bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of homologous cancer cell membrane camouflage in a nano-drug delivery system for the treatment of lymphoma
Authors: Zhao Qiangqiang , Sun Xiaoying , Wu Bin , Shang Yinghui , Huang Xueyuan , Dong Hang , Liu Haiting , Chen Wansong , Gui Rong , Li Jian
Published: January 2021

Background

Non-Hodgkin’s lymphoma (NHL) possesses great heterogeneity in cytogenetics, immunophenotype and clinical features, and chemotherapy currently serves as the main treatment modality. Although employing monoclonal antibody targeted drugs has significantly improved its overall efficacy, various patients continue to suffer from drug resistance or recurrence. Chinese medicine has long been used in the treatment of malignant tumors. Therefore, we constructed a low pH value sensitivity drug delivery system based on the cancer cell membrane modified mesoporous silica nanoparticles loaded with traditional Chinese medicine, which can reduce systemic toxicity and improve the therapeutic effect for the targeted drug delivery of tumor cells.

Results

Accordingly, this study put forward the construction of a nano-platform based on mesoporous silica nanoparticles (MSNs) loaded with the traditional Chinese medicine isoimperatorin (ISOIM), which was camouflaged by the cancer cell membrane (CCM) called CCM@MSNs-ISOIM. The proposed nano-platform has characteristics of immune escape, anti-phagocytosis, high drug loading rate, low pH value sensitivity, good biocompatibility and active targeting of the tumor site, blocking the lymphoma cell cycle and promoting mitochondrial-mediated apoptosis.

Conclusions

Furthermore, this study provides a theoretical basis in finding novel clinical treatments for lymphoma.
Effect of stroma on the behavior of temoporfin-loaded lipid nanovesicles inside the stroma-rich head and neck carcinoma spheroids
Authors: Yakavets Ilya , Francois Aurelie , Lamy Laureline , Piffoux Max , Gazeau Florence , Wilhelm Claire , Zorin Vladimir , Silva Amanda K. A. , Bezdetnaya Lina
Published: January 2021

Background

Despite the highly expected clinical application of nanoparticles (NPs), the translation of NPs from lab to the clinic has been relatively slow. Co-culture 3D spheroids account for the 3D arrangement of tumor cells and stromal components, e.g., cancer-associated fibroblasts (CAFs) and extracellular matrix, recapitulating microenvironment of head and neck squamous cell carcinoma (HNSCC). In the present study, we investigated how the stroma-rich tumor microenvironment affects the uptake, penetration, and photodynamic efficiency of three lipid-based nanoformulations of approved in EU photosensitizer temoporfin (mTHPC): Foslip® (mTHPC in conventional liposomes), drug-in-cyclodextrin-in-liposomes (mTHPC-DCL) and extracellular vesicles (mTHPC-EVs).

Results

Collagen expression in co-culture stroma-rich 3D HNSCC spheroids correlates with the amount of CAFs (MeWo cells) in individual spheroid. The assessment of mTHPC loading demonstrated that Foslip®, mTHPC-DCL and mTHPC-EVs encapsulated 0.05 × 10− 15 g, 0.07 × 10− 15 g, and 1.3 × 10− 15 g of mTHPC per nanovesicle, respectively. The mid-penetration depth of mTHPC NPs in spheroids was 47.8 µm (Foslip®), 87.8 µm (mTHPC-DCL), and 49.7 µm (mTHPC-EVs), irrespective of the percentage of stromal components. The cellular uptake of Foslip® and mTHPC-DCL was significantly higher in stroma-rich co-culture spheroids and was increasing upon the addition of serum in the culture medium. Importantly, we observed no significant difference between PDT effect in monoculture and co-culture spheroids treated with lipid-based NPs. Overall, in all types of spheroids mTHPC-EVs demonstrated outstanding total cellular uptake and PDT efficiency comparable to other NPs.

Conclusions

The stromal microenvironment strongly affects the uptake of NPs, while the penetration and PDT efficacy are less sensitive to the presence of stromal components. mTHPC-EVs outperform other lipid nanovesicles due to the extremely high loading capacity. The results of the present study enlarge our understanding of how stroma components affect the delivery of NPs into the tumors.
Synergy of hypoxia relief and heat shock protein inhibition for phototherapy enhancement
Authors: Zhang Gutian , Cheng Wenting , Du Lin , Xu Chuanjun , Li Jinlong
Published: January 2021

Background

Phototherapy is a promising strategy for cancer therapy by reactive oxygen species (ROS) of photodynamic therapy (PDT) and hyperthermia of photothermal therapy (PTT). However, the therapeutic efficacy was restricted by tumor hypoxia and thermal resistance of increased expression of heat shock protein (Hsp). In this study, we developed albumin nanoparticles to combine hypoxia relief and heat shock protein inhibition to overcome these limitations for phototherapy enhancement.

