bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute epiglottitis
Authors: El Hitti Dr Eric
Published: July 2020

Epiglottitis is the inflammation of the epiglottis and adjacent supraglottic structures. Early recognition of specific symptoms, as well as the systemic signs of sepsis, can help prevent serious complications. A good understanding of the steps in the management of the condition aids early intervention and treatment. The priority of treatment is to secure the airway. Serious complications can occur in addition to the severity of the disease. Symptoms can be more prolonged depending on the aetiology. If the epiglottis is still swollen after 72 hours of treatment, then further investigation should be carried out.
Physical exercise training in patients with a Fontan circulation: A systematic review
Authors: Scheffers Linda E , Berg Linda E M vd , Ismailova Gamida , Dulfer Karolijn , Takkenberg Johanna J M , Helbing Wim A
Published: July 2020

Background

Patients with a Fontan circulation have a reduced exercise capacity, which is an important prognostic predictor of morbidity and mortality. A way to increase exercise capacity in Fontan patients might be exercise training. This systematic review assesses the effects of exercise training investigated in Fontan patients in order to provide an overview of current insights.

Design and methods

Studies evaluating an exercise training intervention in Fontan patients published up to February 2020 were included in this systematic review.

Results

From 3000 potential studies, 16 studies reported in 22 publications met the inclusion criteria. In total, 264 Fontan patients with mean age range 8.7–31 years, were included. Different training types including inspiratory muscle training, resistance training and aerobic training were investigated. Main outcome measures reported were peak oxygen uptake, cardiac function, lung function, physical activity levels and quality of life. Peak oxygen uptake increased significantly in 56% of the studies after training with an overall mean increase of +1.72 ml/kg/min (+6.3%). None of the studies reported negative outcome measures related to the exercise programme. In four studies an adverse event was reported, most likely unrelated to the training intervention.

Conclusions

Exercise training in Fontan patients is most likely safe and has positive effects on exercise capacity, cardiac function and quality of life. Therefore exercise training in Fontan patients should be encouraged. Further studies are required to assess the optimal training type, intensity, duration and long-term effects.
Use of colour Doppler to eliminate rectal bleeding from trans-rectal ultrasound-guided biopsy of the prostate
Authors: Aminu Sani R , Ansari Asif H , Rana Muhammad Q
Published: July 2020

Bleeding is one of the complications of trans-rectal ultrasound (TRUS)-guided biopsy of the prostate. Urethral bleeding could be prevented by avoiding the trajectory on the urethra. However, rectal bleeding is difficult to predict because the peri-prostatic, intra-prostatic and rectal vessels cannot be seen on an ordinary ultrasound scan. Use of colour Doppler to map out the vessels cognitively before injection of local anaesthesia prevents puncture of the vessels, which is a key cause of rectal bleeding.

Level of evidence:

Not applicable.
Henoch–Schönlein purpura and epididymitis in an adult: A case report and literature review
Authors: McAdam Andrew , Thompson Trevor
Published: July 2020

Henoch–Schönlein purpura (HSP) is a small-vessel immunoglobulin A1-mediated vasculitis which often presents as a purpuric rash affecting the cutaneous tissue, gastrointestinal tract and joints. Commonly reported in childhood is scrotal involvement with pain and swelling, but this is exceptionally rare in the adult population. We report a case of a 33-year-old male with bilateral testicular pain and swelling on the background of concurrent HSP. The history, examination, subsequent investigations and ultrasound scan confirmed a non-bacterial and non-viral epididymo-orchitis. This was managed effectively with systemic steroids and topical emollients for symptomatic relief. This is a rare but important manifestation of HSP for clinicians assessing HSP patients with acute testicular pain.

Level of evidence

Level 5.
“Smittestopp”: If you want your freedom back, download now
Authors: Sandvik Kristin B
Published: July 2020

The intervention attempts to engage critically with the Smittestopp app as a specifically Norwegian technofix. Culturally and politically, much of the Covid-19 response and the success of social distancing rules have been organized around the widespread trust in the government and public health authorities, and a focus on the citizens’ duty to contribute to the dugnaðr. The intervention argues that Smittestopp has been co-created by the mobilization of trust and dugnaðr, resulting in the launch of an incomplete and poorly defined data-hoarding product with significant vulnerabilities.
How partners of pregnant women use their social networks when preparing for childbirth and parenthood: A qualitative study
Authors: Bäckström Caroline , Larsson Therese , Thorstensson Stina
Published: July 2020

Social contextual circumstances have an influence on parental transition, and social support has been shown to facilitate the transition to parenthood, among other states. Further knowledge is, however, needed to explore how partners of pregnant women use their social networks during pregnancy. Therefore, the aim of this study was to explore how partners of pregnant women use their social networks when preparing for childbirth and parenting. Within this study, a social network is defined as social connections such as family, friends and significant others. In total, 14 partners (expectant fathers and co-mothers) were interviewed. Data were analysed using qualitative content analysis. EQUATOR Network guidelines and the COREQ checklist were applied. The analysis resulted in one theme of meaning: Partners use their social networks to receive social support, which facilitates understanding about how to prepare for childbirth and parenthood, which was described through three sub-themes. The results highlight the importance of social networks for partners when preparing for childbirth and parenthood. Professionals should aim to strengthen and extend partners’ social networks and access to social support. This could be done not only to support partners to attend parental classes, but also to participate socially as well as engage with other expectant parents within the classes.
Self-Efficacy and Subjective Norms as Moderators in the Networking Competence–Social Entrepreneurial Intentions Link
Authors: Igwe Anthony , Ogbo Anastasia , Agbaeze Emmanuel , Abugu James , Ezenwakwelu Charity , Okwo Henry
Published: July 2020

