bluuebunny/crossref_metadata_2025 huggingface dataset:
The protective effect of iodide intake adjustment and 1,25(OH)2D3 supplementation in rat offspring following excess iodide intake
Authors: Wang Ying , Liu Qing , Dong Hua , Feng Yanni , Raguthu Ciri , Liang Xue , Liu Chen , Zhang Zuncheng , Yao Xiaomei
Published: October 2020

Background:

In this study, we aimed to investigate the effect of iodide intake adjustment, 1,25(OH)2D3 supplementation, or both, on the thyroid gland of rat offspring.

Methods:

The offspring of female rats administered 100 times the normal dose of iodide (100 HI; 750 μg/d) during pregnancy and lactation were divided into four different treatment groups. They were either having their iodide intake adjusted from 100 HI to normal iodide intake (7.5 μg/day) or supplemented with 25-hydroxy vitamin D3 [1,25(OH)2D3; 5 μg·kg−1·day−1], or both, for 4 weeks. Thyroid sodium pertechnetate (Na99mTcO4) uptake percentages were measured using single-photon emission computed tomography, while serum levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and vitamin D3 (VD3) were monitored using enzyme-linked immunosorbent assay. The messenger ribonucleic acid expression of interleukin (IL)-17A, interferon gamma (IFN-γ), and IL-10 in the thyroid gland was measured using quantitative real-time polymerase chain reaction, while the protein expression of thyroid-hormone-receptor α1 (TRα1) and thyroid-hormone-receptor β1 (TRβ1) in the thyroid gland was detected using Western blotting. Haematoxylin and eosin (H & E) and immunofluorescence staining were also used to assess thyroid follicular structure and lymphocytic infiltration in the thyroid glands.

Results:

The immunofluorescence staining showed CD4+ co-localized with TRβ1 or the vitamin D receptor in thyroid gland cells of rats that were continuously treated with 100 HI. Following iodide adjustment, 1,25(OH)2D3 supplementation, or both, an increase in serum levels of FT3, free thyroxine, and VD3, protein expression of TRα1 and TRβ1 in the thyroid gland cells, and Na99mTcO4 thyroid uptake percentages was observed. The mRNA expression levels of IL-17A and IFN-γ, decreased, while the mRNA expression levels of IL-10 increased in the thyroid cells of each treatment group, except the group with continuous 100 HI intake.

Conclusion:

Iodide adjustment, 1,25(OH)2D3 supplementation, or both may increase the serum levels of FT3, FT4, and VD3, as well as the protein expression levels of TRα1 and TRβ1, in thyroid cells. In addition, iodide adjustment, 1,25(OH)2D3 supplementation, or both, may potentially reverse the imbalance in pro-inflammatory and anti-inflammatory cytokines (IL-17A, IFN-γ, and IL-10) caused by 100 HI, which may be beneficial in improving Na99mTcO4 thyroid uptake percentages.
Outcomes in non-ST-segment elevation myocardial infarction patients according to heart failure at admission: Insights from a large trial with systematic early invasive strategy
Authors: Popovic Batric , Sorbets Emmanuel , Abtan Jeremie , Cohen Marc , Pollack Charles V , Bode Christoph , Wiviott Stephen D , Sabatine Marc S , Mehta Shamir R , Ruzyllo Witold , Rao Sunil V , French William J , Kerkar Prafulla , Kiss Robert G , Estrada Jose Luis N , Elbez Yedid , Ducrocq Gregory , Steg Philippe Gabriel ,   the TAO investigators
Published: October 2020

Background

Previous studies published before the era of systematic early invasive strategy have reported a higher mortality in non-ST-segment elevation myocardial infarction patients with heart failure. The aim of our study was to compare the clinical characteristics, outcomes and causes of death of patients according to their heart failure status at admission in a large non-ST-segment elevation myocardial infarction population with planned early invasive management.

Methods

We performed a post-hoc analysis of the Treatment of Acute Coronary Syndrome with Otamixaban randomised trial which included non-ST-segment elevation myocardial infarction patients with systematic coronary angiography within 72 h. Patients were categorised according to presence or absence of heart failure (Killip grade ≥2) at admission.

Results

A total of 13,172 patients were enrolled, of whom 944 (7.2%) had heart failure. At day 30, death occurred in 213 patients (1.6%) and cardiovascular death was the dominant cause of death in both groups ((with vs without heart failure) 78.8% vs 78.4%, p = 0.94). At six months, death occurred in 90/944 (9.5%) patients with heart failure and 258/12228 patients without heart failure (2.1%) (p < 0.001). After adjustment on Global Registry of Acute Coronary Events risk score, heart failure was an independent predictor of all-cause mortality at day 30 (odds ratio: 1.58; 95% confidence interval, 1.06–2.36, p = 0.02) and at day 180 (odds ratio: 1.77; 95% confidence interval, 1.3–2.42, p < 0.001) as well as of ischaemic complications (cardiovascular death, myocardial infarction, stent thrombosis or stroke at day 30 (odds ratio: 1.28; 95% confidence interval, 1.01–1.62, p = 0.04).

