (− 0.31, − 0.18), P < 0.001), but only ≤9% lower for ALT and AST. Circulating LA and serum GGT associations differed by alcohol use and locality.

Conclusion

Dietary and circulating LA were inversely associated with markers of impaired liver function, but not with glucose metabolism. Alcohol use may play a role in the association between LA and liver function.

Trial registration

PURE North-West Province South Africa study described in this manuscript is part of the PURE study. The PURE study is registered in ClinicalTrials.gov (Identifier: NCT03225586; URL).
Association between apolipoprotein E gene polymorphism and the risk of coronary artery disease in Hakka postmenopausal women in southern China
Authors: Hou Jingyuan , Deng Qiaoting , Guo Xuemin , Deng Xunwei , Zhong Wei , Zhong Zhixiong
Published: June 2020

Background

Apolipoprotein E (APOE) is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The aim of the present study was to investigate the possible association between APOE gene polymorphism and the risk of CAD in postmenopausal Hakka women in southern China.

Methods

The APOE genotypes of 653 CAD patients and 646 control participants were determined by the polymerase chain reaction (PCR) and hybridization to a Sinochip.

Results

The prevalence of each APOE genotype differed between CAD patients and control participants (P = 0.011). The E3/E3 genotype was the most common and the E2/E2 genotype was the least common in the study sample. Moreover, the presence of ε4 allele was associated with higher serum concentrations of triglycerides (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C), and lower concentration of high-density lipoprotein-cholesterol (HDL-C). Multiple logistic regression analysis revealed that participants with ε4 allele have a significantly higher risk of CAD after adjustment for the presence of diabetes mellitus and hypertension, and their serum uric acid, TC, and LDL-C concentrations (adjusted odds ratio (OR) 1.50, 95% confidence interval (CI) 1.10–2.05, P = 0.010).

Conclusions

The present results suggest that APOE polymorphism is associated with a higher risk of CAD in postmenopausal Hakka women in southern China.
Combining texture features of whole slide images improves prognostic prediction of recurrence-free survival for cutaneous melanoma patients
Authors: Peng Yanbin , Chu Yunfeng , Chen Zhong , Zhou Wen , Wan Shengxiang , Xiao Yingfeng , Zhang Youlong , Li Jialu
Published: June 2020

Background

Accurate prediction of recurrence-free survival (RFS) is important for the prognosis of cutaneous melanoma patients. The image-based pathological examination remains as the gold standard for diagnosis. It is of clinical interest to account for computer-aided processing of pathology image when performing prognostic analysis.

Methods

We enrolled in this study a total of 152 patients from TCGA-SKCM (The Cancer Genome Atlas Skin Cutaneous Melanoma project) with complete information in recurrence-related survival time, baseline variables (clinicopathologic variables, mutation status of BRAF and NRAS genes), gene expression data, and whole slide image (WSI) features. We preprocessed WSI to segment global or nucleus areas, and extracted 3 types of texture features from each region. We performed cross validation and used multiple evaluation metrics including C-index and time-dependent AUC to determine the best model of predicting recurrence events. We further performed differential gene expression analysis between the higher and lower-risk groups within AJCC pathologic tumor stage III patients to explore the underlying molecular mechanisms driving risk stratification.

Results

The model combining baseline variables and WSI features had the best performance among models with any other types of data integration. The prognostic risk score generated by this model could provide a higher-resolution risk stratification within pathologically defined subgroups. We found the selected image features captured important immune-related variations, such as the aberration of expression in T cell activation and proliferation gene sets, and therefore contributed to the improved prediction.

Conclusions

Our study provided a prognostic model based on the combination of baseline variables and computer-processed WSI features. This model provided more accurate prediction than models based on other types of data combination in recurrence-free survival analysis.