Results

Near-infrared photosensitizer (IR780) and gambogic acid (GA, Hsp90 inhibitor) were encapsulated into albumin nanoparticles via hydrophobic interaction, which was further deposited MnO2on the surface to form IGM nanoparticles. Both in vitro and in vivo studies demonstrated that IGM could catalyze overexpress of hydrogen peroxide to relive hypoxic tumor microenvironment. With near infrared irradiation, the ROS generation was significantly increase for PDT enhancement. In addition, the release of GA was promoted by irradiation to bind with Hsp90, which could reduce cell tolerance to heat for PTT enhancement. As a result, IGM could achieve better antitumor efficacy with enhanced PDT and PTT.

Conclusion

This study develops a facile approach to co-deliver IR780 and GA with self-assembled albumin nanoparticles, which could relive hypoxia and suppress Hsp for clinical application of cancer phototherapy.
Harm reduction in Europe: a framework for civil society-led monitoring
Authors: Rigoni Rafaela , Tammi Tuukka , van der Gouwe Daan , Schatz Eberhard
Published: January 2021

Background

Civil society organisations (CSOs) play a vital role in developing and implementing effective measures to reduce the harms of drug use. They are also fundamental actors to monitor and evaluate programmes and policies for improvement. While harm reduction services are subject to monitoring, and international and European indicators exist, a framework for civil society-led monitoring does not exist. This paper analyses the challenges and added values of developing such a framework for the European region.

Methods

Since 2018, a technical working group within Correlation-European Harm Reduction Network (C-EHRN) is developing and revising a monitoring framework, collecting—through National Focal Points—the experience of harm reduction service providers and service users in 34 European countries. The first round of data collection, in 2019, focused on hepatitis C, overdose prevention, new drug trends and civil society involvement in drug policies.

Results

Developing CSO-based harm reduction monitoring is a learning by doing process. Assuring reliability and national representativeness of the data was a central challenge. As most CSOs have little or no experience with monitoring and research and work in a local-based context, the monitoring approach and its indicators were adjusted to the local context in the second round, bringing more in-depth information and helping to improve results’ reliability. While this implied shifting from the initial focus on comparing responses at a national level, the change to collecting qualitative data reflecting local realities of service policies and delivery provides the foundations for a critical appraisal of these realities against European policy goals. This allowed to map discrepancies between official policies and their implementation, as well as identify gaps in and complement data collection from national-level agencies.

Conclusions

By focusing on local experiences regarding the delivery of global and European policy targets, C-EHRN monitoring uses the unique strengths of its CSOs network and generates information that complements the reporting by other monitoring agencies. Data reflecting the CSOs perspective is essential for optimising local planning of service provision and development of effective and respectful drug policies at national and European level. If data quality issues, as well as the sustainability of reporting, are adequately addressed, civil society monitoring can provide excellent added value for the monitoring of harm reduction in Europe.
Unprovoked internal jugular vein thrombosis: a case report and literature review
Authors: Payrard Loïc , Iten Léa , Donzé Jacques , John Gregor
Published: January 2021

Background

Managing thrombosis in rare sites is challenging. Existing studies and guidelines provide detailed explanations on how to overcome lower-limb thromboses and pulmonary embolisms, but few studies have examined thrombosis in rare sites. Lack of data makes clinical practice heterogeneous. Recommendations for diagnosing, treating, and following-up internal jugular vein thrombosis are not clearly defined and mostly based on adapted guidelines for lower-limb thrombosis.

Case presentation

A 52-year-old Caucasian woman came to the Emergency Department with chest, neck, and left arm pain. Computed tomography imagery showed a left internal jugular vein thrombosis. An extensive workup revealed a heterozygous factor V Leiden gene. Therapy was initiated with intravenous unfractionated heparin, then switched to oral acenocoumarol, which resolved the symptoms. Based on this case presentation and a literature review, we summarize the causes, treatment options, and prognosis of unprovoked internal jugular vein thrombosis.

Conclusions

Managing internal jugular vein thrombosis lacks scientific data from large randomized clinical trials, partly because such thromboses are rare. Our literature review suggested that clinical treatments for internal jugular vein thrombosis often followed recommendations for treating lower-limb thrombosis. Future specific studies are required to guide clinicians on the modalities of diagnosis, screening for thrombophilia or oncologic disease, treatment duration, and follow-up.
Fatal pulmonary arterial thrombosis in a COVID-19 patient, with asymptomatic history, occurred after swab negativization
Authors: Del Nonno Franca , Colombo Daniele , Nardacci Roberta , Falasca Laura
Published: January 2021

Background

A considerable number of SARS-CoV-2 infected individuals could be asymptomatic and don’t need medical treatment. The clinical spectrum of SARS-CoV-2 infection ranges from asymptomatic cases, medium-intensity forms with mild to moderate symptoms, to severe ones with bilateral pneumonia and respiratory distress. In cases with severe presentation of SARS-CoV-2 infection, the induction of hypercoagulability is one of the pathophysiological mechanism that can contribute to death.

Case presentation

Here, we reported autoptic evidences of thrombotic pulmonary arterial fatal lesions in an asymptomatic COVID-19 patient, after swab negativization. Whole body complete post-mortem examination was performed, showing the presence of a large thrombus occluding the main pulmonary artery that was the cause of death. Histopathological analysis showed heterogeneous pattern of pathological changes in the lung tissue with numerous vascular thrombi, inflammatory cardiomyopathy and other histopathological modifications in kidneys, spleen and liver.