Conclusion

Non-ST-segment elevation myocardial infarction patients with heart failure at admission still have worse outcomes than those without heart failure, even with systematic early invasive strategy. Further efforts are needed to improve the prognosis of these high risk patients.
Detection of SARS-CoV-2 RNA in conjunctival swab of a COVID-19 patient: The first report from Bangladesh
Authors: Islam SM Rashed Ul , Akther Tahmina , Mahfuzullah Mohammad Afzal , Nasif Md Abdullah Omar , Jamil Md Shafayet , Mosaddeque Mymuna Binte , Munshi Saif Ullah
Published: October 2020

Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 RNA (SARS-CoV-2 RNA). It usually manifests by fever and/or respiratory illness. Here, we present a case of COVID-19 patient who initially presented ocular symptoms like redness, itching, and watery discharge. Afterward, the patient developed fever and anosmia suggestive of COVID-19 disease. Nasopharyngeal swab and conjunctival swab test for SARS-CoV-2 RNA revealed positive by reverse-transcriptase real-time polymerase chain reaction. The patient was managed symptomatically at home and did not require any hospital admission. On day 12, the patient clinically recovered fully and his follow-up testing for SARS-CoV-2 RNA of both conjunctival swab and nasopharyngeal swab became undetected. This report emphasized that conjunctival mucosa may be considered as a portal of entrance for SARS-CoV-2 RNA in addition to the respiratory route. This study highlighted that any kind of ocular manifestations, such as conjunctival hyperemia, chemosis, watery discharge, periorbital erythema, and burning sensation should never be overlooked for probable COVID-19 in current pandemic settings. Moreover, strict eye protection using goggles/face shield should be used by all health care workers despite any working environment while caring for patients with or without COVID-19-related signs.
Pseudodiverticulum: A rare late complication of the Boari flap procedure for lower ureteric repair
Authors: John Jeff , Bhana Kerisha , Lazarus John , Kesner Ken
Published: October 2020

The Boari bladder flap is a vital tool in the armamentarium of the urologist. It is used to maintain continuity of the urinary system when dealing with diseased segments of the mid and lower ureter. It is, however, associated with long-term complications. We present the case of a 46-year-old woman who developed a rare pseudodiverticulum as a consequence of the procedure. This patient had undergone a right-sided laparoscopic Boari bladder flap for a right distal ureteric stricture secondary to pelvic endometriosis, and presented 10 years later at our urology department with long-standing irritative voiding symptoms and a feeling of incomplete voiding. Radiological and endoscopic investigation revealed the presence of a capacious pseudodiverticulum which was seen on ultrasound to retain a significant amount of urine post micturition and then to empty back into her bladder, strongly suggesting that this was the cause of her sensation of incomplete bladder emptying. She had minimal symptom bother and no recurrent urinary tract infections, calculi or tumour, and it was decided that no further operative management was necessary and that her condition could be managed her conservatively. To the best of our knowledge, this is only the second case describing this rare, long-term complication of a Boari flap.

Level of evidence: Level 5.
Social Media and Fear of Missing Out in Adolescents: The Role of Family Characteristics
Authors: Bloemen Noor , De Coninck David
Published: October 2020

Adolescents are particularly susceptible to development of Fear of Missing Out (FoMO) by using social media. Closely connected to social media addiction, this phenomenon is not exclusively dependent on individual characteristics but is also affected by the family environment. Family structure, parental relationship quality, and parenting style are factors influencing adolescents’ media use, and therefore likely contribute to the development of FoMO. Despite an increasing focus on the relationship between family characteristics and children’s online behavior, not much research has been conducted that relates the family to FoMO. Therefore, this study serves as an exploration. Using online survey data from Flemish and Brussels adolescents aged 13 to 18 years old ( N = 831), we developed a structural equation model. As expected, social media use is positively associated with FoMO. Moreover, family structure and parenting style play an important role in the development of FoMO: being part of a non-intact family, fathers’ parenting style, and perceived high-quality relationships with parents are protective factors for FoMO, while perceived high-quality relationships between parents is a risk factor for FoMO. These results demonstrate that an adolescent’s family context is associated with their experiences of FoMO, and also indicate that more insight in this issue is required.
Why the rising China needs alliances
Authors: Baig Muhammad Ali
Published: October 2020

Alliances remain at the heart of history, since they serve states in achieving geopolitical needs and securing grand strategic necessities. Apart from strategic considerations, the article aspires to highlight the psychological motivation for conceiving and forming alliances. It argues alliances to be the basic instrument in ensuring survival and elaborates the psychological efficacy and utility in employing the same device in gaining and sustaining the status of a functional great power. This article addresses the most significant development in modern times, i.e. rising China and its pursuit to become a pro-active great power, whilst greatly drawing from its strategic history in such endeavours. It explores the ‘China Threat’, and argues that China is likely to enter into alliances based on its geopolitical necessities by engaging its armed forces regionally, most likely in its near abroad. The article interprets China’s Belt and Road Initiative as a soft alliance and predicts the precursors of a military alliance.
Finding globally optimal macrostructure in multiple relation, mixed-mode social networks
Authors: Dabkowski Matthew F , Fan Neng , Breiger Ronald
Published: October 2020

