bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclooxygenase-1 mediates neuroinflammation and neurotoxicity in a mouse model of retinitis pigmentosa
Authors: Yang Wei , Xiong Guoyin , Lin Bin
Published: October 2020

Background

Retinitis pigmentosa (RP) is a group of inherited eye disorders with progressive degeneration of photoreceptors in the retina, ultimately leading to partial or complete blindness. The mechanisms underlying photoreceptor degeneration are not yet completely understood. Neuroinflammation is reported to play a pathological role in RP. However, the mechanisms that trigger neuroinflammation remain largely unknown. To address this question, we investigated the role of cyclooxygenase-1 (COX-1), a key enzyme in the conversion of arachidonic acid to proinflammatory prostaglandins, in the rd10 mouse model of RP.

Methods

We backcrossed COX-1 knockout mice (COX-1−/−) onto the rd10 mouse model of RP and investigated the impact of COX-1 deletion on neuroinflammation in the resulting COX-1−/−/rd10 mouse line, using a combination of immunocytochemistry, flow cytometry, qPCR, ELISA, and a series of simple visual tests.

Results

We found that genetic ablation or pharmacological inhibition of COX-1 alleviated neuroinflammation and subsequently preserved retinal photoreceptor and function and visual performance in rd10 mice. Moreover, we observed that the pharmacological inhibition of the prostaglandin E2 (PGE2) EP2 receptors largely replicated the beneficial effects of COX-1 deletion, suggesting that EP2 receptor was a critical downstream effector of COX-1-mediated neurotoxicity in rd10 mice.

Conclusion

Our data suggest that the COX-1/PGE2/EP2 signaling pathway was partly responsible for significantly increased neuroinflammation and disease progression in rd10 mice, and that EP2 receptor could be targeted therapeutically to block the pathological activity of COX-1 without inducing any potential side effects in treating RP patients.
Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents
Authors: Khadke Sumanth , Ahmed Nayla , Ahmed Nausheen , Ratts Ryan , Raju Shine , Gallogly Molly , de Lima Marcos , Sohail Muhammad Rizwan
Published: October 2020

Background

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage.

Discussion

We reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS). COVID-19 illness encompasses three main phases. In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling. It effectively blunts an early (IFN) response allowing unchecked viral replication. Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak. Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms, persistent fever, and hemodynamic instability. Important cytokines involved in this phase are interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. This is typically followed by a recovery phase with production of antibodies against the virus. We summarize published data regarding virus-host interactions, key immunological mechanisms responsible for virus-associated CRS, and potential opportunities for therapeutic interventions.

Conclusion

Evidence regarding SARS-CoV-2 epidemiology and pathogenesis is rapidly evolving. A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and other therapeutic interventions.
Diesel exhaust particle exposure reduces expression of the epithelial tight junction protein Tricellulin
Authors: Smyth Timothy , Veazey Janelle , Eliseeva Sophia , Chalupa David , Elder Alison , Georas Steve N.
Published: October 2020

Background

While exposure to diesel exhaust particles has been linked to aberrant immune responses in allergic diseases such as asthma, little attention has been paid to their effects on the airway epithelial barrier. In this study, we sought to determine the effect of diesel exhaust exposure on airway epithelial barrier function and composition using in vitro and in vivo model systems.

Methods

16HBE14o- human bronchial epithelial cells were grown on collagen coated Transwell inserts and exposed to 5 to 50 μg/cm2SRM 2975 diesel particulate matter (DEP) suspended in cell culture medium or vehicle controls. Changes in barrier function were assessed by measuring transepithelial electrical resistance (TEER) and permeability to 4 kDa FITC Dextran. Neonatal BALB/c mice were exposed to aerosolized DEP (255 ± 89 μg/m3; 2 h per day for 5 days) and changes in the tight junction protein Tricellulin were assessed 2 weeks post exposure.

Results

A six-hour incubation of epithelial cells with diesel exhaust particles caused a significant concentration-dependent reduction in epithelial barrier integrity as measured by decreased TEER and increased permeability to 4 kDa FITC-Dextran. This reduction in epithelial barrier integrity corresponded to a significant reduction in expression of the tight junction protein Tricellulin. siRNA mediated knockdown of Tricellulin recapitulated changes in barrier function caused by DEP exposure. Neonatal exposure to aerosolized DEP caused a significant reduction in lung Tricellulin 2 weeks post exposure at both the protein and mRNA level.

Conclusion

Short term exposure to DEP causes a significant reduction in epithelial barrier integrity through a reduction in the tight junction protein Tricellulin. Neonatal exposure to aerosolized DEP caused a significant and sustained reduction in Tricellulin protein and mRNA in the lung, suggesting that early life exposure to inhaled DEP may cause lasting changes in airway epithelial barrier function.
Investigation of the differences between the medical personnel’s and general population’s view on the doctor-patient relationship in China by a cross-sectional survey
Authors: Sang Tianqing , Zhou Hongli , Li Muhan , Li Wenting , Shi Haibo , Chen Haibin , Zhou Hongguang
Published: October 2020

Background

Due to economic development and an increase in the aging population, the demand for medical resources is increasing. A good doctor-patient relationship (DPR) can optimize patients’ medical experience and improve treatment efficiency. The DPR, however, is currently in crisis in China. To explore ways to improve DPR, this study assessed the views on the status of the DPR, medical services, and the general situation of medical work among medical personnel (MP) and the general population (GP).