Conclusions

This study provides evidences that also asymptomatic patients may be at risk to develop thrombotic complications. An appropriate diagnostic screening for thrombotic complications and the early treatment recommendations of antithrombotic drugs could represent an important topic even in asymptomatic individuals.
Approaches to motivate physicians and nurses in low- and middle-income countries: a systematic literature review
Authors: Gupta Jaya , Patwa Mariya C. , Khuu Angel , Creanga Andreea A.
Published: January 2021

Poor health worker motivation, and the resultant shortages and geographic imbalances of providers, impedes the provision of quality care in low- and middle-income countries (LMICs). This systematic review summarizes the evidence on interventions used to motivate health workers in LMICs. A standardized keyword search strategy was employed across five databases from September 2007 -September 2017. Studies had to meet the following criteria: original study; doctors and/or nurses as target population for intervention(s); work motivation as study outcome; study design with clearly defined comparison group; categorized as either a supervision, compensation, systems support, or lifelong learning intervention; and conducted in a LMIC setting. Two independent reviewers screened 3845 titles and abstracts and, subsequently, reviewed 269 full articles. Seven studies were retained from China (n = 1), Ghana (n = 2), Iran (n = 1), Mozambique (n = 1), and Zambia (n = 2). Study data and risk of bias were extracted using a standardized form. Though work motivation was the primary study outcome, four studies did not provide an outcome definition and five studies did not describe use of a theoretical framework in the ascertainment. Four studies used a randomized trial—group design, one used a non-randomized trial—group design, one used a cross-sectional design, and one used a pretest–posttest design. All three studies that found a significant positive effect on motivational outcomes had a supervision component. Of the three studies that found no effects on motivation, two were primarily compensation interventions and the third was a systems support intervention. One study found a significant negative effect of a compensation intervention on health worker motivation. In conducting this systematic review, we found there is limited evidence on successful interventions to motivate health workers in LMICs. True effects on select categories of health workers may have been obscured given that studies included health workers with a wide range of social and professional characteristics. Robust studies that use validated and culturally appropriate tools to assess worker motivation are greatly needed in the Sustainable Development Goals era.
Becoming a resident in a high demanded medical specialty: an unequal race? Evidence from the Spanish resident market
Authors: Rodriguez Santana Idaira
Published: January 2021

Background

Gender occupational segregation in medicine is associated with several undesired consequences such as earnings disparity, shortages of specialists or lower quality of care among others. This paper focuses on the persistent gender gap observed in the most popular specialties of the Spanish resident market. In particular, it explores the role of the specialty allocation system in perpetuating the occupational segregation. For that purpose, this paper studies the effect of a policy change in the ranking system that determines doctors’ specialty choice order. The change increased the competitiveness of the process by increasing the weight of an entry examination from 75% to 90%, in detriment of doctors’ grade point average that decreased from 25% to 10%. Findings from previous literature suggest that that male and female doctors might have reacted differently to the increased competitiveness of the process.

Methods

Data come from administrative records of doctors’ specialty choices for the years 2013 and 2015 and they are used to compute the difference between doctors’ pre and post-change ranking positions. Then, differences in the distribution of rank differences between male and female doctors are tested by means of parametric (T-test) and non-parametric (Wilcoxon rank) approaches.

Results

Results show that the policy change has overall favoured male doctors. On average, female doctors lose ranking positions, with respect to the position they would have achieved with the old weights, whilst male doctors gain positions. The differences are more pronounced in the top half of the ranking distribution, meaning that female doctors on average have reduced their probability of accessing the most demanded specialties.

Conclusions

The objective of the policy was the enhancement of the prospects of Spanish-graduate doctors with respect to international graduates by giving more weight to the less prone to bias examination scores. Nonetheless, the change have had the unintended consequence of reducing the probability of female doctors accessing highly demanded specialties and thus exacerbating the gender gap. The allocation system needs revision to make it accountable for the actual role of doctors in society.
Interplaying role of healthcare activist and homemaker: a mixed-methods exploration of the workload of community health workers (Accredited Social Health Activists) in India
Authors:   for the RESPIRE collaboration, Kawade Anand , Gore Manisha , Lele Pallavi , Chavan Uddhavi , Pinnock Hilary , Smith Pam , Juvekar Sanjay
Published: January 2021

Background

Globally, community health workers (CHWs) are integral contributors to many health systems. In India, Accredited Social Health Activists (ASHAs) have been deployed since 2005. Engaged in multiple health care activities, they are a key link between the health system and population. ASHAs are expected to participate in new health programmes prompting interest in their current workload from the perspective of the health system, community and their family.