From the outset, computational sociologists have stressed leveraging multiple relations when blockmodeling social networks. Despite this emphasis, the majority of published research over the past 40 years has focused on solving blockmodels for a single relation. When multiple relations exist, a reductionist approach is often employed, where the relations are stacked or aggregated into a single matrix, allowing the researcher to apply single relation, often heuristic, blockmodeling techniques. Accordingly, in this article, we develop an exact procedure for the exploratory blockmodeling of multiple relation, mixed-mode networks. In particular, given (a) [Formula: see text] actors, (b) [Formula: see text] events, (c) an [Formula: see text] binary one-mode network depicting the ties between actors, and (d) an [Formula: see text] binary two-mode network representing the ties between actors and events, we use integer programming to find globally optimal [Formula: see text] image matrices and partitions, where [Formula: see text] and [Formula: see text] represent the number of actor and event positions, respectively. Given the problem’s computational complexity, we also develop an algorithm to generate a minimal set of non-isomorphic image matrices, as well as a complementary, easily accessible heuristic using the network analysis software Pajek. We illustrate these concepts using a simple, hypothetical example, and we apply our techniques to a terrorist network.
Effects of a Physical Exercise Program on Patients Affected with Fibromyalgia
Authors: Sauch Valmaña Glòria , Vidal-Alaball Josep , Poch Pere Roura , Peña Jacobo Mendiroz , Panadés Zafra Robert , Cantero Gómez Francesc Xavier , Ruíz Comellas Anna , Barranco Reixachs David
Published: October 2020

Background:

physical activity has been used for a number of years in the treatment of fibromyalgia (FM). The main objective of this study is to compare the effects of physical activity on 2 groups of women diagnosed with FM in terms of pain, quality of life and the impact of the condition on their daily lives.

Methods:

this was a randomized clinical trial to assess the effects of physical activity performed by subjects assigned to one of 2 groups on the scores of 3 questionnaires, the pain Visual Analog Scale (EVA), the Fibromyalgia Impact Questionnaire (FIQ) and the SF-36 health questionnaire administered before and after the intervention.

Results:

A total of 24 subjects were randomly assigned to each of the 2 study groups. No significant differences were found after the program of 3 months of physical activity ended.

Conclusions:

Our study shows that a physical activity program with duration of less than 3 months does not significantly improve any of the factors studied.
Five-year outcomes of major lower extremity amputation and two-staged admission pathway for new transtibial amputees in a local hospital
Authors: Leong-Pan Hung , Gabriel Chu Chun-Kan , Chun-Hung Chan
Published: October 2020

Background:

Transtibial amputation and subsequent prosthetic fitting can cause prolonged hospital length of stay (LOS). Recently, a two-staged admission pathway for new transtibial amputees was introduced in a local hospital to shorten hospital LOS.

Methods:

A retrospective cohort study was performed to review the 5-year outcomes of major lower extremity amputation in a local hospital and to compare the difference in LOS and functional outcomes between traditional (group 1) and two-staged (group 2) admission pathways for new transtibial amputees.

Results:

The fitting rate was 55% in transtibial amputees, 14% in transfemoral amputees, and only 3.7% in dementia patients. For new transtibial amputees, the mean postoperative LOS was significantly reduced by 32.8 days in group 2. Besides, more patients in group 2 were able to walk without aid.

Conclusion:

LOS for new transtibial amputees can be greatly reduced by the two-staged admission pathway to minimize hospital operational cost.
Chronic Myelomonocytic Leukemia Presenting With Polyserositis and Seropositivity for Rheumatoid Arthritis
Authors: Kunnumpurath Anthony , Desikan Sai Prasad , McClain Charles , Desikan Raman
Published: October 2020

Chronic myelomonocytic leukemia (CMML) is a rare clonal stem cell disorder associated with clinical and pathologic of myelodysplasia and myeloproliferation. Systemic autoimmune/inflammatory disorders (SAID) and polyserositis have been associated with CMML. These manifestations can be observed concomitantly, shortly before diagnosis or anytime along the course of illness. We report a case of myeloproliferative CMML who presented with polyserositis and positive serology for rheumatoid arthritis. Retrospective studies of myelodysplasia/CMML have reported 15% to 25% incidence of SAID. The most commonly observed disorders include systemic vasculitis, connective tissue diseases, polychondritis, seronegative arthritis, and immune thrombocytopenia. SAID does not confer adverse prognosis in retrospective studies. Polyserositis is less common; this may result from leukemic infiltrate or result from autoimmunity. Treatment of serositis includes steroids and cytoreductive agents. Serositis may confer poor prognosis and hypomethylating therapy may improve the outcome.
The Six-Month and One-Year Outcome of a Chronic Disease Self-Management Program Among Older Adults in Macao: A Quasi-Experimental Study
Authors: Leong Sok Man , Lei Wai In , Chan Un Wa
Published: October 2020

Introduction

Promoting older adults to self-manage their chronic conditions is a major focus of the Macao government and healthcare professionals since more than 80% of older adults have suffered chronic conditions.

Objectives

This study evaluated the effect of the Chronic Disease Self-management Program (CDSMP) on self-management behaviors, self-efficacy, health status, and healthcare services utilization among Macao older adults with chronic disease over six months, and assessed whether the intervention effect persisted for one year.