This study examines self-efficacy and subjective norms (moral obligation, empathy, and perceived social support) as moderators of the effect networking competence has on social entrepreneurial intentions. Using Nigeria as a study area, a survey was conducted on 541 budding entrepreneurs, which were students with a high entrepreneurial propensity. With the use of Andrew Hayes’s PROCESS macro, a simultaneous regression analysis was performed to establish the interaction effect of the selected moderators. The results show a positive main effect of networking competence on social entrepreneurial intentions, statistically significant interaction effects of empathy and perceived social support, no interaction effect of moral obligation, and a poor self-efficacy fit. This study extends theories of entrepreneurial intentions and the mediation (additive) models of Mair & Noboa, Krueger, and Hockerts. Suggestions are that other studies should be carried out using self-efficacy among actual early-level entrepreneurs, with a likelihood that results could explain what role self-efficacy could have in predicting social entrepreneurial intentions.
Do Women Directors Impact the Risk and Return of Indian Banks?
Authors: Shukla Ankur , Sivasankaran Narayanasamy , Singh Prakash , Kanagaraj Ayyaluswamy , Chakraborty Shibashish
Published: July 2020

The purpose of the paper is to investigate whether women directors impact the risk and return of Indian banks. This study employs panel data models for a sample of 29 Indian banks that form part of the National Stock Exchange 500 index for the period 2009–2016. This paper concludes that women directors influence the accounting returns (measured through Return on Assets) of Indian banks. However, it was found that women directors did not affect the risks (measured through Equity Beta and gross NPA to Total Assets) of the sample banks. This paper contributes to the literature and practitioners in several ways. To the best of the knowledge of the authors, no study has examined the impact of women directors on the risk and return of banks operating in India. Hence, the findings of this article have substantial implications both to academia and practitioners.
Stacked genetically modified soybean harboring herbicide resistance and insecticide rCry1Ac shows strong defense and redox homeostasis disturbance after glyphosate-based herbicide application
Authors: Zanatta Caroline Bedin , Benevenuto Rafael Fonseca , Nodari Rubens Onofre , Agapito-Tenfen Sarah Zanon
Published: July 2020

Background

World agricultural production of genetically modified (GM) products, in particular, the combination of different traits/genes in the same plant has been a trend over the last decade. There have been concerns raised over stacking multiple herbicide and insect-resistant transgenes that could result in fitness costs depending on the type and strength of selection pressures exerted by the environment. Here, we report the results of transcriptomic analysis comparing the effect of glyphosate-based herbicide (GBH) in the single-transgene versus stacked, herbicide-resistant soybean varieties on various biological processes, metabolic pathways, and key shikimic enzymes.

Results

Gene expression data showed that defense metabolism and redox homeostasis were equally modulated in single-transgene and stacked-variety samples. Carbon accumulation and energy metabolisms were distinct between the varieties and photosynthesis metabolism was found negatively affected in the single-transgene variety only. In the stacked variety, the shikimate pathway was modulated by the accumulation of transcripts from phenylalanine gene and other cascade genes. As expected, the expression of native EPSPS was upregulated in both varieties when herbicide was applied. On the other hand, transgenic EPSPS expression was down-regulated in both GM varieties upon herbicide application which cannot be explained.

Conclusion

Glyphosate-based herbicides toxicity suggests its effects on carbon central metabolism and flux, redox metabolism, photosynthesis, and to hormone and defense response in plants. The observed unintended effects in GM herbicide-tolerant varieties unravel the deleterious effects previously observed on GM-tolerant varieties growth and production. The impact of GBH on shikimate and cascade pathways was observed in terms of both native and transgenic insensitive EPSPS modulation, alteration of jasmonic acid and lignin metabolism in both single-transgene and stacked variety. The energy metabolism and carbon flux were differently affected in these varieties. Oxidative stress, more specifically glutathione metabolism, induced by GBH, was also observed in this study. The stacked variety showed a more pronounced stress response (activation of specific stress defense proteins, Rboh, WRKY) and secondary compounds (β-glucosidase, isoflavone 7-O-methyltransferase). Omics profiling techniques, such as transcriptomics, can be considered tools to support risk assessment in detecting unintended effects due to the GBH application.
Correction to: Sudden onset of syncope and disseminated intravascular coagulation at 14 weeks of pregnancy: a case report
Authors: Kamata Mayumi , Maruyama Tetsuo , Nishiguchi Tomizo , Iwasaki Shinya
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
Cost-effectiveness of inhaled oxytocin for prevention of postpartum haemorrhage: a modelling study applied to two high burden settings
Authors: Carvalho Natalie , Hoque Mohammad Enamul , Oliver Victoria L. , Byrne Abbey , Kermode Michelle , Lambert Pete , McIntosh Michelle P. , Morgan Alison
Published: July 2020

Background

Access to oxytocin for prevention of postpartum haemorrhage (PPH) in resource-poor settings is limited by the requirement for a consistent cold chain and for a skilled attendant to administer the injection. To overcome these barriers, heat-stable, non-injectable formulations of oxytocin are under development, including oxytocin for inhalation. This study modelled the cost-effectiveness of an inhaled oxytocin product (IHO) in Bangladesh and Ethiopia.