Methods

This cross-sectional study, conducted between December 2019 and March 2020, targeted the MP and the GP in Nanjing City, Jiangsu Province, and Zhengzhou City, Henan Province. A total of 154 MP and 329 GP answered a self-administered questionnaire through Questionnaire Star and WeChat apps. Wilcoxon’s Sign Rank Test, Chi-square test, and frequency distributions and percentages were used to process the data.

Results

Only 11.04% of the MP and 14.89% of the GP believed that the current DPR was harmonious. Moreover, 54.55% of the MP and 71.12% of the GP believed that the medical industry was a service industry. While 14.29% of the MP and 64.44% of the GP thought medical staff earned high salaries, 19.48% of the MP and 47.11% of the GP wanted their children to be in the medical industry. The recognition of the current status of the DPR did not affect the GP’s preference for their children’s practice (p < 0.05). Most MPs hoped to improve salaries (40.26%), followed by safety (17.53%) and social status (12.99%); only 8.44% of the MP wanted to improve the DPR.

Conclusion

The MP’s and GP’s views on the current status of DPR, the importance of medical service attitudes, and the general sense of the medical industry were similar. However, there was a significant difference in the perception of the nature of medical services and the income of the people employed in the medical industry between the two groups. Balancing the expectations of patients in the medical industry and increasing public awareness of the actual situation in the medical industry may be a feasible way to improve the DPR.
Estimating a treatment effect on recidivism for correctional multiple component treatment for people in prison with an alcohol use disorder in England
Authors: Sondhi Arun , Leidi Alessandro , Best David
Published: October 2020

Background

There is an emerging literature on the impact of correctional substance abuse treatment (SAT) on reoffending for people in prison with substance misuse issues. This study estimates a pathway effect for people in prison receiving multiple component treatments for an alcohol use disorder (AUD) to reduce reoffending by applying treatment effect estimation techniques for observational studies. Treatment groups comprised pharmacological treatments, psychosocial interventions (PSIs) and interventions that incorporate Risk Need Responsivity (RNR) programming. RNR compliant treatment matches treatment dose to the risk of reoffending, targets criminogenic need and is tailored to a person’s learning style.

Methods

Multiple treatment effect estimators are provided for people in prison diagnosed with an AUD in England when compared to a derived control group for: Pharmacological treatment only; RNR compliant treatment and PSIs.

Results

The outcomes for RNR compliant treatment suggest a lower recidivism rate compared to the control group. Pharmacological only treatment results in a statistically significant higher level of reoffending relative to the control group.

Conclusions

The creation of a universal system of ‘equivalence of care’ framed within a public health context in English correctional SAT may have had an unintended consequence of diluting approaches that reduce recidivism. There is an opportunity to develop an integrated, cross-disciplinary model for correctional SAT that unites public health and RNR compliant approaches.
Strategies for effective dissemination of research to United States policymakers: a systematic review
Authors: Ashcraft Laura Ellen , Quinn Deirdre A. , Brownson Ross C.
Published: October 2020

Background

Research has the potential to influence US social policy; however, existing research in this area lacks a coherent message. The Model for Dissemination of Research provides a framework through which to synthesize lessons learned from research to date on the process of translating research to US policymakers.

Methods

The peer-reviewed and grey literature was systematically reviewed to understand common strategies for disseminating social policy research to policymakers in the United States. We searched Academic Search Premier, PolicyFile, SocINDEX, Social Work Abstracts, and Web of Science from January 1980 through December 2019. Articles were independently reviewed and thematically analyzed by two investigators and organized using the Model for Dissemination of Research.

Results

The search resulted in 5225 titles and abstracts for inclusion consideration. 303 full-text articles were reviewed with 27 meeting inclusion criteria. Common sources of research dissemination included government, academic researchers, the peer reviewed literature, and independent organizations. The most frequently disseminated research topics were health-related, and legislators and executive branch administrators were the most common target audience. Print materials and personal communication were the most common channels for disseminating research to policymakers. There was variation in dissemination channels by level of government (e.g., a more formal legislative process at the federal level compared with other levesl). Findings from this work suggest that dissemination is most effective when it starts early, galvanizes support, uses champions and brokers, considers contextual factors, is timely, relevant, and accessible, and knows the players and process.

Conclusions

Effective dissemination of research to US policymakers exists; yet, rigorous quantitative evaluation is rare. A number of cross-cutting strategies appear to enhance the translation of research evidence into policy.

Registration

Not registered.
The strategies of perioperative management in orthopedic department during the pandemic of COVID-19
Authors: Zeng Hui , Li Guoqing , Weng Jian , Xiong Ao , Xu Chang , Yang Yifei , Wang Deli
Published: October 2020

Background

Coronavirus disease 2019 (COVID-19) has broken out and spread rapidly nationwide at the beginning of 2020, which has brought huge impacts to people and work. The current situation of prevention and control is severe and urges guidance for clinicians, especially for medical systems. In the hope of providing a reference and recommendation for the prevention and control of the COVID-19, we carried out research to improve the quality of patient care and prevention during this epidemic.