Methods

This mixed-methods design study was conducted in rural and tribal Primary Health Centers (PHCs), in Pune district, Western Maharashtra, India. All ASHAs affiliated with these PHCs were invited to participate in the quantitative study, those agreeing to contribute in-depth interviews (IDI) were enrolled in an additional qualitative study. Key informants’ interviews were conducted with the Auxiliary Nurse Midwife (ANM), Block Facilitators (BFF) and Medical Officers (MO) of the same PHCs. Quantitative data were analysed using descriptive statistics. Qualitative data were analysed thematically.

Results

We recruited 67 ASHAs from the two PHCs. ASHAs worked up to 20 h/week in their village of residence, serving populations of approximately 800–1200, embracing an increasing range of activities, despite a workload that contributed to feelings of being rushed and tiredness. They juggled household work, other paid jobs and their ASHA activities. Practical problems with travel added to time involved, especially in tribal areas where transport is lacking. Their sense of benefiting the community coupled with respect and recognition gained in village brought happiness and job satisfaction. They were willing to take on new tasks. ASHAs perceived themselves as ‘voluntary community health workers’ rather than as ‘health activists”.

Conclusions

ASHAs were struggling to balance their significant ASHA work and domestic tasks. They were proud of their role as CHWs and willing to take on new activities. Strategies to recruit, train, skills enhancement, incentivise, and retain ASHAs, need to be prioritised. Evolving attitudes to the advantages/disadvantages of current voluntary status and role of ASHAs need to be understood and addressed if ASHAs are to be remain a key component in achieving universal health coverage in India.
Health provider perspectives on the implementation of the same-day-ART initiation policy in the Gauteng province of South Africa
Authors: Onoya Dorina , Mokhele Idah , Sineke Tembeka , Mngoma Bulelwa , Moolla Aneesa , Vujovic Marnie , Bor Jacob , Langa Jonas , Fox Matthew P.
Published: January 2021

Background

In September 2016, South Africa (SA) began implementing the universal-test-and-treat (UTT) policy in hopes of attaining the UNAIDS 90-90-90 targets by 2020. The SA National Department of Health provided a further directive to initiate antiretroviral therapy (ART) on the day of HIV diagnosis in September 2017. We conducted a qualitative study to determine the progress in implementing UTT and examine health providers' perspectives on the implementation of the same-day initiation (SDI) policy, six months after the policy change.

Methods

We conducted in-depth interviews with three professional nurses, and four HIV lay counsellors of five primary health clinics in the Gauteng province, between October and December 2017. In September 2018, we also conducted a focus group discussion with ten professional nurses/clinic managers from ten clinic facilities. The interviews and focus groups covered the adoption and implementation of UTT and SDI policies. Interviews were conducted in English, Sotho or Zulu and audio-recorded with participant consent. Audio-recordings were transcribed verbatim, translated to English and analysed thematically using NVivo 11.

Results

The data indicates inconsistencies across facilities and incongruities between counsellor and nursing provider perspectives regarding the SDI policy implementation. While nurses highlighted the clinical benefits of early ART initiation, they expressed concerns that immediate ART may be overwhelming for some patients, who may be unprepared and likely to disengage from care soon after the initial acceptance of ART. Accordingly, the SDI implementation was slow due to limited patient demand, provider ambivalence to the policy implementations, as well as challenges with infrastructure and human resources. The process for assessing patient readiness was poorly defined by health providers across facilities, inconsistent and counsellor dependent. Providers were also unclear on how to ensure that patients who defer treatment return for ongoing counselling.

Conclusions

Our results highlight important gaps in the drive to achieve the ART initiation target and demonstrate the need for further engagement with health care providers around the implementation of same-day ART initiation, particularly with regards to infrastructural/capacity needs and the management of patient readiness for lifelong ART on the day of HIV diagnosis. Additionally, there is a need for improved promotion of the SDI provision both in health care settings and in media communications to increase patient demand for early and lifelong ART.
Generalised cost-effectiveness analysis of 159 health interventions for the Ethiopian essential health service package
Authors: Eregata Getachew Teshome , Hailu Alemayehu , Stenberg Karin , Johansson Kjell Arne , Norheim Ole Frithjof , Bertram Melanie Y.
Published: January 2021

Background

Cost effectiveness was a criterion used to revise Ethiopia’s essential health service package (EHSP) in 2019. However, there are few cost-effectiveness studies from Ethiopia or directly transferable evidence from other low-income countries to inform a comprehensive revision of the Ethiopian EHSP. Therefore, this paper reports average cost-effectiveness ratios (ACERs) of 159 health interventions used in the revision of Ethiopia’s EHSP.

Methods

In this study, we estimate ACERs for 77 interventions on reproductive maternal neonatal and child health (RMNCH), infectious diseases and water sanitation and hygiene as well as for 82 interventions on non-communicable diseases. We used the standardised World Health Organization (WHO) CHOosing Interventions that are cost effective methodology (CHOICE) for generalised cost-effectiveness analysis. The health benefits of interventions were determined using a population state-transition model, which simulates the Ethiopian population, accounting for births, deaths and disease epidemiology. Healthy life years (HLYs) gained was employed as a measure of health benefits. We estimated the economic costs of interventions from the health system perspective, including programme overhead and training costs. We used the Spectrum generalised cost-effectiveness analysis tool for data analysis. We did not explicitly apply cost-effectiveness thresholds, but we used US$100 and $1000 as references to summarise and present the ACER results.