Methods

A decision analytic model was developed to assess the cost-effectiveness of IHO for the prevention of PPH compared to the standard of care in Bangladesh and Ethiopia. In Bangladesh, introduction of IHO was modelled in all public facilities and home deliveries with or without a skilled attendant. In Ethiopia, IHO was modelled in all public facilities and home deliveries with health extension workers. Costs (costs of introduction, PPH prevention and PPH treatment) and effects (PPH cases averted, deaths averted) were modelled over a 12-month program. Life years gained were modelled over a lifetime horizon (discounted at 3%). Cost of maintaining the cold chain or effects of compromised oxytocin quality (in the absence of a cold chain) were not modelled.

Results

In Bangladesh, IHO was estimated to avert 18,644 cases of PPH, 76 maternal deaths and 1954 maternal life years lost. This also yielded a cost-saving, with the majority of gains occurring among home deliveries where IHO would replace misoprostol. In Ethiopia, IHO averted 3111 PPH cases, 30 maternal deaths and 767 maternal life years lost. The full IHO introduction program bears an incremental cost-effectiveness ratio (ICER) of between 2 and 3 times the per-capita Gross Domestic Product (GDP) ($1880 USD per maternal life year lost) and thus is unlikely to be considered cost-effective in Ethiopia. However, the ICER of routine IHO administration considering recurring cost alone falls under 25% of per-capita GDP ($175 USD per maternal life-year saved).

Conclusions

IHO has the potential to expand access to uterotonics and reduce PPH-associated morbidity and mortality in high burden settings. This can facilitate reduced spending on PPH management, making the product highly cost-effective in settings where coverage of institutional delivery is lagging.
Bacillus subtilis spore vaccines displaying protective antigen induce functional antibodies and protective potency
Authors: Oh Yeonsu , Kim Jung Ae , Kim Chang-Hwan , Choi Soo-Keun , Pan Jae-Gu
Published: July 2020

Background

Bacillus anthracisis the causative agent of anthrax, a disease of both humans and various animal species, and can be used as a bioterror agent. Effective vaccines are available, but those could benefit from improvements, including increasing the immunity duration, reducing the shot frequency and adverse reactions. In addition, more sophisticated antigen delivery and potentiation systems are urgently required.

The protective antigen (PA), one of three major virulence factors associated with anthrax was displayed on the surface ofBacillus subtilisspores, which is a vaccine production host and delivery vector with several advantages such as a low production cost, straightforward administration as it is safe for human consumption and the particulate adjuvanticity. Mice were immunized orally (PO), intranasally (IN), sublingually (SL) or intraperitoneally (IP) with the PA displaying probiotic spore vaccine. Clinical observation, serological analysis and challenge experiment were conducted to investigate the safety and efficacy of the vaccine.

Results

A/J mice immunized with the PA spore vaccine via PO, IN, SL, and IP were observed to have increased levels of active antibody titer, isotype profiles and toxin neutralizing antibody in sera, and IgA in saliva. The immunized mice were demonstrated to raise protective immunity against the challenge with lethalB. anthracisspores.

Conclusions

In this study, we developed aB. subtilisspore vaccine that displays the PA on its surface and showed that the PA-displaying spore vaccine was able to confer active immunity to a murine model based on the results of antibody isotype titration, mucosal antibody identification, and a lethal challenge experiment.
The pathophysiology of ‘happy’ hypoxemia in COVID-19
Authors: Dhont Sebastiaan , Derom Eric , Van Braeckel Eva , Depuydt Pieter , Lambrecht Bart N.
Published: July 2020

The novel coronavirus disease 2019 (COVID-19) pandemic is a global crisis, challenging healthcare systems worldwide. Many patients present with a remarkable disconnect in rest between profound hypoxemia yet without proportional signs of respiratory distress (i.e. happy hypoxemia) and rapid deterioration can occur. This particular clinical presentation in COVID-19 patients contrasts with the experience of physicians usually treating critically ill patients in respiratory failure and ensuring timely referral to the intensive care unit can, therefore, be challenging. A thorough understanding of the pathophysiological determinants of respiratory drive and hypoxemia may promote a more complete comprehension of a patient’s clinical presentation and management. Preserved oxygen saturation despite low partial pressure of oxygen in arterial blood samples occur, due to leftward shift of the oxyhemoglobin dissociation curve induced by hypoxemia-driven hyperventilation as well as possible direct viral interactions with hemoglobin. Ventilation-perfusion mismatch, ranging from shunts to alveolar dead space ventilation, is the central hallmark and offers various therapeutic targets.
Sexual dimorphism of gut microbiota at different pubertal status
Authors: Yuan Xin , Chen Ruimin , Zhang Ying , Lin Xiangquan , Yang Xiaohong
Published: July 2020

Background

Accumulating evidence infer that gut microbiome-host relations are key mediators or modulators driving the observed sexual dimorphism in some disease onset and progression. To date, the sex-differences of gut microbiota at different pubertal status have not been reported.