Methods

All of the staff were trained rapidly to master personal protection in our department. We reviewed the patients’ discharged records who underwent surgery in our department during January 1 to March 1, 2019, and January 1 to March 1, 2020. The management of the surgery patients and flow charts were described and analyzed. Post-operation outcomes of the patients include duration, complications, surgical site infection (SSI), system infection, re-operation, and mortality. Both chi-squared test and Student’s t test were performed to determine the relationship between the two periods in terms of post-operation outcomes.

Results

Descriptive statistics analysis revealed that demographic of the patients between the two periods is similar. We had benefited from the strict flowcharts, smart robot, and protection equipment during the perioperative managements for orthopedic patients. With the help of the strict flow charts and smart equipment, post-operation outcomes of the patients revealed that the rates of the complications and re-operation had been reduced significantly (p < 0.05), while duration of operation, SSI, and system infection had no significant difference between two periods (p > 0.05). No patient and staff caught COVID-19 infection or mortality during the epidemic.

Conclusions

Our study indicated that medical quality and efficiency were affected little with the help of strategies described above during the epidemic, which could be a reference tool for medical staff in routine clinical practice for admission of patients around the world. What is more, the provided strategies, which may evolve over time, could be used as empirical guidance and reference for orthopedic peers to get through the pandemic and ensure the normal operation of the hospital.
Overweight and aging increase the risk of atrial fibrillation after cardiac surgery independently of left atrial size and left ventricular ejection fraction
Authors: Stefàno Pier Luigi , Bugetti Marco , Del Monaco Guido , Popescu Gloria , Pieragnoli Paolo , Ricciardi Giuseppe , Perrotta Laura , Checchi Luca , Rondine Roberto , Bevilacqua Sergio , Fumagalli Carlo , Marchionni Niccolò , Michelucci Antonio
Published: October 2020

Background

Body mass index (BMI), age, left atrium (LA) dimension and left ventricular ejection fraction (LVEF) have been linked to post-operative atrial fibrillation (POAF) after cardiac surgery. The aim of this study was to better define the role of these risk factors.

Methods

This retrospective cohort study evaluated 249 patients (without prior atrial dysrhythmia) undergoing cardiac or aortic surgery. Prior to surgery, the following data were collected: age, BMI, LA diameter, LA area, LVEF, thyroid stimulating hormone (TSH), creatinine and the presence of arterial hypertension (AH) and diabetes. Intraoperative data such as operation time, total clamp time, cardiopulmonary bypass time, and presence of pericardial/pleural effusion were also collected. Only patients without pre- and post-surgery prophylactic anti-arrhythmic therapy were included.

Results

Patients with (N = 127, 51%) and without POAF (N = 122, 49%) were compared. No difference was observed for sex, LA diameter, LA area, LVEF, TSH, diabetes and use of ACE inhibitors or statins prior to intervention. Moreover, no difference was observed in terms of operation time, total clamp time, cardiopulmonary bypass time, and presence of pericardial/pleural effusion. However, patients with POAF were older (70.6 ± 10.7 vs. 60.4 ± 16.4 years, p = 0.001), had higher BMI (26.8 ± 4.5 vs. 24.9 ± 3.6 kg/m2, p = 0.001), higher baseline creatinine (1.06 ± 0.91 vs. 0.88 ± 0.32 mg/dL, p = 0.038) and a higher frequency of arterial hypertension (73.2% vs. 50%, p = 0.001) and Bentall procedure (24.4% vs. 9.8%, p = 0.023). Multivariate analysis showed that the only independent predictors of POAF were age (OR = 1.05, 95%CI 1.02–1.07, p = 0.001) and BMI (OR = 1.11 95%CI 1.03–1.2,p = 0.006).

Conclusions

These findings suggest that advanced age and a higher BMI are strong risk factors for POAF in patients without previous AF even in the presence of comparable LA dimensions and LVEF.
Optimising the mutation screening strategy in Marfan syndrome and identifying genotypes with more severe aortic involvement
Authors: Stengl Roland , Bors András , Ágg Bence , Pólos Miklós , Matyas Gabor , Molnár Mária Judit , Fekete Bálint , Csabán Dóra , Andrikovics Hajnalka , Merkely Béla , Radovits Tamás , Szabolcs Zoltán , Benke Kálmán
Published: October 2020

Background

Marfan syndrome (MFS) is a systemic connective tissue disorder with life-threatening manifestations affecting the ascending aorta. MFS is caused by dominant negative (DN) and haploinsufficient (HI) mutations of theFBN1gene. Our aim was to identify mutations of MFS patients with high detection rate and to investigate the use of a gene panel for patients with Marfanoid habitus. We also aimed to examine correlations between genotype and cardiovascular manifestations to predict “malignant” mutations.