Methods

A longitudinal and quasi-experimental design was used in this study. A total number of 158 older adults with at least one chronic disease were recruited from three Macao community centers. Participants in the study group engaged in a six-session CDSMP in the community centers and participants in the control group received usual care. The Chronic Disease Self-management Questionnaire was used to assess the outcome measures for baseline, six-month and one-year assessment.

Results

The age of subjects ranged from 60 to 88, 64.6% had three or more chronic diseases. The results showed that the subjects in the study group had significant improvement in self-management behaviors, self-efficacy, and some health-related indicators at the point of six months, and these improvements were still observable at the point of one year when comparing to the control group. The results also showed that the study group had a decrease in healthcare services utilization, but there was no significant difference between the two groups.

Conclusion

This study confirmed that the community-dwelling older adults in Macao can acquire positive outcomes in self-management and health-related indicators from the CDSMP. Hence, it is worth promoting this program as a health promotion activity in community.
IBL-202 is synergistic with venetoclax in CLL under in vitro conditions that mimic the tumor microenvironment
Authors: Shen Yandong , Crassini Kyle , Fatima Narjis , O’Dwyer Michael , O’Neill Michael , Christopherson Richard I. , Mulligan Stephen P. , Best O. Giles
Published: October 2020

The B-cell receptor signaling pathway and dysregulation of the Bcl-2 family of proteins play crucial roles in the pathogenesis of chronic lymphocytic leukemia (CLL). Despite significant advances in the treatment of the disease, relapse and drug resistance are not uncommon. In the current study, we investigated the dual PI3/PIM kinase inhibitor IBL-202 in combination with venetoclax as a treatment option for CLL using both primary CLL cells and TP53-deficient OSU-CLL cells generated using the CRISPR-Cas9 system. IBL-202 and venetoclax were highly synergistic against primary CLL cells cocultured with CD40L fibroblasts (combination index [CI], 0.4, at a fractional effect of 0.9) and TP53-knockout (KO) OSU-CLL cells (CI, 0.5, at a fractional effect of 0.9). Synergy between the drugs was consistent, with a significant (P < .05) reduction in the 50% inhibitory concentration for both drugs. IBL-202 and venetoclax in combination induced cell-cycle arrest and slowed the proliferation of both wild-type and TP53-KO cell lines. The drug combination inhibited AKT phosphorylation, reduced expression of Bcl-xL and NF-κB, and increased the Noxa/Mcl-1 ratio. Downregulation of CXCR4 was consistent with inhibition of the SDF-1α–induced migratory capacity of CLL cells. Synergy between IBL-202 and venetoclax against primary CLL cells cultured under conditions that mimic the tumor microenvironment suggests this drug combination may be effective against CLL cells within the lymph nodes and bone marrow. Furthermore, the efficacy of the combination against the TP53-KO OSU-CLL cell line suggests the combination may be a highly effective treatment strategy for high-risk CLL.
Delineation of target expression profiles in CD34+/CD38− and CD34+/CD38+ stem and progenitor cells in AML and CML
Authors: Herrmann Harald , Sadovnik Irina , Eisenwort Gregor , Rülicke Thomas , Blatt Katharina , Herndlhofer Susanne , Willmann Michael , Stefanzl Gabriele , Baumgartner Sigrid , Greiner Georg , Schulenburg Axel , Mueller Niklas , Rabitsch Werner , Bilban Martin , Hoermann Gregor , Streubel Berthold , Vallera Daniel A. , Sperr Wolfgang R. , Valent Peter
Published: October 2020

In an attempt to identify novel markers and immunological targets in leukemic stem cells (LSCs) in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), we screened bone marrow (BM) samples from patients with AML (n = 274) or CML (n = 97) and controls (n = 288) for expression of cell membrane antigens on CD34+/CD38− and CD34+/CD38+ cells by multicolor flow cytometry. In addition, we established messenger RNA expression profiles in purified sorted CD34+/CD38− and CD34+/CD38+ cells using gene array and quantitative polymerase chain reaction. Aberrantly expressed markers were identified in all cohorts. In CML, CD34+/CD38− LSCs exhibited an almost invariable aberration profile, defined as CD25+/CD26+/CD56+/CD93+/IL-1RAP+. By contrast, in patients with AML, CD34+/CD38− cells variably expressed “aberrant” membrane antigens, including CD25 (48%), CD96 (40%), CD371 (CLL-1; 68%), and IL-1RAP (65%). With the exception of a subgroup of FLT3 internal tandem duplication–mutated patients, AML LSCs did not exhibit CD26. All other surface markers and target antigens detected on AML and/or CML LSCs, including CD33, CD44, CD47, CD52, CD105, CD114, CD117, CD133, CD135, CD184, and roundabout-4, were also found on normal BM stem cells. However, several of these surface targets, including CD25, CD33, and CD123, were expressed at higher levels on CD34+/CD38− LSCs compared with normal BM stem cells. Moreover, antibody-mediated immunological targeting through CD33 or CD52 resulted in LSC depletion in vitro and a substantially reduced LSC engraftment in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. Together, we have established surface marker and target expression profiles of AML LSCs and CML LSCs, which should facilitate LSC enrichment, diagnostic LSC phenotyping, and development of LSC-eradicating immunotherapies.
Characteristics of acute ischemic stroke in hospitalized patients in Tibet: a retrospective comparative study
Authors: Lu Yuxuan , Zhuoga Cidan , Jin Haiqiang , Zhu Feiqi , Zhao Yuhua , Ding Zhijie , He Shihua , Du Ailian , Xu Jun , Luo Jingjing , Sun Yongan
Published: October 2020