Objective

To determine the characteristics of gut microbiota of both genders at different pubertal status.

Methods

Gut microbiota was analyzed in 89 Chinese participants aged 5–15 years. Participants were divided into pre-puberty and puberty groups for both male and female. The composition of gut microbiota was investigated by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed. The prediction of metagenomic functional content from 16S rRNA gene surveys was conducted.

Results

There were 49 males (9.76 ± 2.15 years) and 40 females (9.74 ± 1.63 years); 21 males and 26 females were at puberty. At genus level, Alistipes, Megamonas, Oscillospira and Parabacteroides were more prevalent in girls than in boys (p < 0.05). There were no significantly differences of alpha-diversity between genders, which was independent of pubertal status. The beta-diversity was significantly different in pubertal subjects between genders. Using statistical analyses, we assigned genera Dorea, Megamonas, Bilophila, Parabacteroides and Phascolarctobacterium as microbial markers for pubertal subjects. The predicted metabolic profiles differ in both pubertal and pre-pubertal groups between genders.

Conclusion

This cross-sectional study revealed that sex differences in the gut microbiota composition and predicted metabolic profiles exist before puberty, which become more significant at puberty. The identification of novel puberty bacterial markers may disclose a potential effects of gender-related microbiota profiles on puberty onset.
Inhibition of Delta-like Ligand 4 enhances the radiosensitivity and inhibits migration in cervical cancer via the reversion of epithelial–mesenchymal transition
Authors: Yang Shan-Shan , Yu De-Yang , Du Yu-Ting , Wang Le , Gu Lina , Zhang Yun-Yan , Xiao Min
Published: July 2020

Background

Concurrent chemoradiotherapy is the common first-line treatment for patients with advanced cervical cancer. However, radioresistance remains a major clinical challenge, which results in recurrence and poor survival. Many studies have shown the potential of Delta-like Ligand 4 (DLL4) as a novel prognostic biomarker and therapeutic target in many solid tumors. Previously, we have found that high DLL4 expression in tumor cells may predict the pelvic lymph node metastasis and poor prognosis in patients with cervical cancer. In our present study, we further studied the effects of DLL4 on the biological behavior and radiosensitivity of cervical cancer cells.

Methods

The expression of DLL4 and epithelial–mesenchymal transition (EMT) phenotype markers in cervical cancer cell lines or tissues were detected using Western blotting, and the expression of DLL4 mRNA in cervical cancer cell lines or tissues was detected using Quantitative real-time PCR. The effect of DLL4 on cell proliferation, migration, and radiosensitivity was evaluated using the CCK8 assay, flow cytometry, Transwell assays for cell invasion and migration, and Immunofluorescence staining in vitro.

Results

The expression of DLL4 in radiotherapy-resistant SiHa cells was significantly higher than that in radiotherapy-sensitive Me-180 cells. Furthermore, downregulation of DLL4 enhanced the radiosensitivity of SiHa and Caski cells via the inhibition of cell proliferation, promotion of radiation-induced apoptosis, and inhibition of the DNA damage repair. Moreover, downregulation of DLL4 inhibited the EMT and reduced the proliferation, invasion, and migration ability in SiHa and Caski cells. Consistent with the DLL4 expression in the cell lines, the expression of DLL4 in the tissues of the radioresistant group was also higher than that of the radiosensitive group.

Conclusions

Downregulation of DLL4 inhibited the progression and increased the radiosensitivity in cervical cancer cells by reversing EMT. These results indicated the promising prospect of DLL4 against the radioresistance and metastasis of cervical cancer and its potential as a predictive biomarker for radiosensitivity and prognosis in patients with cervical cancer patients receiving concurrent chemoradiotherapy (cCRT).
The International Health Regulations (2005), the threat of populism and the COVID-19 pandemic
Authors: Wilson Kumanan , Halabi Sam , Gostin Lawrence O.
Published: July 2020

The global response to the COVID-19 pandemic has laid bare weaknesses and major challenges in the international approach to managing public health emergencies. Populist sentiment is spreading globally as democratic nations are increasing their support for or electing governments that are perceived to represent “traditional” native interests. Measures need to be taken to proactively address populist sentiment when reviewing the IHR (2005) effectiveness in the COVID-19 pandemic. We discuss how populism can impact the IHR (2005) and conversely how the IHR (2005) may be able to address populist concerns if the global community commits to helping states address public health threats that emerge within their borders.
Bibliometric analysis of scientific publications on “sustainable development goals” with emphasis on “good health and well-being” goal (2015–2019)
Authors: Sweileh Waleed M.
Published: July 2020

Background

Global progress in the United Nations’ Sustainable Development Goals (SDGs) requires significant national and international research efforts and collaboration. The current study aimed to provide policymakers, academics, and researchers with a snapshot of global SDGs-related research activity.