Results

We found ACERs ranging from less than US$1 per HLY gained (for family planning) to about US$48,000 per HLY gained (for treatment of stage 4 colorectal cancer). In general, 75% of the interventions evaluated had ACERs of less than US$1000 per HLY gained. The vast majority (95%) of RMNCH and infectious disease interventions had an ACER of less than US$1000 per HLY while almost half (44%) of non-communicable disease interventions had an ACER greater than US$1000 per HLY.

Conclusion

The present study shows that several potential cost-effective interventions are available that could substantially reduce Ethiopia’s disease burden if scaled up. The use of the World Health Organization’s generalised cost-effectiveness analysis tool allowed us to rapidly calculate country-specific cost-effectiveness analysis values for 159 health interventions under consideration for Ethiopia’s EHSP.
Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge” (December 4th–5th, 2019, Naples, Italy)
Authors: Ascierto Paolo A. , Butterfield Lisa H. , Campbell Katie , Daniele Bruno , Dougan Michael , Emens Leisha A. , Formenti Silvia , Janku Filip , Khleif Samir N. , Kirchhoff Tomas , Morabito Alessandro , Najjar Yana , Nathan Paul , Odunsi Kunle , Patnaik Akash , Paulos Chrystal M. , Reinfeld Bradley I. , Skinner Heath D. , Timmerman John , Puzanov Igor
Published: January 2021

Over the last few years, numerous clinical trials and real-world experience have provided a large amount of evidence demonstrating the potential for long-term survival with immunotherapy agents across various malignancies, beginning with melanoma and extending to other tumours. The clinical success of immune checkpoint blockade has encouraged increasing development of other immunotherapies. It has been estimated that there are over 3000 immuno-oncology trials ongoing, targeting hundreds of disease and immune pathways. Evolving topics on cancer immunotherapy, including the state of the art of immunotherapy across various malignancies, were the focus of discussions at the Immunotherapy Bridge meeting (4–5 December, 2019, Naples, Italy), and are summarised in this report.
Multi-omic signatures of atherogenic dyslipidaemia: pre-clinical target identification and validation in humans
Authors: Olkowicz Mariola , Czyzynska-Cichon Izabela , Szupryczynska Natalia , Kostogrys Renata B. , Kochan Zdzislaw , Debski Janusz , Dadlez Michal , Chlopicki Stefan , Smolenski Ryszard T.
Published: January 2021

Background

Dyslipidaemia is a major risk factor for atherosclerosis and cardiovascular diseases. The molecular mechanisms that translate dyslipidaemia into atherogenesis and reliable markers of its progression are yet to be fully elucidated. To address this issue, we conducted a comprehensive metabolomic and proteomic analysis in an experimental model of dyslipidaemia and in patients with familial hypercholesterolemia (FH).

Methods

Liquid chromatography/mass spectrometry (LC/MS) and immunoassays were used to find out blood alterations at metabolite and protein levels in dyslipidaemic ApoE−/−/LDLR−/− mice and in FH patients to evaluate their human relevance.

Results

We identified 15 metabolites (inhibitors and substrates of nitric oxide synthase (NOS), low-molecular-weight antioxidants (glutamine, taurine), homocysteine, methionine, 1-methylnicotinamide, alanine and hydroxyproline) and 9 proteins (C-reactive protein, proprotein convertase subtilisin/kexin type 9, apolipoprotein C-III, soluble intercellular adhesion molecule-1, angiotensinogen, paraoxonase-1, fetuin-B, vitamin K-dependent protein S and biglycan) that differentiated FH patients from healthy controls. Most of these changes were consistently found in dyslipidaemic mice and were further amplified if mice were fed an atherogenic (Western or low-carbohydrate, high-protein) diet.

Conclusions

The alterations highlighted the involvement of an immune-inflammatory response system, oxidative stress, hyper-coagulation and impairment in the vascular function/regenerative capacity in response to dyslipidaemia that may also be directly engaged in development of atherosclerosis. Our study further identified potential biomarkers for an increased risk of atherosclerosis that may aid in clinical diagnosis or in the personalized treatment.
Effect of a novel functional tomato sauce (OsteoCol) from vine-ripened tomatoes on serum lipids in individuals with common hypercholesterolemia: tomato sauce and hypercholesterolemia
Authors: Ferro Yvelise , Mazza Elisa , Angotti Elvira , Pujia Roberta , Mirarchi Angela , Salvati Maria Antonietta , Terracciano Rosa , Savino Rocco , Romeo Stefano , Scuteri Antonio , Mare Rosario , Costanzo Francesco Saverio , Pujia Arturo , Montalcini Tiziana
Published: January 2021

Background

Most studies focused on the benefits of lycopene on serum lipids but no studies have been specifically designed to assess the role of a tomato sauce from vine-ripened tomatoes on patients affected by polygenic hypercholesterolemia. The aim of this study was to compare the lipid-lowering effect of a novel functional tomato sauce with a well-known functional food with a lipid-lowering effect, i.e. a sterol-enriched yogurt.