Background

Numerous studies on acute ischemic stroke (AIS) have been conducted at low-altitude regions, and the related findings have been used to guide clinical management. However, corresponding studies at high altitude are few. This study aimed to analyse the clinical characteristics of AIS patients at high-altitude regions through a hospital-based comparative study between Tibet and Beijing.

Methods

This study included the diagnoses of AIS patients from People’s Hospital of Tibet Autonomous Region (PHOTAR) and Peking University First Hospital (PUFH) between 1 January 2014 and 31 December 2017, where data including patient demographics, treatment time, onset season, risk factors, infarction location, laboratory data, image examination results, treatments, and AIS subtype were collected and compared. Continuous and categorical variables were analysed with a two-sample t-test or Wilcoxon rank sum test and chi-square test, respectively. Significant risk factors were examined with binary logistic regression analysis.

Results

In total, 236 and 1021 inpatients from PHOTAR and PUFH were included, respectively. The PHOTAR patients were younger than the PUFH patients (P < 0.001). Young adult stroke, erythrocytosis, and hyperhomocysteinemia were more frequent in PHOTAR patients (all P < 0.001). Other vascular risk factors, including hypertension, diabetes mellitus, hyperlipidaemia, smoking and alcohol consumption history, were less prevalent in PHOTAR patients than in PUFH patients. The rate of intravenous thrombolysis and the rate of within intravenous thrombolysis window time were also lower in PHOTAR patients (both P < 0.001). The PHOTAR group also tended to have anterior circulation infarction. Erythrocytosis and hyperhomocysteinemia were independent risk factors in PHOTAR, and young adults accounted for a larger proportion of stroke cases.

Conclusion

In Tibet, AIS patients were relatively younger, and anterior circulation infarctions were more common. Erythrocytosis and hyperhomocysteinemia may contribute to these differences. Here, young adult stroke also accounted for a higher proportion, and this may be associated with erythrocytosis. Our findings present the first hospital-based comparative study in Tibet and may contribute to policies for stroke prevention in this region.
Considerations for feature selection using gene pairs and applications in large-scale dataset integration, novel oncogene discovery, and interpretable cancer screening
Authors: Moody Laura , Chen Hong , Pan Yuan-Xiang
Published: October 2020

Background

Advancements in transcriptomic profiling have led to the emergence of new challenges regarding data integration and interpretability. Variability between measurement platforms makes it difficult to compare between cohorts, and large numbers of gene features have encouraged the use black box methods that are not easily translated into biologically and clinically meaningful findings. We propose that gene rankings and algorithms that rely on relative expression within gene pairs can address such obstacles.

Methods

We implemented an innovative process to evaluate the performance of five feature selection methods on simulated gene-pair data. Along with TSP, we consider other methods that retain more information in their score calculations, including the magnitude of gene expression change as well as within-class variation. Tree-based rule extraction was also applied to serum microRNA (miRNA) pairs in order to devise a noninvasive screening tool for pancreatic and ovarian cancer.

Results

Gene pair data were simulated using different types of signal and noise. Pairs were filtered using feature selection approaches, including top-scoring pairs (TSP), absolute differences between gene ranks, and Fisher scores. Methods that retain more information, such as the magnitude of expression change and within-class variance, yielded higher classification accuracy using a random forest model. We then demonstrate two powerful applications of gene pairs by first performing large-scale integration of 52 breast cancer datasets consisting of 10,350 patients. Not only did we confirm known oncogenes, but we also propose novel tumorigenic genes, such as BSDC1 and U2AF1, that could distinguish between tumor subtypes. Finally, circulating miRNA pairs were filtered and salient rules were extracted to build simplified tree ensemble learners (STELs) for four types of cancer. These accessible clinical frameworks detected pancreatic and ovarian cancer with 84.8 and 93.6% accuracy, respectively.

Conclusion

Rank-based gene pair classification benefits from careful feature selection methods that preserve maximal information. Gene pairs enable dataset integration for greater statistical power and discovery of robust biomarkers as well as facilitate construction of user-friendly clinical screening tools.
Why do they do it? A grounded theory study of the use of low-value care among primary health care physicians
Authors: Ingvarsson Sara , Augustsson Hanna , Hasson Henna , Nilsen Per , von Thiele Schwarz Ulrica , von Knorring Mia
Published: October 2020

Background

The use of low-value care (LVC) is widespread and has an impact on both the use of resources and the quality of care. However, few studies have thus far studied the factors influencing the use of LVC from the perspective of the practitioners themselves. The aim of this study is to understand why physicians within primary care use LVC.