Method

This was a cross-sectional descriptive bibliometric study. SciVerse Scopus was used to retrieve SDGs-related research publications for the period from 2015 to 2019.

Results

In total, 18,696 documents were found. The Sustainability journal ranked first (n = 1008; 5.4%) in the number of SDGs-related publications. The World Health Organization was the most active institution in publishing SDGs-related documents (n = 581; 1.3%). Most of the retrieved documents belonged to SDG 17 (partnership) followed by SDG 13 (climate action), and SDG 12 (responsible consumption and production), while SDG 7 (affordable and clean energy) had the least number of publications. The European region (n = 9756; 52.2%) had the highest research contribution while the Eastern Mediterranean region (n = 1052; 5.6%) had the least contribution. After exclusion of SDG 17, the SDG 3 (good health and well-being) was the top researched SDG for the African region, the Eastern Mediterranean regions, and the South-Eastern Asian region. For the region of the Americas, European region, and the Western Pacific region, the SDG 13 (climate action) was the most researched. The SDG 7 (affordable and clean energy) was the least researched in the African region, the region of the Americas, the European region, and the South-East Asian region. In the Eastern Mediterranean region, SDG 10 (reduced inequality) was the least researched while in the Western Pacific region, SDG 5 (gender inequality) was the least researched. The most researched targets of SDG 3 were targets 7 (sexual and reproductive health services) and 8 (universal health coverage) while the least researched targets were 5 (substance use disorders) and 9 (death from hazardous materials). International research collaboration within SDG 3 between high- and low-income countries was inadequate.

Conclusion

The analysis presented in the current study are useful for researchers, institutes, governments, funding agencies, and policy-makers. Countries in Africa, the Middle East, and South-East Asia need to increase their funding and research collaboration in the field of SDGs.
Humanism in clinical education: a mixed methods study on the experiences of clinical instructors in Iran
Authors: Hazrati Hakimeh , Bigdeli Shoaleh , Gavgani Vahideh Zarea , Soltani Arabshahi Seyed Kamran , Behshid Mozhgan , Sohrabi Zohreh
Published: July 2020

Background

Medical education is currently more considerate about the human dimension. The present qualitative study aimed to explain the experiences of clinical professors with regard to humanism in clinical education in Iran.

Methods

This mixed methods study had two phases, a quanitative phase of scientometrics and a qualitative phase of a content analysis. In the scientometrics phase, Ravar PreMap and VOSviewer software programs were utilized for plotting the conceptual networks. The networks were analyzed at the micro-level based on centrality indices (closeness, degree, and betweenness). The conceptual network was plotted and the prominent topics in clinical education were identified using co-word analysis. In the second qualitative phase on the topic, based on the scientometrics phase, semi-structured interviews were conducted with clinical professors. The interviews were transcribed verbatim and analyzed.

Results

On the basis of the analysis of titles, abstracts, and keywords of the retrieved articles on clinical education from ISI Web of Science, Scopus, and PubMed, 1412 keywords were extracted. After the refining process, 356 keywords with 6741 relations remained. Upon plotting the conceptual network, 19 conceptual clusters related to clinical education were obtained. Then, micro-level network analysis (centrality criteria) indicated that the keyword humanism with the frequency of 137 had the highest rate (97.753), closeness (97.802), and betweenness (13.407). Moreover, from the interview data analysis, two themes of “intertwined nature of the human spirit in clinical education” and “humanistic behavior of professors in clinical education” were extracted.

Conclusion

As a part of the educational culture, humanistic values must be intertwined with the medical education curriculum. In this regard, humanism and clinical reasoning are the two major clusters of clinical teaching; moreover, altruism and adherence to humanistic values, and scientific qualification are other main pillars that should be considered as the criteria for the selection of clinical professors and medical students.
Recurrence of spontaneous pneumothorax six years after VATS pleurectomy: evidence for formation of neopleura
Authors: Germonpre Peter , Van Renterghem Elke , Dechamps Nicolas , Onghena Thierry , Van Aken Joke
Published: July 2020

Background

Primary Spontaneous Pneumothorax (PSP) is considered an absolute and definitive contraindication for scuba diving and professional flying, unless bilateral surgical pleurectomy is performed. Only then is there a sufficiently low risk of recurrence to allow a waiver for flying and/or diving.

Case presentation

A young fit male patient who suffered a PSP 6 years ago, and underwent an uncomplicated videoscopic surgical pleurectomy, presented with a complete collapse of the lung on the initial PSP side. Microscopic examination of biopsies showed a slightly inflamed tissue but otherwise normal mesothelial cells, compatible with newly formed pleura.