Trial registration

This study was based on public open data from TCGA and hence the study objects were retrospectively registered.
The TNF/TNFR2 signaling pathway is a key regulatory factor in endothelial progenitor cell immunosuppressive effect
Authors: Naserian Sina , Abdelgawad Mohamed Essameldin , Afshar Bakshloo Mazdak , Ha Guillaume , Arouche Nassim , Cohen José L. , Salomon Benoît L. , Uzan Georges
Published: June 2020

Background

Endothelial progenitor cells (EPCs) are non-differentiated endothelial cells (ECs) present in blood circulation that are involved in neo-vascularization and correction of damaged endothelial sites. Since EPCs from patients with vascular disorders are impaired and inefficient, allogenic sources from adult or cord blood are considered as good alternatives. However, due to the reaction of immune system against allogenic cells which usually lead to their elimination, we focused on the exact role of EPCs on immune cells, particularly, T cells which are the most important cells applied in immune rejection. TNFα is one of the main activators of EPCs that recognizes two distinct receptors. TNFR1 is expressed ubiquitously and its interaction with TNFα leads to differentiation and apoptosis, whereas, TNFR2 is expressed predominantly on ECs, immune cells and neural cells and is involved in cell survival and proliferation. Interestingly, it has been shown that different immunosuppressive cells express TNFR2 and this is directly related to their immunosuppressive efficiency. However, little is known about immunological profile and function of TNFR2 in EPCs.

Methods

Using different in-vitro combinations, we performed co-cultures of ECs and T cells to investigate the immunological effect of EPCs on T cells. We interrupted in the TNFα/TNFR2 axis either by blocking the receptor using TNFR2 antagonist or blocking the ligand using T cells derived from TNFα KO mice.

Results

We demonstrated that EPCs are able to suppress T cell proliferation and modulate them towards less pro-inflammatory and active phenotypes. Moreover, we showed that TNFα/TNFR2 immune-checkpoint pathway is critical in EPC immunomodulatory effect.

Conclusions

Our results reveal for the first time a mechanism that EPCs use to suppress immune cells, therefore, enabling them to form new immunosuppressive vessels. Furthermore, we have shown the importance of TNFα/TNFR2 axis in EPCs as an immune checkpoint pathway. We believe that targeting TNFR2 is especially crucial in cancer immune therapy since it controls two crucial aspects of tumor microenvironment: 1) Immunosuppression and 2) Angiogenesis.
Estrogen receptor α as a predictive biomarker for survival in human papillomavirus-positive oropharyngeal squamous cell carcinoma
Authors: Kwon Soohyeon , Ahn Soon-Hyun , Jeong Woo-Jin , Jung Young Ho , Bae Yun Jung , Paik Jin Ho , Chung Jin-Haeng , Kim Hyojin
Published: June 2020

Background

Although oropharyngeal squamous cell carcinoma (OPSCC) with human papillomavirus (HPV) infection has a good prognosis, the accurate prediction of survival and risk of treatment failure is essential to design deintensification regimens. Here, we investigated estrogen receptor α (ERα) as a prognostic biomarker with therapeutic implications in OPSCC alongside factors associated with HPV infection.

Methods

We performed immunohistochemistry for ERα and p53 using formalin-fixed, paraffin-embedded tissues and assessed the HPV status using p16 immunohistochemistry and HPV DNA testing in 113 consecutive patients with OPSCC treated with surgical resection or radiotherapy/chemoradiotherapy.

Results

ERα expression and p53 alteration was observed in 35.4% and 21.2% OPSCCs; 45.6% and 1.3% p16+/HPV+ OPSCCs; and 11.5% and 76.9% p16− OPSCCs, respectively. These data suggest that OPSCC pathogenesis varies with HPV status. Furthermore, ERα expression was associated with improved overall survival (OS) in both HPV+ (p16+/HPV+ OPSCC) and p16+ (p16+ OPSCC irrespective of HPV status) models (p = 0.005 and p = 0.006, respectively) and with improved OS adjusted for stage (p = 0.037, hazard ratio: 0.109, 95% confidence interval 0.013–0.871) in the p16+ model.

Conclusions

ERα is a potential predictive biomarker for improved survival in both HPV+ and p16+ OPSCC models.
Perceptions and experiences of men and women towards acceptability and use of contraceptives in underserved areas of Karachi, Pakistan: a midline qualitative assessment of Sukh initiative, Karachi Pakistan
Authors: Saleem Sarah , Rizvi Narjis , Shahil Feroz Anam , Reza Sayyeda , Jessani Saleem , Abrejo Farina
Published: June 2020

Background

Family planning (FP) is an essential component of Sustainable Development Goals (SDG) and contributes directly to SDG targets 3.7 and 5.6. In Pakistan, contraceptive use has remained stagnant over the past 5 years. This change has been very slow when compared to the FP2020 pledge. The Sukh initiative project was conceived and implemented to alleviate these challenges by providing access to quality contraceptive methods in some underserved areas of Karachi, Pakistan. A qualitative study was conducted to understand the perceptions and experiences of men and women towards acceptability and contraceptive use.