Methods

136 individuals were enrolled. In the first phase, next-generation sequencing (NGS) and Sanger sequencing were performed for 57 patients to screen theFBN1gene, followed by multiplex ligation-dependent probe amplification (MLPA) in negative cases. For repeated negative results, NGS gene panel involving 9 genes was used. In the second phase, 79 patients were tested primarily with the same gene panel, negative samples were tested by MLPA.

Results

84 pathogenic mutations were detected, out of which 78 affectedFBN1, 6 non-FBN1mutations (2TGFB2, 1TGFBR2, 2TGFBR1, 1SMAD3) are associated with Loeys-Dietz syndrome (LDS). LDS patients had lower systemic score and they were younger, but their aortic involvement did not differ. MLPA detected 4 multi-exon deletions ofFBN1gene, which could not be identified by our first-step screening method. Aortic involvement (aortic dissection and/or dilation) did not differ significantly among HI and DN mutations (p = 0.061). Combined group of HI and DN mutations eliminating a disulphide-bonding cysteine (DN Cys) had significantly higher aortic involvement rate than DN mutations not eliminating a disulphide-bonding cysteine (DN non-Cys) (p < 0.001). Patients with DN Cys required significantly more aortic surgeries than HI and DN non-Cys mutations (p = 0.042 andp = 0.015, respectively).

Conclusions

Due to the relevant number of mutations affecting genes other thanFBN1, preferred approach for testing individuals with Marfanoid habitus is using a gene panel rather than single-gene analysis, followed by MLPA for negative samples. DN Cys and HI mutations should be considered as risk factors for aortic involvement. Genetic testing for patients with Marfanoid features and a systemic score under 7 is recommended, as LDS patients may have lower scores, but they may have severe cardiovascular manifestations.
Clinical features of genetically characterized types of hereditary angioedema with normal C1 inhibitor: a systematic review of qualitative evidence
Authors: Bork Konrad , Machnig Thomas , Wulff Karin , Witzke Guenther , Prusty Subhransu , Hardt Jochen
Published: October 2020

Background

Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) (HAEnCI) is associated with skin swellings, abdominal attacks, and the risk of asphyxia due to upper airway obstruction. Several different gene mutations linked to the HAE phenotype have been identified. Our aim was to qualitatively assess and describe the clinical differentiators of these genetically identified HAEnCI types. To achieve this, we performed a systematic literature review of patients with angioedema symptoms and a genetically confirmed diagnosis of an HAEnCI type.

Results

A systematic literature search, conducted in March 2020, returned 132 records, 43 of which describe patients with symptoms of angioedema and a genetically confirmed diagnosis of an HAEnCI type. Overall, this included 602 patient cases from 220 families. HAEnCI with a mutation in the coagulation factor XII gene (F12) (HAE-FXII) was diagnosed in 446 patients from 185 families (male:female ratio = 1:10). Estrogens (oral contraceptives, hormonal replacement therapy, and pregnancy) negatively impacted the course of disease in most female patients (252 of 277). Asphyxia occurred in 2 of 446 patients. On-demand and/or long-term prophylaxis treatment included C1-INH concentrates, icatibant, progestins, and tranexamic acid. HAEnCI with a specific mutation in the plasminogen gene (HAE-PLG) was diagnosed in 146 patients from 33 families (male:female ratio = 1:3). Estrogens had a negative influence on the course of disease in the minority of female patients (14 of 62). Tongue swelling was an important clinical feature. Asphyxia occurred in 3 of 146 patients. On-demand treatment with icatibant and C1-INH concentrate and long-term prophylaxis with progestins and tranexamic acid were effective. HAEnCI with a specific mutation in the angiopoietin-1 gene (HAE-ANGPT1) was diagnosed in 4 patients from 1 family and HAEnCI with a specific mutation in the kininogen-1 gene (HAE-KNG1) in 6 patients from 1 family.

Conclusions

A number of clinical differentiators for the different types of HAEnCI have been identified which may support clinicians to narrow down the correct diagnosis of HAEnCI prior to genetic testing and thereby guide appropriate treatment and management decisions. However, confirmation of the causative gene mutation by genetic testing will always be required.
The interplay between EBV and KSHV viral products and NF-κB pathway in oncogenesis
Authors: Charostad J. , Nakhaie M. , Dehghani A. , Faghihloo E.
Published: October 2020

Among the DNA tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV), account for a considerable percentage of virus-associated cancers. Deregulation of transcription factors signaling pathways is one of the most significant oncogenic characteristics of EBV and KSHV. NF-κB is a transcription factor that play a remarkable role in oncogenesis because of its function as a master regulator of a spectrum of genes involved in physiological and pathophysiological process. Constitutive activation of NF-κB is a frequent and well-described event in many human malignancies. Compelling evidence represent EBV and KSHV are capable of targeting different components of NF-κB cascade. Here, we summarized recent findings to clarify the precise relationship between dysregulation of NF-κB and EBV and KSHV-related malignancies. This essay also emphasizes on contribution of various viral products in developing cancer through alteration of NF-κB signaling pathway.
Inhibitory synaptic transmissions to the bed nucleus of the stria terminalis neurons projecting to the ventral tegmental area are enhanced in rats exposed to chronic mild stress
Authors: Hara Ryuto , Takahashi Daiki , Takehara Tatsuhiro , Amano Taiju , Minami Masabumi
Published: October 2020