Conclusions

Even with pleurectomy, in this patient, residual mesothelial cells seem to have had the capacity to create a completely new pleura and pleural space. The most appropriate surgical technique for prevention of PSP may still be debated.
EZH2: a novel target for cancer treatment
Authors: Duan Ran , Du Wenfang , Guo Weijian
Published: July 2020

Enhancer of zeste homolog 2 (EZH2) is enzymatic catalytic subunit of polycomb repressive complex 2 (PRC2) that can alter downstream target genes expression by trimethylation of Lys-27 in histone 3 (H3K27me3). EZH2 could also regulate gene expression in ways besides H3K27me3. Functions of EZH2 in cells proliferation, apoptosis, and senescence have been identified. Its important roles in the pathophysiology of cancer are now widely concerned. Therefore, targeting EZH2 for cancer therapy is a hot research topic now and different types of EZH2 inhibitors have been developed. In this review, we summarize the structure and action modes of EZH2, focusing on up-to-date findings regarding the role of EZH2 in cancer initiation, progression, metastasis, metabolism, drug resistance, and immunity regulation. Furtherly, we highlight the advance of targeting EZH2 therapies in experiments and clinical studies.
SBRT combined with PD-1/PD-L1 inhibitors in NSCLC treatment: a focus on the mechanisms, advances, and future challenges
Authors: Chen Yu , Gao Min , Huang Zhaoqin , Yu Jinming , Meng Xiangjiao
Published: July 2020

Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1), programmed cell death ligand-1 (PD-L1), and others have shown potent clinical efficacy and have revolutionized the treatment protocols of a broad spectrum of tumor types, especially non–small-cell lung cancer (NSCLC). Despite the substantial optimism of treatment with PD-1/PD-L1 inhibitors, there is still a large proportion of patients with advanced NSCLC who are resistant to the inhibitors. Preclinical and clinical trials have demonstrated that radiotherapy can induce a systemic antitumor immune response and have a great potential to sensitize refractory “cold” tumors to immunotherapy. Stereotactic body radiation therapy (SBRT), as a novel radiotherapy modality that delivers higher doses to smaller target lesions, has shown favorable antitumor effects with significantly improved local and distant control as well as better survival benefits in various solid tumors. Notably, research has revealed that SBRT is superior to conventional radiotherapy, possibly because of its more powerful immune activation effects. Thus, PD-1/PD-L1 inhibitors combined with SBRT instead of conventional radiotherapy might be more promising to fight against NSCLC, further achieving more favorable survival outcomes. In this review, we focus on the underlying mechanisms and recent advances of SBRT combined with PD-1/PD-L1 inhibitors with an emphasis on some future challenges and directions that warrant further investigation.
Computer tomographic assessment of gastric volume in major trauma patients: impact of pre-hospital airway management on gastric air
Authors: Mitteregger Thomas , Schwaiger Philipp , Kreutziger Janett , Schöchl Herbert , Oberladstätter Daniel , Trimmel Helmut , Voelckel Wolfgang G.
Published: July 2020

Background

Gastric dilation is frequently observed in trauma patients. However, little is known about average gastric volumes comprising food, fluids and air. Although literature suggests a relevant risk of gastric insufflation when endotracheal intubation (ETI) is required in the pre-hospital setting, this assumption is still unproven.

Methods

Primary whole body computed tomographic (CT) studies of 315 major trauma patients admitted to our Level 1 Trauma Centre Salzburg during a 7-year period were retrospectively assessed. Gastric volumes were calculated employing a CT volume rendering software. Patients intubated in the pre-hospital setting by emergency physicians (PHI, N = 245) were compared with spontaneously breathing patients requiring ETI immediately after arrival in the emergency room (ERI, N = 70).

Results

The median (range) total gastric content and air volume was 402 (26–2401) and 94 (0–1902) mL in PHI vs. 466 (59–1915) and 120 (1–997) mL in ERI patients (p = .59 and p = .35). PHI patients were more severely injured when compared with the ERI group (injury severity score (ISS) 33 (9–75) vs. 25 (9–75); p = .004). Mortality was higher in the PHI vs. ERI group (26.8% vs. 8.6%, p = .001). When PHI and ERI patients were matched for sex, age, body mass index and ISS (N = 50 per group), total gastric content and air volume was 496 (59–1915) and 119 (0–997) mL in the PHI vs. 429 (36–1726) and 121 (4–1191) mL in the ERI group (p = .85 and p = .98). Radiologic findings indicative for aspiration were observed in 8.1% of PHI vs. 4.3% of ERI patients (p = .31). Gastric air volume in patients who showed signs of aspiration was 194 (0–1355) mL vs. 98 (1–1902) mL in those without pulmonary CT findings (p = .08).