Methods

In this cross-over study, we evaluated a population of 108 ambulatory patients affected by polygenic hypercholesterolemia of both gender, who were allocated to a tomato sauce (namely OsteoCol) 150 ml/day or a sterol-enriched yogurt (containing sterols 1.6 g/die) treatment, for 6 weeks. Carotenoids content was 3.5 mg per gram of product. We measured serum lipids and creatinine and transaminases at basal and follow-up visit.

Results

A total of 91 subjects completed the protocol. A significant difference in LDL-cholesterol change was found between participants taking yogurt, tomato sauce (high adherence) and tomato sauce (low adherence) (− 16; − 12; + 8 mg/dl respectively; p < 0.001). We found a greater LDL-cholesterol reduction in the participants with a basal LDL-cholesterol more than 152 mg/dl (15% for sterol-enriched yogurt and 12% for tomato sauce at high adherence).

Conclusion

A novel functional tomato sauce from vine-ripened tomatoes compares favourably with a commercialised sterol-enriched yogurt in term of absolute LDL-cholesterol change. Intake of a tomato sauce with a high carotenoid content may support treatment of patients affected by common hypercholesterolemia. The present study has various limitations. The presence of other dietary components, which may have influenced the results, cannot be ruled out. Of course, these results cannot be extrapolated to other populations. Furthermore, there was a low adherence rate in the tomato sauce group. Moreover, we did not report serum carotenoids data.

Trial registration: ID: 13244115 on the ISRCTN registry, retrospectively registered in 2019-5-14. URL:http://www.isrctn.com/ISRCTN13244115
Effects of time-restricted feeding in weight loss, metabolic syndrome and cardiovascular risk in obese women
Authors: Schroder Jéssica D. , Falqueto Hugo , Mânica Aline , Zanini Daniela , de Oliveira Tácio , de Sá Clodoaldo A. , Cardoso Andréia Machado , Manfredi Leandro Henrique
Published: January 2021

Background

The increasing prevalence of overweight and obesity among the worldwide population has been associated with a range of adverse health consequences such as Type 2 diabetes and cardiovascular diseases. The metabolic syndrome (MetS) is a cluster of cardiometabolic abnormalities that occur more commonly in overweight individuals. Time-restricted feeding (TRF) is a dietary approach used for weight loss and overall health. TRF may be an option for those subjects who struggle with extreme restriction diets with foods that generally do not belong to an individual's habits.

Objective

The purpose of this study was to determine the effect of TRF on body composition and the association of weight loss with metabolic and cardiovascular risks in obese middle-aged women.

Methods

A non-randomized controlled clinical trial was performed over 3 months in obese women (TRF group, n = 20, BMI 32.53 ± 1.13 vs. Control n = 12, BMI 34.55 ± 1.20). The TRF protocol adopted was 16 h without any energy intake followed by 8 h of normal food intake.

Main outcomes and measures

Anthropometric measurements, body composition, blood biomarkers, cardiovascular risk in 30 years (CVDRisk30y), and quality of life were evaluated at baseline and after the 3 months.

Results

TRF was effective in reducing weight (~ 4 kg), BMI, % of body fat (%BF), waist circumference from baseline without changes in blood biomarkers associated with MetS. TRF promoted a reduction in CVDRisk30y (12%) wich was moderately correlated with %BF (r = 0.62, n = 64, p < 0.001) and %MM (r = − 0.74, n = 64, p < 0.001).

Conclusions

TRF protocol reduces body weight without changes in biomarkers related to MetS. In addition, the anthropometric evaluation that predicts %BF and %MM could be used as an approach to follow individuals engaged in the TRF regimen since they correlate with cardiovascular risk.
Three hematologic/immune system-specific expressed genes are considered as the potential biomarkers for the diagnosis of early rheumatoid arthritis through bioinformatics analysis
Authors: Cheng Qi , Chen Xin , Wu Huaxiang , Du Yan
Published: January 2021

Background

Rheumatoid arthritis (RA) is the most common chronic autoimmune connective tissue disease. However, early RA is difficult to diagnose due to the lack of effective biomarkers. This study aimed to identify new biomarkers and mechanisms for RA disease progression at the transcriptome level through a combination of microarray and bioinformatics analyses.

Methods

Microarray datasets for synovial tissue in RA or osteoarthritis (OA) were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified by R software. Tissue/organ-specific genes were recognized by BioGPS. Enrichment analyses were performed and protein–protein interaction (PPI) networks were constructed to understand the functions and enriched pathways of DEGs and to identify hub genes. Cytoscape was used to construct the co-expressed network and competitive endogenous RNA (ceRNA) networks. Biomarkers with high diagnostic value for the early diagnosis of RA were validated by GEO datasets. The ggpubr package was used to perform statistical analyses with Student’s t-test.