The comorbidities of depression and chronic pain have long been recognized in the clinic, and several preclinical studies have demonstrated depression-like behaviors in animal models of chronic pain. These findings suggest a common neuronal basis for depression and chronic pain. Recently, we reported that the mesolimbic dopaminergic system was tonically suppressed during chronic pain by enhanced inhibitory synaptic inputs to neurons projecting from the dorsolateral bed nucleus of the stria terminalis (dlBNST) to the ventral tegmental area (VTA), suggesting that tonic suppression of the mesolimbic dopaminergic system by this neuroplastic change may be involved in chronic pain-induced depression-like behaviors. In this study, we hypothesized that inhibitory synaptic inputs to VTA-projecting dlBNST neurons are also enhanced in animal models of depression, thereby suppressing the mesolimbic dopaminergic system. To test this hypothesis, we performed whole-cell patch-clamp electrophysiology using brain slices prepared from rats exposed to chronic mild stress (CMS), a widely used animal model of depression. The results showed a significant enhancement in the frequency of spontaneous inhibitory postsynaptic currents in VTA-projecting dlBNST neurons in the CMS group compared with the no stress group. The findings revealed enhanced inhibitory synaptic inputs to VTA-projecting dlBNST neurons in this rat model of depression, suggesting that this neuroplastic change is a neuronal mechanism common to depression and chronic pain that causes dysfunction of the mesolimbic dopaminergic system, thereby inducing depression-like behaviors.
Short-term fasting accompanying chemotherapy as a supportive therapy in gynecological cancer: protocol for a multicenter randomized controlled clinical trial
Authors: Koppold-Liebscher Daniela , Kessler Christian S. , Steckhan Nico , Bähr Vanessa , Kempter Cornelia , Wischnewsky Manfred , Hübner Marisa , Kunz Barbara , Paul Marion , Zorn Stefanie , Sari Sophia , Jeitler Michael , Stange Rainer , Michalsen Andreas
Published: October 2020

Background/objectives

A few preliminary studies have documented the safety and feasibility of repeated short-term fasting in patients undergoing chemotherapy. However, there is a lack of data from larger randomized trials on the effects of short-term fasting on quality of life, reduction of side effects during chemotherapy, and a possible reduction of tumor progression. Moreover, no data is available on the effectiveness of fasting approaches compared to so-called healthy diets. We aim to investigate whether the potentially beneficial effects of short-term fasting can be confirmed in a larger randomized trial and can compare favorably to a plant-based wholefood diet.

Methods

This is a multicenter, randomized, controlled, two-armed interventional study with a parallel group assignment. One hundred fifty patients, including 120 breast cancer patients and 30 patients with ovarian cancer, are to be randomized to one of two nutritional interventions accompanying chemotherapy: (1) repeated short-term fasting with a maximum energy supply of 350–400 kcal on fasting days or (2) repeated short-term normocaloric plant-based diet with restriction of refined carbohydrates. The primary outcome is disease-related quality of life, as assessed by the functional assessment of the chronic illness therapy measurement system. Secondary outcomes include changes in the Hospital Anxiety and Depression Score and as well as frequency and severity of chemotherapy-induced side effects based on the Common Terminology Criteria of Adverse Events. Explorative analysis in a subpopulation will compare histological complete remissions in patients with neoadjuvant treatments.

Discussion/planned outcomes

Preclinical data and a small number of clinical studies suggest that repeated short-term fasting may reduce the side effects of chemotherapy, enhance quality of life, and eventually slow down tumor progression. Experimental research suggests that the effects of fasting may partly be caused by the restriction of animal protein and refined carbohydrates. This study is the first confirmatory, randomized controlled, clinical study, comparing the effects of short-term fasting to a short-term, plant-based, low-sugar diet during chemotherapy on quality of life and histological tumor remission.

Trial registration

ClinicalTrials.gov NCT03162289. Registered on 22 May 2017
Does a video clip enhance recruitment into a parenting trial? Learnings from a study within a trial
Authors: Mattock Holly C. , Ryan Rachael , O’Farrelly Christine , Babalis Daphne , Ramchandani Paul G.
Published: October 2020

Background

Reaching recruitment targets in randomised controlled trials is a challenge. Media tools are increasingly used to engage participants, yet there is a paucity of research into the use of video to optimise recruitment. We therefore tested whether adding a participant information video clip to a standard participant information sheet improved recruitment into a parenting trial.

Methods

One hundred seven participants were randomised to receive either a participant information sheet (n = 51) or an informational video clip (n = 56) as part of an email contact following a screening phase. All participants went on to receive the information sheet as part of the existing consent procedure.

Results

The video condition did not increase the odds of recruitment into the trial, such that those in the video condition were significantly less likely to participate in the main trial (OR = 0.253, CI = 0.104–0.618, p = 0.003).

Conclusion

The introduction of a video clip into the recruitment stages of a parenting trial did not lead to an improvement in recruitment; however, the small sample size precludes definitive inferences. We offer reflections on challenges encountered in implementing the SWAT and suggestions for other researchers seeking to embed recruitment SWATs into similar trials.