Conclusion

In major trauma patients, overall stomach volume deriving from food, fluids and air must be expected to be around 400–500 mL. Gastric dilation caused by air is common but not typically associated with pre-hospital airway management. The amount of air in the stomach seems to be associated with the risk of aspiration. Further studies, specifically addressing patients after difficult airway management situations are warranted.
12q14.3 microdeletion involving HMGA2 gene cause a Silver-Russell syndrome-like phenotype: a case report and review of the literature
Authors: Mercadante Francesca , Busè Martina , Salzano Emanuela , Fragapane Tiziana , Palazzo Daniela , Malacarne Michela , Piccione Maria
Published: July 2020

Background

Silver-Russell Syndrome (SRS) is a genetic disorder characterized by intrauterine and postnatal growth restriction and normal head circumference with consequent relative macrocephaly. Addictional findings are protruding forehead in early life, body asymmetry (of upper and lower limbs) and substantial feeding difficulties. Although several genetic mechanisms that cause the syndrome are known, more than 40% of patients with a SRS-like phenotype remain without an etiological diagnosis. In the last few years, different clinical reports have suggested that mutations or deletions of the HMGA2 gene can be responsible for a SRS-like phenotype in patients with negative results of the common diagnostic tests for this syndrome.

Case presentation

We present a 3-year-old male patient with clinical diagnosis of Silver-Russell Syndrome (SRS) associated with a de novo heterozygous deletion of the long arm of the chromosome 12 (12q14.3) encompassing the HMGA2 gene.

Conclusions

Our report confirms the etiological role of HMGA2 as a disease gene in the development of a SRS-like phenotype.
Airway pressure morphology and respiratory muscle activity during end-inspiratory occlusions in pressure support ventilation
Authors: Soundoulounaki Stella , Akoumianaki Evangelia , Kondili Eumorfia , Pediaditis Emmanouil , Prinianakis Georgios , Vaporidi Katerina , Georgopoulos Dimitris
Published: July 2020

Background

The driving pressure of the respiratory system is a valuable indicator of global lung stress during passive mechanical ventilation. Monitoring lung stress in assisted ventilation is indispensable, but achieving passive conditions in spontaneously breathing patients to measure driving pressure is challenging. The accuracy of the morphology of airway pressure (Paw) during end-inspiratory occlusion to assure passive conditions during pressure support ventilation has not been examined.

Methods

Retrospective analysis of end-inspiratory occlusions obtained from critically ill patients during pressure support ventilation. Flow, airway, esophageal, gastric, and transdiaphragmatic pressures were analyzed. The rise of gastric pressure during occlusion with a constant/decreasing transdiaphragmatic pressure was used to identify and quantify the expiratory muscle activity. The Paw during occlusion was classified in three patterns, based on the differences at three pre-defined points after occlusion (0.3, 1, and 2 s): a “passive-like” decrease followed by plateau, a pattern with “clear plateau,” and an “irregular rise” pattern, which included all cases of late or continuous increase, with or without plateau.

Results

Data from 40 patients and 227 occlusions were analyzed. Expiratory muscle activity during occlusion was identified in 79% of occlusions, and at all levels of assist. After classifying occlusions according to Paw pattern, expiratory muscle activity was identified in 52%, 67%, and 100% of cases of Paw of passive-like, clear plateau, or irregular rise pattern, respectively. The driving pressure was evaluated in the 133 occlusions having a passive-like or clear plateau pattern in Paw. An increase in gastric pressure was present in 46%, 62%, and 64% of cases at 0.3, 1, and 2 s, respectively, and it was greater than 2 cmH2O, in 10%, 20%, and 15% of cases at 0.3, 1, and 2 s, respectively.

Conclusions

The pattern of Paw during an end-inspiratory occlusion in pressure support cannot assure the absence of expiratory muscle activity and accurate measurement of driving pressure. Yet, because driving pressure can only be overestimated due to expiratory muscle contraction, in everyday practice, a low driving pressure indicates an absence of global lung over-stretch. A measurement of high driving pressure should prompt further diagnostic workup, such as a measurement of esophageal pressure.
Associations between polymorphisms in IL-10 gene and the risk of viral hepatitis: a meta-analysis
Authors: Zhang Yuanyuan , Chen Lisha , Chen Huixin
Published: July 2020

Background

The relationships between polymorphisms in interleukin-10 (IL-10) gene and the risk of viral hepatitis remain inconclusive. Therefore, the authors conducted so far the very first meta-analysis to robustly assess the relationships between polymorphisms in IL-10 gene and the risk of viral hepatitis by integrating the results of previous works.

Methods

Medline, Embase, Wanfang, VIP and CNKI were searched throughly for eligible studies, and 76 genetic association studies were finally included in this meta-analysis.

Results

We noticed that rs1800871 (− 819 C/T), rs1800872 (− 592 C/A) and rs1800896 (− 1082 G/A) polymorphisms were all significantly associated with the risk of viral hepatitis in Asians, whereas only rs1800896 (− 1082 G/A) polymorphism was significantly associated with the risk of viral hepatitis in Caucasians. In further analyses by disease subtypes, we noticed that the three investigated polymorphisms were all significantly associated with the risk of both HBV and HCV.

Conclusions

This meta-analysis demonstrates that rs1800871 (− 819 C/T), rs1800872 (− 592 C/A) and rs1800896 (− 1082 G/A) polymorphisms may influence the risk of viral hepatitis in Asians, while only rs1800896 (− 1082 G/A) polymorphism may influence the risk of viral hepatitis in Caucasians. In further analyses by disease subtypes, we noticed that the three investigated polymorphisms may influence the risk of both HBV and HCV.
Multifocal cholesterol granulomas of the anterior mediastinum
Authors: Manabe Takehiko , Oka Soichi , Ono Kenji
Published: July 2020

Background

Cholesterol granuloma in the mediastinum is rarely observed, accounting for 1% of all mediastinum tumors. There have been only a few reports of multifocal cholesterol granulomas of the thymus. We herein report a rare case of multifocal cholesterol granuloma in the thymus that was incidentally detected during follow-up of an aortic aneurysm.