Methods

Six primary health care centers in the Stockholm Region were purposively selected. Focus group discussions were conducted with physicians (n = 31) working in the centers. The discussions were coded inductively using a grounded theory approach.

Results

Three main reasons for performing LVC were identified. Uncertainty and disagreement about what not to do was related to being unaware of the LVC status of a practice, guidelines perceived as conflicting, guidelines perceived to be irrelevant for the target patient population, or a lack of trust in the guidelines. Perceived pressure from others concerned patient pressure, pressure from other physicians, or pressure from the health care system. A desire to do something for the patients was associated with the fact that the visit in itself prompts action, symptoms to relieve, or that patients' emotions need to be reassured. The three reasons are interdependent. Uncertainty and disagreement about what not to do have made it more difficult to handle the pressure from others and to refrain from doing something for the patients. The pressure from others and the desire to do something for the patients enhanced the uncertainty and disagreement about what not to do. Furthermore, the pressure from others influenced the desire to do something for the patients.

Conclusions

Three reasons work together to explain primary care physicians’ use of LVC: uncertainty and disagreement about what not to do, perceived pressure from others, and the desire to do something for the patients. The reasons may, in turn, be influenced by the health care system, but the decision nevertheless seemed to be up to the individual physician. The findings suggest that the de-implementation of LVC needs to address the three reasons from a systems perspective.
A modified frozen elephant trunk technique for acute Stanford type A aortic dissection
Authors: Song Shi-bo , Wu Xi-jie , Sun Yong , Cai Shi-hao , Hu Po-yuan , Qiang Hai-feng
Published: October 2020

Background

Acute Stanford type A aortic dissection is often fatal, with a high mortality rate and requiring emergency intervention. Salvage surgery aims to keep the patient alive by addressing severe aortic regurgitation, tamponade, primary tear, and organ malperfusion and, if possible, prevent the late dissection-related complications in the proximal and downstream aorta. Unfortunately, no optimal standard treatment or technique to treat this disease exists. Total arch replacement with frozen elephant trunk technique plays an important role in treating acute type A aortic dissection. We aim to describe a modified elephant trunk technique and report its short-term outcomes.

Methods

From February 2018 to August 2019, 16 patients diagnosed with acute Stanford type A aortic dissection underwent surgery with the modified frozen elephant trunk technique at Xiamen Heart Center (male/female: 9/7; average age: 56.1 ± 7.6 years). All perioperative variables were recorded and analyzed. We measured the diameters of the ascending aorta, aortic arch, and descending aorta on the bifurcation of the pulmonary and abdominal aortas and compared the diameters at admission, before discharge, and 3 months after discharge.

Results

Fifteen patients (93.8%) had hypertension. The primary tears were located in the lesser curvature of the aortic arch and ascending aorta in 5 (31.3%) and 9 patients (56.3%), respectively, and no entry was found in 2 patients (12.5%). The dissection extended to the iliac artery and distal descending aorta in 14 (87.6%) and 2 patients (12.5%), respectively. The duration of cardiopulmonary bypass (CPB), cross-clamping, and antegrade cerebral perfusion were 215.8 ± 40.5, 140.8 ± 32.3, and 55.1 ± 15.2 min, respectively. Aortic valve repair was performed in 15 patients (93.8%). Bentall procedure was performed in one patient (6.3%). Another patient received coronary artery repair (6.3%). The diameters at all levels were greater on discharge than those on admission, except the aortic arch. After 3 months, the true lumen diameter distal to the frozen elephant trunk increased, indicating false lumen thrombosis and/or aortic remodeling.

Conclusions

The modified frozen elephant trunk technique for acute Stanford type A aortic dissection is safe and feasible and could be used for organ malperfusion. Short-term outcomes are encouraging, but long-term outcomes require further investigation.
Discovery of a dual inhibitor of NQO1 and GSTP1 for treating glioblastoma
Authors: Lei Kecheng , Gu Xiaoxia , Alvarado Alvaro G. , Du Yuhong , Luo Shilin , Ahn Eun Hee , Kang Seong Su , Ji Bing , Liu Xia , Mao Hui , Fu Haian , Kornblum Harley I. , Jin Lingjing , Li Hua , Ye Keqiang
Published: October 2020

Background

Glioblastoma (GBM) is a universally lethal tumor with frequently overexpressed or mutated epidermal growth factor receptor (EGFR). NADPH quinone oxidoreductase 1 (NQO1) and glutathione-S-transferase Pi 1 (GSTP1) are commonly upregulated in GBM. NQO1 and GSTP1 decrease the formation of reactive oxygen species (ROS), which mediates the oxidative stress and promotes GBM cell proliferation.

Methods

High-throughput screen was used for agents selectively active against GBM cells with EGFRvIII mutations. Co-crystal structures were revealed molecular details of target recognition. Pharmacological and gene knockdown/overexpression approaches were used to investigate the oxidative stress in vitro and in vivo.

Results

We identified a small molecular inhibitor, “MNPC,” that binds to both NQO1 and GSTP1 with high affinity and selectivity. MNPC inhibits NQO1 and GSTP1 enzymes and induces apoptosis in GBM, specifically inhibiting the growth of cell lines and primary GBM bearing the EGFRvIII mutation. Co-crystal structures between MNPC and NQO1, and molecular docking of MNPC with GSTP1 reveal that it binds the active sites and acts as a potent dual inhibitor. Inactivation of both NQO1 and GSTP1 with siRNA or MNPC results in imbalanced redox homeostasis, leading to apoptosis and mitigated cancer proliferation in vitro and in vivo.