Trial registration

Current controlled trials ISRCTN 58327365. Registered on 19 March 2015.

SWAT registration

SWAT 106; Effects of a video clip on recruitment into a randomised trial. Registered on 20 December 2016.
Systemic profile of immune factors in an elderly Italian population affected by chronic strongyloidiasis
Authors: Tiberti Natalia , Buonfrate Dora , Carbone Carmine , Piro Geny , Bisoffi Zeno , Piubelli Chiara
Published: October 2020

Background

Strongyloidiasis caused by Strongyloides stercoralis is a soil-transmitted helminthiasis affecting an estimated 370 million people and considered one of the most neglected tropical diseases. Although mostly distributed in tropical and subtropical areas, autochthonous infections have also been documented in north-eastern Italy, even though the transmission presumably stopped decades ago. Because of its peculiar auto-infective cycle, strongyloidiasis can persist lifelong, but the pathophysiological mechanisms associated with the maintenance of such a chronic infection are yet to be fully deciphered.

Methods

Serum levels of 23 immune factors were retrospectively assessed in a subgroup of participants in a randomised clinical trial for the treatment of strongyloidiasis (Strong Treat). Here we included Italian subjects born between 1931 and 1964 and diagnosed with strongyloidiasis between 2013 and 2017 (Ss+, n = 32). Serum samples obtained before (BT) and 6 months (6M AT) after ivermectin treatment, as well as from age- and gender-matched uninfected controls (CTRL, n = 34) were analysed.

Results

The assessed immune factors showed a general reduced concertation in Ss+ patients and a lack of association with eosinophilia. In our cohort, we did not observe the classical shift towards a type 2 immune response, since Th1 and Th2 cytokines were mostly unaltered. Instead, we observed chemokines as particularly affected by the presence of the parasite, since IL-8, CCL3, CCL4 and CCL5 were significantly reduced in concentration in Ss+ subjects compared to CTRL, suggesting that immune cell recruitment to the infection site might be dampened in these patients. This observation was further sustained by a significant increase of CCL4, CCL5 and CCL11 concentrations 6M AT. A significant raised systemic concentration of three growth factors, bFGF, PDGF-BB and IL-7 (haematopoietic growth factor) was also observed post-treatment, indicating a potential involvement in restoring tissue integrity and homeostasis following parasite elimination.

Conclusions

These preliminary data suggest that, in order to survive for such a long period, S. stercoralis might suppress host responses that could otherwise result in its ejection. Our results offer novel insights in the potential mechanisms of disease tolerance that might take place during this chronic infection, including a potential T-cell hypo-responsiveness and a role for chemokines.
Associations between Patient Global Assessment scores and pain, physical function, and fatigue in rheumatoid arthritis: a post hoc analysis of data from phase 3 trials of tofacitinib
Authors: Strand Vibeke , Kaine Jeffrey , Alten Rieke , Wallenstein Gene , Diehl Annette , Shi Harry , Germino Rebecca , Murray Christopher W.
Published: October 2020

Background

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We examined the degree to which Patient Global Assessment of Disease Activity (PtGA) was driven by patient-reported assessments of pain (Pain), physical function, and fatigue in patients receiving tofacitinib 5 mg twice daily or placebo, each with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

Methods

This post hoc analysis used data pooled from three randomized controlled trials in csDMARD-inadequate responder (csDMARD-IR) patients (ORAL Scan: NCT00847613; ORAL Standard: NCT00853385; ORAL Sync: NCT00856544). Using subgroup analysis from 2 × 2 tables, associations between PtGA and Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at month 3 were evaluated using Pearson’s Phi correlation coefficients. To support the main analysis, associations between select patient-reported outcomes (PROs) were also evaluated in csDMARD-naïve (ORAL Start; NCT01039688) and biologic (b)DMARD-IR (ORAL Step; NCT00960440) patients.

Results

Across csDMARD-IR treatment groups, low disease activity (defined as PtGA ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in PtGA were associated with mild Pain (Visual Analog Scale score ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in Pain; lack of Pain improvement was associated with little/no improvement in PtGA. In contrast, large proportions of csDMARD-IR patients who reported PtGA improvements did not report HAQ-DI or FACIT-F scores ≥ normative values (≤ 0.25 and ≥ 43.5, respectively) or changes in HAQ-DI or FACIT-F scores ≥ minimum clinically important difference (≥ 0.22 and ≥ 4.0, respectively). Generally, PtGA and Pain outcomes were moderately-to-strongly correlated at month 3 in csDMARD-IR patients, with weaker correlations evident between PtGA and HAQ-DI/FACIT-F outcomes. Similar findings were generally evident in csDMARD-naïve and bDMARD-IR patients.

Conclusions

This analysis supports the role of Pain as a key driver of PtGA in RA; physical function and fatigue play lesser roles in patients’ perceptions of disease activity. These findings corroborate the importance of improved PROs and attainment of low symptom states for optimizing patient care.