Methods

A qualitative study was conducted at ten Sukh stations located in four towns of Karachi. Focus group discussions (FGDs) were conducted with married women of reproductive age (MWRA) and married men who received FP services through the Sukh initiative. Study participants were purposively sampled for focus group discussions (FGDs). Interview data was manually transcribed and analyzed using thematic analysis.

Results

A total of 20 FDGs (Men = 10 FGDs; MWRA = 10 FGDs) were conducted. Three overarching themes were identified: (I) Appropriateness and means to promote contraceptive use; (II) Equity and Accessibility to contraceptives; and (III) Perspective on available FP services. Generally, both men and women were informed about FP methods but women were more cognizant of FP information. The door to door services by community health workers in Sukh initiative areas was largely appreciated both by women and men as it has made the accessibility and availability of the information and services easy. Women suggested that the Sukh initiative should bring some strategies that can help men broaden their perspective towards FP. The study informed that the men feel left out from the FP programs. Therefore, male participants expressed keen interest in initiatives for men in their communities that would cater to their FP needs.

Conclusions

This qualitative study provided a unique opportunity to understand the perceptions of men and women towards the phenomena of contraceptive use. The study identified the need for trained and qualified female and male healthcare providers and well-established health facilities alongside door-to-door services.
Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression
Authors: Aleksandrova Lily R. , Wang Yu Tian , Phillips Anthony G.
Published: June 2020

Accumulating evidence implicates dysregulation of hippocampal synaptic plasticity in the pathophysiology of depression. However, the effects of ketamine on synaptic plasticity and their contribution to its mechanism of action as an antidepressant, are still unclear. We investigated ketamine’s effects on in vivo dorsal hippocampal (dHPC) synaptic plasticity and their role in mediating aspects of antidepressant activity in the Wistar-Kyoto (WKY) model of depression. dHPC long-term potentiation (LTP) was significantly impaired in WKY rats compared to Wistar controls. Importantly, a single low dose (5 mg/kg, ip) of ketamine or its metabolite, (2R,6R)-HNK, rescued the LTP deficit in WKY rats at 3.5 h but not 30 min following injection, with residual effects at 24 h, indicating a delayed, sustained facilitatory effect on dHPC synaptic plasticity. Consistent with the observed dHPC LTP deficit, WKY rats exhibited impaired hippocampal-dependent long-term spatial memory as measured by the novel object location recognition test (NOLRT), which was effectively restored by pre-treatment with both ketamine or (2R,6R)-HNK. In contrast, in WKYs, which display abnormal stress coping, ketamine, but not (2R,6R)-HNK, had rapid and sustained effects in the forced swim test (FST), a commonly used preclinical screen for antidepressant-like activity. The differential effects of (2R,6R)-HNK observed here reveal a dissociation between drug effects on FST immobility and dHPC synaptic plasticity. Therefore, in the WKY rat model, restoring dHPC LTP was not correlated with ketamine’s effects in FST, but importantly, may have contributed to the reversal of hippocampal-dependent cognitive deficits, which are critical features of clinical depression. Our findings support the theory that ketamine may reverse the stress-induced loss of connectivity in key neural circuits by engaging synaptic plasticity processes to “reset the system”.
Intraventricular IL-17A administration activates microglia and alters their localization in the mouse embryo cerebral cortex
Authors: Sasaki Tetsuya , Tome Saki , Takei Yosuke
Published: June 2020

Viral infection during pregnancy has been suggested to increase the probability of autism spectrum disorder (ASD) in offspring via the phenomenon of maternal immune activation (MIA). This has been modeled in rodents. Maternal T helper 17 cells and the effector cytokine, interleukin 17A (IL-17A), play a central role in MIA-induced behavioral abnormalities and cortical dysgenesis, termed cortical patch. However, it is unclear how IL-17A acts on fetal brain cells to cause ASD pathologies. To assess the effect of IL-17A on cortical development, we directly administered IL-17A into the lateral ventricles of the fetal mouse brain. We analyzed injected brains focusing on microglia, which express IL-17A receptors. We found that IL-17A activated microglia and altered their localization in the cerebral cortex. Our data indicate that IL-17A activates cortical microglia, which leads to a cascade of ASD-related brain pathologies, including excessive phagocytosis of neural progenitor cells in the ventricular zone.
Clinical and bacteriological profile of diabetic foot infections in a tertiary care
Authors: Goh Teik Chiang , Bajuri Mohd Yazid , C. Nadarajah Sivapathasundaram , Abdul Rashid Abdul Halim , Baharuddin Suhaila , Zamri Kamarul Syariza
Published: June 2020