Case presentation

The patient was a 70-year-old man with dyslipidemia and hypertension who was referred to our hospital to undergo an operation for chest aortic aneurysm. Preoperative computed tomography (CT) showed 4 lesions in the anterior mediastinum measuring up to 4 cm in size with slight contrast enhancement and spotty calcification. Therefore, a thymoma, bronchogenic cyst, or lymphangioma were considered as the preoperative diagnosis. The patient underwent total thymectomy under thoracotomy followed by aortic arch replacement for the aortic aneurysm. The pathological diagnosis was multifocal cholesterol granulomas in the thymus.

Conclusions

Cholesterol granulomas should be included in the differential diagnosis of cystic tumor in the mediastinum, especially in patients with basal disease such as dyslipidemia and hypertension, which may lead to aortic aneurysm. Furthermore, complete surgical resection and a detailed histological evaluation are important for the accurate diagnosis and treatment.
Comparison of the fluorescence microscopy Cyscope® with light microscopy for malaria diagnosis in a small and active surveillance in Cameroon
Authors: Mbohou Nchetnkou Christian , Nyabeyeu Nyabeyeu Hervé , Kojom Foko Loick P. , Lehman Leopold G.
Published: July 2020

Background

Malaria has a negative impact on the activities of companies in endemic countries especially in Cameroon. In this regard, an increasingly growing number of companies have started to include management of malarious patients in their health policies. In the present study, we will evaluate the diagnostic performances of a fluorescence microscopy (FM), Cyscope® microscope, in the detection of malaria parasites.

Methods

A cross-sectional study was conducted among employees of two companies of the town of Douala on 21 and 22 March 2017. Sociodemographic information of employees was collected using a questionnaire form. Blood samples of ~ 10 μL were collected by venipuncture for the diagnosis of malaria using FM and light microscopy (LM). Performances of FM with respect to sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV), positive and negative likelihood rates (PLR and NLR), accuracy, reliability, and Kappa index were calculated using LM as gold standard.

Results

In total, 442 employees, aged 37.8 ± 9.7 years old on average, were included in the study. Prevalence of malaria using FM and LM was 39.2% and 17%, respectively (p < 0.01). Plasmodium falciparum and P. vivax were the two species involved in malaria infection cases. In terms of developmental stages, 68%, 45.3%, and 1.3% of employees carried gametocytes, trophozoites, and schizonts, respectively. Findings on diagnostic performances of FM were as follows: Se = 84%, Sp = 69.95%, PPV = 63.58%, NPV = 95.5%, accuracy = 89.36%, and reliability = 53.95%. Sensitivity of Cyscope® microscope increased as a function of parasitemia with values ranging from 76.92% at parasitemia between 1 and 500 parasites/μL to 91.11% at parasitemia between 501 and 5000 parasites/μL. The geometric mean parasite density was1850 parasites per μL of blood (range 1600–40,000), and most of employees (60.8%) had moderate parasitemia. The performances of FM were similar between febrile and afebrile patients.

Conclusions

This study showed good performances of Cyscope® microscope and outlines that this diagnostic tool could be used in management of malaria at workplace.
Fibrosing pneumonia – how to diagnose, and how to recognize the etiology?
Authors: Popper Helmut H.-
Published: July 2020

Background

Fibrosing pneumonias are a group of interstitial lung diseases with a different etiologic background and divergent prognosis. They are differentiated into usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), and organizing pneumonia (OP). Some of these entities were initially described by A. Liebow.

Main

In the 90ties the main differences in survival lead to the separation of UIP/IPF as a disease with dismal outcome, from the prognostically better NSIP and OP. Later it was shown that fibrosing NSIP confers an almost identical worse prognosis. Under the heading of pulmologists a classification was created, where the diagnosis has to be established by a multidisciplinary team, based on pattern recognition done by radiologists and pathologists. A clinical diagnosis has to be established based on the patterns: UIP pattern was the basis for IPF, NSIP pattern for the clinical diagnosis NSIP, and organizing pneumonia pattern for the diagnosis of cryptogenic organizing pneumonia. This created confusion, because the pattern UIP was taken almost as synonymous with idiopathic pulmonary fibrosis (IPF). Later on in many articles and classifications the role of the pathologic diagnosis was diminished, because pulmologists based their diagnosis on CT-scan and clinical presentation. This resulted in less tissue biopsies but also delay and misinterpretation of diseases. Even new techniques in tissue biopsies such as cryobiopsy was regarded as unnecessary.

Conclusion

Tissue analysis in fibrosing pneumonias is still the gold standard in making a diagnosis and also evaluating the etiologic background. After an analysis the findings should be discussed in a multidisciplinary board to establish a final diagnosis and a treatment option for the patient.