Trial registration

Clinicaltrials.gov: NCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009); NCT01039688 (registered: December 25, 2009); NCT00960440 (registered: August 17, 2009)
Lessons learned from a periodontal intervention to reduce progression of chronic kidney disease among Aboriginal Australians
Authors: Jamieson Lisa M. , Sajiv Cherian , Cass Alan , Maple-Brown Louise J. , Skilton Michael R. , Kapellas Kostas , Pawar Basant , Arrow Peter , Askie Lisa M. , Hoy Wendy , Harris David , Brown Alex , Hughes Jaquelyne T.
Published: October 2020

Objective

Periodontal disease is associated with chronic kidney disease (CKD), with both conditions being highly prevalent among Australia’s Aboriginal population. This paper reflects on the lessons learned following implementation of a periodontal intervention in the Central Australian region of the Northern Territory among Aboriginal adults with CKD.

Results

Between Oct 2016 and May 2019, research staff recruited 102 eligible participants. This was far below the anticipated recruitment rate. The challenges faced, and lessons learned, were conceptualised into five specific domains. These included: (1) insufficient engagement with the Aboriginal community and Aboriginal community-controlled organisations; (2) an under-appreciation of the existing and competing patient commitments with respect to general health and wellbeing, and medical treatment to enable all study commitments; (3) most study staff employed from outside the region; (4) potential participants not having the required number of teeth; (5) invasive intervention that involved travel to, and time at, a dental clinic. A more feasible research model, which addresses the divergent needs of participants, communities and service partners is required. This type of approach, with sufficient time and resourcing to ensure ongoing engagement, partnership and collaboration in co-design throughout the conduct of research, challenges current models of competitive, national research funding.
The influences of DNA methylation and epigenetic clocks, on metabolic disease, in middle-aged Koreans
Authors: Lee Ho-Sun , Park Taesung
Published: October 2020

Background

Considering that DNA methylation (DNAm) profiles are, in large part, modifiable by lifestyle and environmental influences, it has been proposed that epigenetic clocks provide a better estimate of biological age than chronological age, as associated with current health status. Even though metabolic diseases induce precocious aging, little is known about associations between metabolic syndrome (MetS) and DNA methylation clocks, and stochastic epigenetic mutations (SEMs), in a Korean population. Therefore, we assessed four different epigenetic clocks (Pan-tissue, Hannum, PhenoAge, and GrimAge), and their accelerations, on MetS and MetS-related lifestyle factors, in Koreans. We measured genome-wide DNA methylation (485,512 CpGs), using an Illumina 450 methylation BeadChip array, with data from 349 blood samples.

Results

DNAm GrimAge strongly correlated with chronological age (r = 0.77, p < 0.001) compared to the other three epigenetic clocks and SEMs. DNAm-based surrogate markers, with regard to MetS, including the gene encoding plasminogen activator inhibitor-1 (PAI1), also correlated with chronological age. Within cohorts stratified by age group, sex, regional area, smoking, and alcohol drinking, a positive correlation was observed between DNAm GrimAge and chronological age (0.43 ≤ r ≤ 0.78). In particular, we identified MetS to associate with accelerated GrimAge, and age-adjusted PAI1, in the middle-age group. Accerelated GrimAge also associated with risk of MetS in the middle-age group (odds ratio = 1.16, p = 0.046), which appears to mediate their associations with fasting glucose. Multiple linear regression showed that DNAm GrimAge, and its acceleration, associate with MetS scores, in the middle-age group (r = 0.26, p = 0.006). Age-adjusted PAI1 was also significantly different between the MetS and control groups, and further associated with MetS scores (r = 0.31, P < 0.001), in the middle age group.

Conclusion

DNAm GrimAge is a surrogate marker for MetS, and its component score, in Koreans. This association can be observed only in middle age. Therefore, appropriate DNA methylation clocks may aid in the prediction of Korean metabolic diseases.
Multiple hepatic aneurysms and dry gangrene of fingertips in eosinophilic granulomatosis with polyangiitis: a case report
Authors: Koh Eunsil , Kang Noeul , Lee Jin-Young , Kim Duk-Kyung , Do Young Soo , Lee Byung-Jae , Choi Dong-Chull
Published: October 2020

Background

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotizing vasculitis mainly affecting small-sized arteries. Involvement of medium-sized vessels is very rare in EGPA. Here we present the case of a patient with EGPA who showed multiple hepatic aneurysms and distal gangrene.

Case presentation

A known EGPA patient visited to the emergency room (ER) with abrupt squeezing abdominal pain. She had suffered from gangrene in the fingertips of both hands for 1 year because of arterial thrombosis associated with hypereosinophilia. However, her absolute eosinophil count in the ER was 1120 cells/µL. An abdomen-pelvis CT demonstrated subcapsular hematoma in the right hepatic lobe. A celiac angiogram demonstrated multiple sized aneurysms in both hepatic lobes and some aneurysms in S7 and S8 were huge, more than 1 cm in size. The shape of the small aneurysms resembled a string of beads, as in polyarteritis nodosa. Given the clinical situation, emergency embolization was performed. Before this patient visited to the ER, she had been treated with a high dose of systemic corticosteroid, azathioprine, and cyclophosphamide. After addition of mepolizumab, the eosinophil count remained stable state with a near zero percentage of total white blood cell count.