Conclusions

Thus, MNPC, a dual inhibitor for both NQO1 and GSTP1, provides a novel lead compound for treating GBM via the exploitation of specific vulnerabilities created by mutant EGFR.
Letter on Predicting the number of sites needed to deliver a multicentre clinical trial within a limited time frame in the UK
Authors: Greenwood Rosemary , Pell Julie , Foscarini-Craggs Paula , Wale Katharine , Thomas Ian , Bradbury Charlotte
Published: October 2020

When planning a multicentre clinical trial, it can be difficult to predict the time needed to open individual sites, and this in turn impacts on the total number of sites needed, the budget and the time frame for a clinical trial to be delivered successfully. This is of particular importance for funding applications with a limited time frame and budget such as NIHR RfPB. It is more efficient and cost-effective to open the total number of sites needed at the outset of a trial, rather than to respond later to slow site opening and recruitment. Here, we share our experience of successfully delivering a multicentre clinical trial for a rare disease within a limited time frame and budget by approximately doubling the number of sites initially predicted to be needed. We initially predicted 20 sites would be needed to deliver the clinical trial, but early on in the trial, the number of sites was more than doubled to allow successful recruitment of the target sample size within the desired time frame. Of the 48 ethically approved sites, the median time from ethical approval of a site to opening for recruitment was 182 days (95% confidence interval [143 to 245 days]) and ranged from 18 to 613 days. In four (9%) of these sites, part of the delay was due to pharmacy sign off not being given when R&D had issued capacity and capability (C&C). Delays due to pharmacy sign off varied from 10 days to over 3 months delay in two sites (94 days and 102 days). A mathematical solution to the problem of planning a study with a short recruitment window has been given to support the planning and costing of grants with fixed time constraints: number of sites = required sample size divided by (number of eligible patients per site per month times recruitment rate times (the number of months accrual minus 6 months)). We expect these results to help others who are planning multicentre clinical trials in the UK. Ethical approval from NRES Committee South West (IRAS number 225959).

Trial registration

EudraCT Number 2017-001171-23. Registered on 26 June 2017
Use of spinal anaesthesia in neonates and infants in Antananarivo, Madagascar: a retrospective descriptive study
Authors: Randriamizao Harifetra M. R. , Rakotondrainibe Aurélia , Razafindrabekoto Lova D. E. , Ravoaviarivelo Prisca F. , Rajaonera Andriambelo T. , Andriamanarivo Mamy L.
Published: October 2020

Objective

The aim of this study was to present the first cases of spinal anesthesia, in newborns and infants, preterm/ex-prematures, in order to determine its feasibility and its potential harmlessness, in Antananarivo—Madagascar. Indeed, spinal anesthesia is a low cost technique and can limit respiratory complications, postoperative apnea a contrario with pediatric general anesthesia which can lead to perioperative risks.

Results

In a retrospective, descriptive, 7-year (2013 to 2019) period study, conducted in the University Hospital Joseph Ravoahangy Andrianavalona, 69 patients’ data files planned to have spinal anesthesia were recorded. These pediatric patients were predominantly male (sex ratio = 2.8) and 37 [28–52] days old. The smallest anesthetized child weighed 880 g; the youngest was 4 days old. Twenty-seven (27) of them were premature and 20.3% presented respiratory diseases. They were mostly scheduled for hernia repair (90%). Spinal anesthesia was performed, with a Gauge 25 Quincke spinal needle, after 2 [1–2] attempts with hyperbaric bupivacaine of 4 [3.5–4] mg. Failure rate was 5.8%. The heart rate was stable throughout perioperative period and no complications were observed.
Explicit solutions of some equations and systems of mathematical physics
Authors: Slavova Angela , Popivanov Petar
Published: October 2020

This paper deals at first with a fully integrable evolution system of nonlinear partial differential equations (PDEs) which is a generalization of the classical Heisenberg ferromagnet equation. Then the scalar variant of this system is considered. Looking for solutions of special form, the problem of finding explicit solutions of the above-mentioned equations is reduced to the global solvability of overdetermined real-valued systems of nonlinear PDEs. In many cases particular solutions which are not solitons are expressed by classical functions including some special ones as Jacobi elliptic functions, Legendre elliptic functions, and Weierstrass normal elliptic integrals. A geometrical visualization of several solutions is also proposed.
Identification of repurposable cytoprotective drugs in vanishing white matter disease patient-derived cells
Authors: Ng Neville , Cabral-da-Silva Mauricio Castro , Maksour Simon , Berg Tracey , Engel Martin , Silva Dina M. , Do-Ha Dzung , Lum Jeremy S. , Muñoz Sonia Sanz , Suarez-Bosche Nadia , Stevens Claire H. , Ooi Lezanne
Published: October 2020

Background

Vanishing white matter disease (VWMD) is a rare disease caused by mutations of the guanine exchange factor eIF2B. VWMD typically presents with juvenile onset, and there are few treatments for the disease. Recent progress in the field has established mitochondrial dysfunction and endoplasmic reticulum (ER) stress to be strongly implicated in observed glial cell pathology. Drug repurposing offers a rapid approach toward translation of therapeutics using already-licensed drugs.