Background

Diabetic foot infection is a worldwide health problem is commonly encountered in daily practice. This study was conducted to identify the microbiological profile and antibiotic sensitivity patterns of causative agents identified from diabetic foot infections (DFIs). In addition, the assessment included probable risk factors contributing to infection of ulcers that harbour multidrug‐resistant organisms (MDROs) and their outcomes.

Methods

We carried out a prospective analysis based on the DFI samples collected from 2016 till 2018. Specimens were cultured with optimal techniques in addition to antibiotic susceptibility based on recommendations from The Clinical and Laboratory Standards Institute (CLSI). A total of 1040 pathogens were isolated with an average of 1.9 pathogens per lesion in 550 patients who were identified with having DFIs during this interval.

Results

A higher percentage of Gram‐negative pathogens (54%) were identified as compared with Gram‐positive pathogens (33%) or anaerobes (12%). A total of 85% of the patients were found to have polymicrobial infections.Pseudomonas aeruginosa(19%),Staphylococcus aureus(11%) and Bacteroides species (8%) appeared to be the predominant organisms isolated. In the management of Gram‐positive bacteria, the most efficacious treatment was seen with the use of Vancomycin, while Imipenem and Amikacin proved to be effective in the treatment of Gram‐negative bacteria.

Conclusion

DFI's are common among Malaysians with diabetes, with a majority of cases displaying polymicrobial aetiology with multi‐drug resistant isolates. The data obtained from this study will be valuable in aiding future empirical treatment guidelines in the treatment of DFIs. This study investigated the microbiology of DFIs and their resistance to antibiotics in patients with DFIs that were managed at a Tertiary Care Centre in Malaysia.
Health-related quality of life of children and their parents 2 years after critical illness: pre-planned follow-up of the PEPaNIC international, randomized, controlled trial
Authors: Hordijk José , Verbruggen Sascha , Vanhorebeek Ilse , Güiza Fabian , Wouters Pieter , Van den Berghe Greet , Joosten Koen , Dulfer Karolijn
Published: June 2020

Background

Pediatric intensive care unit (PICU) survivors are at risk for prolonged morbidities interfering with daily life. The current study examined parent-reported health-related quality of life (HRQoL) in former critically ill children and parents themselves and aimed to determine whether withholding parenteral nutrition (PN) in the first week of critical illness affected children’s and parents’ HRQoL 2 years later.

Methods

Children who participated in the pediatric early versus late parenteral nutrition in critical illness (PEPaNIC) trial and who were testable 2 years later (n = 1158) were included. Their HRQoL outcomes were compared with 405 matched healthy controls. At PICU admission, children had been randomly assigned to early-PN or late-PN. In the early-PN group, PN was initiated within 24 h after PICU admission. In the late-PN group, PN was withheld for up to 1 week in the PICU. Parents completed the Infant Toddler Quality of Life Questionnaire (ITQOL; age 2–3 years) or the Child Health Questionnaire-Parent Form 50 (CHQ-PF50; age 4–18 years). Besides, they completed the Health Utility Index (HUI) and the Short Form Health Survey (SF-12) regarding their child’s and their own HRQoL, respectively.

Results

For the total age group of 786 post-PICU survivors, parents reported lower scores for almost all HRQoL scales compared to healthy children. Age-specifically, younger critically ill children (2.5 to 3 years old) scored worse for growth and development and older children (4–18 years old) scored worse for role functioning and mental health. Parents’ own mental and physical HRQoL was comparable to that of healthy control parents. No HRQoL differences were found between children in the late-PN and those in the early-PN group.

Conclusions

Parent-reported HRQoL of children 2 years after critical illness was impaired compared with healthy controls. In relation to their child’s HRQoL, parents reported impairments in emotions, personal time, and family activities; however, their own HRQoL was not impaired. Withholding PN in the first week during critical illness had no impact on longer-term HRQoL of the child.