Results

A total of 275 DEGs were identified between 16 RA samples and 10 OA samples from the datasets GSE77298 and GSE82107. Among these DEGs, 71 tissue/organ-specific expressed genes were recognized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that DEGs are mostly enriched in immune response, immune-related biological process, immune system, and cytokine signal pathways. Fifteen hub genes and gene cluster modules were identified by Cytoscape. Eight haematologic/immune system-specific expressed hub genes were verified by GEO datasets. GZMA, PRC1, and TTK may be potential biomarkers for diagnosis of early RA. NEAT1-miR-212-3p/miR-132-3p/miR-129-5p-TTK, XIST-miR-25-3p/miR-129-5p-GZMA, and TTK_hsa_circ_0077158- miR-212-3p/miR-132-3p/miR-129-5p-TTK might be potential RNA regulatory pathways to regulate the disease progression of early RA.

Conclusions

This work identified three haematologic/immune system-specific expressed genes, namely, GZMA, PRC1, and TTK, as potential biomarkers for the early diagnosis and treatment of RA and provided insight into the mechanisms of disease development in RA at the transcriptome level. In addition, we proposed that NEAT1-miR-212-3p/miR-132-3p/miR-129-5p-TTK, XIST-miR-25-3p/miR-129-5p-GZMA, and TTK_hsa_circ_0077158-miR-212-3p/miR-132-3p/miR-129-5p-TTK are potential RNA regulatory pathways that control disease progression in early RA.
Suicidal risk and resilience in juvenile fibromyalgia syndrome: a cross-sectional cohort study
Authors: Gmuca Sabrina , Sonagra Maitry , Xiao Rui , Miller Kimberly S. , Thomas Nina H. , Young Jami F. , Weiss Pamela F. , Sherry David D. , Gerber Jeffrey S.
Published: January 2021

Background

To characterize suicidality among youth with juvenile fibromyalgia syndrome (JFMS) receiving treatment from pediatric rheumatologists at a tertiary care center in order to determine the prevalence of suicidality in JFMS and to explore risk factors for persistent suicidal ideation.

Methods

We performed a cross-sectional cohort study of children 12–17 years old with JFMS seen in a specialty pediatric rheumatology pain clinic from 7/2017–9/2019. All subjects completed patient-reported outcomes measures, complemented by retrospective chart review. Subjects who endorsed item 8 on the Children’s Depression Inventory, 2nd Edition (CDI-2) were categorized as endorsing suicidal ideation. We assessed for differences between the suicidal and non-suicidal patients using Wilcoxon-rank sum test. Logistic regression modeling was performed to identify psychosocial factors associated with suicidality.

Results

Of the 31 subjects, more than one-quarter endorsed suicidality. Nearly 90% of teens with suicidal ideation were established in outpatient counseling. In bivariate analyses, suicidality was associated with lower resilience and greater depression and anxiety (allp < 0.05). Pain intensity trended towards a statistically significant positive association (OR: 1.16 [0.99–1.37];p = 0.06). Lower resilience was independently associated with suicidality (OR: 0.90 [95% CI: 0.82–0.98];p < 0.02).

Conclusions

Suicidality was prevalent among youth with JFMS and persistent despite concurrent receipt of mental health services. Higher patient-level resilience was independently associated with a reduced odds of suicidality. Future work should examine the role of resilience training on reducing psychological distress and mitigating the risk of suicidality in JFMS.
Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial
Authors: Alexeeva Ekaterina , Horneff Gerd , Dvoryakovskaya Tatyana , Denisova Rina , Nikishina Irina , Zholobova Elena , Malievskiy Viktor , Santalova Galina , Stadler Elena , Balykova Larisa , Spivakovskiy Yuriy , Kriulin Ivan , Alshevskaya Alina , Moskalev Andrey
Published: January 2021

Background

Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease.

Methods

A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit.

Results

By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients.

Conclusions

Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.
mGlu3 receptor regulates microglial cell reactivity in neonatal rats
Authors: Zinni Manuela , Mairesse Jérôme , Pansiot Julien , Fazio Francesco , Iacovelli Luisa , Antenucci Nico , Orlando Rosamaria , Nicoletti Ferdinando , Vaiman Daniel , Baud Olivier
Published: January 2021

Background

Perinatal inflammation is a key factor of brain vulnerability in neonates born preterm or with intra-uterine growth restriction (IUGR), two leading conditions associated with brain injury and responsible for neurocognitive and behavioral disorders. Systemic inflammation is recognized to activate microglia, known to be the critical modulators of brain vulnerability. Although some evidence supports a role for metabotropic glutamate receptor 3 (mGlu3 receptor) in modulation of neuroinflammation, its functions are still unknown in the developing microglia.

Methods

We used a double-hit rat model of perinatal brain injury induced by a gestational low-protein diet combined with interleukin-1β injections (LPD/IL-1β), mimicking both IUGR and prematurity-related inflammation. The effect of LPD/IL-1β on mGlu3 receptor expression and the effect of mGlu3 receptor modulation on microglial reactivity were investigated using a combination of pharmacological, histological, and molecular and genetic approaches.