Conclusions

Aneurysm and gangrene resulting from the involvement of medium-sized vessels can occur in EGPA. Destruction of vessels might occur even if eosinophil count is below 1500 cells/µL. If involvement of medium-sized arteries is suspected, thorough investigation to identify the involved organs and prompt management are needed to prevent fatal complications.
Imaging features and differential diagnoses of non-neoplastic diffuse mediastinal diseases
Authors: Tabotta Flavian , Ferretti Gilbert R. , Prosch Helmut , Boussouar Samia , Brun Anne-Laure , Roos Justus E. , Ebner Lukas , Letovanec Igor , Brauner Michel , Beigelman-Aubry Catherine
Published: October 2020

Acute or chronic non-neoplastic diffuse mediastinal diseases have multiple causes, degrees of severity, and a wide range of management. Some situations require emergency care while others do not need specific treatment. Although the diagnosis may be suspected on chest X-ray, it is mainly based on CT. A delayed recognition is not uncommonly observed. Some findings may prompt the radiologist to look for specific associated injuries or lesions.

This pictorial review will successively describe the various non-neoplastic causes of diffuse mediastinal diseases with their typical findings and major differentials.

First, pneumomediastinum that can be provoked by extra- or intra-thoracic triggers requires the knowledge of patient’s history or recent occurrences. Absence of any usual etiological factor should raise suspicion of cocaine inhalation in young individuals.

Next, acute mediastinitis may be related to post-operative complications, esophageal perforation, or contiguous spread of odontogenic or retropharyngeal infections. The former diagnosis is not an easy task in the early stage, owing to the similarities of imaging findings with those of normal post-operative appearance during the first 2–3 weeks.

Finally, fibrosing mediastinitis that is linked to an excessive fibrotic reaction in the mediastinum with variable compromise of mediastinal structures, in particular vascular and airway ones. Differential diagnosis includes tumoral and inflammatory infiltrations of the mediastinum.
Role of imaging in visceral vascular emergencies
Authors: Karaosmanoglu Ali Devrim , Uysal Aycan , Akata Deniz , Ozmen Mustafa Nasuh , Karcaaltincaba Musturay
Published: October 2020

Differential diagnosis in non-traumatic acute abdomen is broad and unrelated diseases may simulate each other from a clinical perspective. Despite the fact that they are not as common, acute abdominal pain due to diseases related to visceral vessels may be life-threating if not detected and treated promptly. Thrombosis, dissection, and aneurysm in the abdominal visceral arteries or thrombosis in visceral veins may cause acute abdominal pain. Imaging with appropriate protocoling plays a fundamental role in both early diagnosis and determination of the treatment approach in these cases where early treatment can be life-saving. Computed tomography (CT) appears to be the most effective modality for the diagnosis as it provides high detail images in a very short time. Patient cooperation is also a less concern as compared to magnetic resonance imaging (MRI). As the imaging findings may sometimes be really subtle, diagnosis may be difficult especially to inexperienced imagers. Correct protocoling is also very critical to detect arterial abnormalities as visceral arterial abnormalities may not be detectable in portal phase only abdominal CT scans. In this article, we aimed to increase awareness among imaging specialists to these not very common causes of acute abdomen.
Application of human amniotic epithelial cells in regenerative medicine: a systematic review
Authors: Zhang Qiuwan , Lai Dongmei
Published: October 2020

Human amniotic epithelial cells (hAECs) derived from placental tissues have gained considerable attention in the field of regenerative medicine. hAECs possess embryonic stem cell-like proliferation and differentiation capabilities, and adult stem cell-like immunomodulatory properties. Compared with other types of stem cell, hAECs have special advantages, including easy isolation, plentiful numbers, the obviation of ethical debates, and non-immunogenic and non-tumorigenic properties. During the past two decades, the therapeutic potential of hAECs for treatment of various diseases has been extensively investigated. Accumulating evidence has demonstrated that hAEC transplantation helps to repair and rebuild the function of damaged tissues and organs by different molecular mechanisms. This systematic review focused on summarizing the biological characteristics of hAECs, therapeutic applications, and recent advances in treating various tissue injuries and disorders. Relevant studies published in English from 2000 to 2020 describing the role of hAECs in diseases and phenotypes were comprehensively sought out using PubMed, MEDLINE, and Google Scholar. According to the research content, we described the major hAEC characteristics, including induced differentiation plasticity, homing and differentiation, paracrine function, and immunomodulatory properties. We also summarized the current status of clinical research and discussed the prospects of hAEC-based transplantation therapies. In this review, we provide a comprehensive understanding of the therapeutic potential of hAECs, including their use for cell replacement therapy as well as secreted cytokine and exosome biotherapy. Moreover, we showed that the powerful immune-regulatory function of hAECs reveals even more possibilities for their application in the treatment of immune-related diseases. In the future, establishing the optimal culture procedure, achieving precise and accurate treatment, and enhancing the therapeutic potential by utilizing appropriate preconditioning and/or biomaterials would be new challenges for further investigation.