Trial registration

Clinical trials, NCT01536275. Registered 22 February 2012
3D genome architecture coordinates trans and cis regulation of differentially expressed ear and tassel genes in maize
Authors: Sun Yonghao , Dong Liang , Zhang Ying , Lin Da , Xu Weize , Ke Changxiong , Han Linqian , Deng Lulu , Li Guoliang , Jackson David , Li Xingwang , Yang Fang
Published: June 2020

Background

Maize ears and tassels are two separate types of inflorescence which are initiated by similar developmental processes but gradually develop distinct architectures. However, coordinated trans and cis regulation of differentially expressed genes determining ear and tassel architecture within the 3D genome context is largely unknown.

Results

We identify 56,055 and 52,633 open chromatin regions (OCRs) in developing maize ear and tassel primordia using ATAC-seq and characterize combinatorial epigenome features around these OCRs using ChIP-seq, Bisulfite-seq, and RNA-seq datasets. Our integrative analysis of coordinated epigenetic modification and transcription factor binding to OCRs highlights the cis and trans regulation of differentially expressed genes in ear and tassel controlling inflorescence architecture. We further systematically map chromatin interactions at high-resolution in corresponding tissues using in situ digestion-ligation-only Hi-C (DLO Hi-C). The extensive chromatin loops connecting OCRs and genes provide a 3D view on cis- and trans-regulatory modules responsible for ear- and tassel-specific gene expression. We find that intergenic SNPs tend to locate in distal OCRs, and our chromatin interaction maps provide a potential mechanism for trait-associated intergenic SNPs that may contribute to phenotypic variation by influencing target gene expression through chromatin loops.

Conclusions

Our comprehensive epigenome annotations and 3D genome maps serve as valuable resource and provide a deep understanding of the complex regulatory mechanisms of genes underlying developmental and morphological diversities between maize ear and tassel.
Correction to: Effectiveness of a multi-level intervention to reduce men’s perpetration of intimate partner violence: a cluster randomised controlled trial
Authors: Christofides Nicola J. , Hatcher Abigail M. , Rebombo Dumisani , McBride Ruari-Santiago , Munshi Shehnaz , Pino Angelica , Abdelatif Nada , Peacock Dean , Levin Jonathan , Jewkes Rachel K.
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Fast-track- recovery surgery with a whey-protein-infused carbohydrate-loading drink pre-operatively and early oral feeding post-operatively among surgical gynaecological cancer patients: study protocol of an open-labelled, randomised controlled trial
Authors: Ho Chiou Yi , Ibrahim Zuriati , Abu Zaid Zalina , Mat Daud Zulfitri ‘Azuan , Md Yusop Nor Baizura
Published: June 2020

Introduction

There has been growing evidence on the favourable outcomes of fast-track-recovery (FTR) surgery; to expedite recovery, minimise complications, and reduce the length of hospital stay for surgical patients. However, there is lack of evidence on the effectiveness of FTR in surgical gynaecological cancer (GC) patients. Most of the previous studies did not focus on feeding composition in the FTR surgery protocol. This study aims to determine the effectiveness of FTR feeding with a whey-protein-infused carbohydrate-loading drink pre-operatively and early oral feeding post-operatively on post-operative outcomes among surgical GC patients.

Methods/design

This open-labelled, randomised controlled trial (RCT) will randomly allocate patients into intervention and control groups. Ambulated Malaysian aged over 18 years and scheduled for elective surgery for (suspected) GC, will be included in this study. The intervention group will be given whey-protein-infused carbohydrate-loading drinks on the evening before their operation and 3 h before their operation as well as started on early oral feeding 4 h post-operatively. The control group will be fasted overnight pre-operation and only allowed plain water, and return to a normal diet is allowed when bowel sounds return post-operatively. The primary outcomes of study are length of post-operative hospital stay, length of clear-fluid tolerance, solid-food tolerance and bowel function. Additional outcome measures are changes in nutritional status, biochemical profile and functional status. Data will be analysed on an intention-to-treat basis.

Trial registration

ClinicalTrials.gov, ID: NCT03667755. Retrospectively registered on 12 September 2018;

Protocol version: version 3 dated 27 September 2017.