Results

Exposure to LPD/IL-1β significantly downregulated Grm3 gene expression in the developing microglia. Both transcriptomic analyses and pharmacological modulation of mGlu3 receptor demonstrated its central role in the control of inflammation in resting and activated microglia. Microglia reactivity to inflammatory challenge induced by LPD/IL-1β exposure was reduced by an mGlu3 receptor agonist. Conversely, both specific pharmacological blockade, siRNA knock-down, and genetic knock-out of mGlu3 receptors mimicked the pro-inflammatory phenotype observed in microglial cells exposed to LPD/IL-1β.

Conclusions

Overall, these data show that Grm3 plays a central role in the regulation of microglial reactivity in the immature brain. Selective pharmacological activation of mGlu3 receptors may prevent inflammatory-induced perinatal brain injury.
Environmental noise stress disturbs commensal microbiota homeostasis and induces oxi-inflammmation and AD-like neuropathology through epithelial barrier disruption in the EOAD mouse model
Authors: Chi Huimin , Cao Wa , Zhang Ming , Su Donghong , Yang Honglian , Li Zhe , Li Chao , She Xiaojun , Wang Kun , Gao Xiujie , Ma Kefeng , Zheng Pengfang , Li Xiaofang , Cui Bo
Published: January 2021

Background

Both genetic factors and environmental hazards, including environmental noise stress, have been associated with gut microbiome that exacerbates Alzheimer’s disease (AD) pathology. However, the role and mechanism of environmental risk factors in early-onset AD (EOAD) pathogenesis remain unclear.

Methods

The molecular pathways underlying EOAD pathophysiology following environmental noise exposure were evaluated using C57BL/6 wild-type (WT) and APP/PS1 Tg mouse models. The composition differences in intestinal microbiota were analyzed by 16S rRNA sequencing and Tax4Fun to predict the metagenome content from sequencing results. An assessment of the flora dysbiosis-triggered dyshomeostasis of oxi-inflamm-barrier and the effects of the CNS end of the gut–brain axis was conducted to explore the underlying pathological mechanisms.

Results

Both WT and APP/PS1 mice showed a statistically significant relationship between environmental noise and the taxonomic composition of the corresponding gut microbiome. Bacterial-encoded functional categories in noise-exposed WT and APP/PS1 mice included phospholipid and galactose metabolism, oxidative stress, and cell senescence. These alterations corresponded with imbalanced intestinal oxidation and anti-oxidation systems and low-grade systemic inflammation following noise exposure. Mechanistically, axis-series experiments demonstrated that following noise exposure, intestinal and hippocampal tight junction protein levels reduced, whereas serum levels of inflammatory mediator were elevated. Regarding APP/PS1 overexpression, noise-induced abnormalities in the gut–brain axis may contribute to aggravation of neuropathology in the presymptomatic stage of EOAD mice model.

Conclusion

Our results demonstrate that noise exposure has deleterious effects on the homeostasis of oxi-inflamm-barrier in the microbiome–gut–brain axis. Therefore, at least in a genetic context, chronic noise may aggravate the progression of EOAD.
Differential neurovirulence of Usutu virus lineages in mice and neuronal cells
Authors: Clé Marion , Constant Orianne , Barthelemy Jonathan , Desmetz Caroline , Martin Marie France , Lapeyre Lina , Cadar Daniel , Savini Giovanni , Teodori Liana , Monaco Federica , Schmidt-Chanasit Jonas , Saiz Juan-Carlos , Gonzales Gaëlle , Lecollinet Sylvie , Beck Cécile , Gosselet Fabien , Van de Perre Philippe , Foulongne Vincent , Salinas Sara , Simonin Yannick
Published: January 2021

Background

Usutu virus (USUV) is an emerging neurotropic arthropod-borne virus recently involved in massive die offs of wild birds predominantly reported in Europe. Although primarily asymptomatic or presenting mild clinical signs, humans infected by USUV can develop neuroinvasive pathologies (including encephalitis and meningoencephalitis). Similar to other flaviviruses, such as West Nile virus, USUV is capable of reaching the central nervous system. However, the neuropathogenesis of USUV is still poorly understood, and the virulence of the specific USUV lineages is currently unknown. One of the major complexities of the study of USUV pathogenesis is the presence of a great diversity of lineages circulating at the same time and in the same location.

Methods

The aim of this work was to determine the neurovirulence of isolates from the six main lineages circulating in Europe using mouse model and several neuronal cell lines (neurons, microglia, pericytes, brain endothelial cells, astrocytes, and in vitro Blood-Brain Barrier model).

Results

Our results indicate that all strains are neurotropic but have different virulence profiles. The Europe 2 strain, previously described as being involved in several clinical cases, induced the shortest survival time and highest mortality in vivo and appeared to be more virulent and persistent in microglial, astrocytes, and brain endothelial cells, while also inducing an atypical cytopathic effect. Moreover, an amino acid substitution (D3425E) was specifically identified in the RNA-dependent RNA polymerase domain of the NS5 protein of this lineage.

Conclusions

Altogether, these data show a broad neurotropism for USUV in the central nervous system with lineage-dependent virulence. Our results will help to better understand the biological and epidemiological diversity of USUV infection.