Objective

The aim of this study was to use fibroblasts and induced pluripotent stem cell (iPSC)-derived astrocytes from patients bearing the EIF2B5R113H/A403V or EIF2B2G200V/E213G VWMD mutations to identify potential repurposable FDA-approved drugs based on in vitro assays.

Methods

Cell viability in the presence or absence of stress was assessed by resazurin reduction activity and assays for mitochondrial membrane potential and oxidative stress by tetramethylrhodamine and dichlorofluorescein-based assays, respectively. Integrated stress response markers, including eIF2α phosphorylation, GADD34 and CHOP were quantified by fluorescent western blot.

Results

Dysregulated GADD34 and CHOP were identified in patient fibroblasts and iPSC-derived astrocytes under induced stress conditions. A drug screen from a 2400 FDA-approved drug library with EIF2B5R113H/A403V VWMD patient fibroblasts identified 113 anti-inflammatory drugs as a major class of hits with cytoprotective effects. A panel of candidate drugs, including berberine, deflazacort, ursodiol, zileuton, guanabenz and Anavex 2–73, and preclinical ISRIB, increased cell survival of EIF2B5R113H/A403V or EIF2B2G200V/E213G VWMD astrocytes, and were further investigated for their effect on the integrated stress response and mitochondrial stress. Ursodiol demonstrated capacity to ameliorate oxidative stress and loss of mitochondrial membrane potential in VWMD patient iPSC-derived astrocytes in the presence or absence of stress conditions.

Conclusion

Patient-derived cells can be used to identify cellular phenotypes and for large-scale drug screening. Anti-inflammatory compounds, such as berberine, deflazacort, ursodiol and zileuton are potentially repurposable drug candidates for VWMD that should be further investigated for translation in vivo.
The roles of iodized oil-based lymphangiography and post-lymphangiographic computed tomography for specific lymphatic intervention planning in patients with postoperative lymphatic fistula: a literature review and case series
Authors: Pan F. , Loos M. , Do T. D. , Richter G. M. , Kauczor H. U. , Hackert T. , Sommer C. M.
Published: October 2020

In the management of patients with postoperative lymphatic fistula (LF) in different locations, iodized oil-based lymphangiography (LAG) from trans-pedal or intranodal route is an established diagnostic approach with the potential to plan further interventional treatments. However, specific lymphatic interventions are indicated depending on different locations and morphologies of the LF. After a systematic literature review, four types of interventions can be considered, including direct leakage embolization/sclerotherapy (DLE/DLS), percutaneous afferent lymphatic vessel embolization (ALVE), percutaneous afferent lymphatic vessels disruption/sclerotherapy (ALVD/ALVS), and trans-afferent nodal embolization (TNE). In the iodized oil-based LAG, three potential lymphatic targets including confined leakage, definite afferent LVs, and definite closest afferent LNs should be comprehensively assessed. For optimal prospective treatment planning for LF, iodized oil-based post-lymphangiographic computed tomography (post-LAG CT) is a useful complement to the conventional iodized oil-based LAG, which can be performed easily after LAG. This review article summarized the current evidence of the specific lymphatic interventions in patients with postoperative LF and explored the potential benefits of post-LAG CT in the intervention planning from a case series.
Reliability and validity of 3 different Chinese versions of the Oxford knee score (OKS)
Authors: Ngwayi James Reeves Mbori , Tan Jie , Liang Ning , Porter Daniel Edward
Published: October 2020

Background

Different Chinese versions of the Oxford Knee Score (OKS) are available for knee arthritis assessment. These include the Malaysian, Hong Kong and Singaporean Chinese versions with slight variations in wordings and use of Cantonese in the Hong Kong Version. This study evaluated the validity and reliability of the different Chinese OKS versions in Mainland China.

Methods

One hundred ninety four China mainland-based patients participated in the study, each being diagnosed with knee osteoarthritis. The patients were randomly assigned into 3 groups: Group A completed the Malaysian OKS; Group B completed the Singaporean OKS; Group C completed the Hong Kong OKS. Participants also completed the 36-item Short Form Survey (SF 36). The electronic versions of the questionnaires completed by the patients were sent to smart devices via a social media platform.

Results

Interclass coefficients for test-retest reliability of the groups were 0.917 in group A, 0.921 in group B, 0.824 in group C. Cronbach alpha results for internal consistency of the 3 groups were: 0.912 in group A, 0.896 in group B, 0.846 in group C. Spearson correlation results with individual SF-36 domains were as follows: Group A showed strong negative correlations with bodily pain and physical function domains; group B exhibited moderate negative correlations with the bodily pain and physical function domains; group C revealed strong negative correlations with the bodily pain and physical function domains and weak negative correlations with vitality domain.

Conclusions

Different Chinese versions of the OKS showed good reliability and convergent validity in mainland samples of patients with knee osteoarthritis, supporting their use in research and other related studies.