bluuebunny/crossref_metadata_2025 huggingface dataset:
What hinders and facilitates the implementation of nurse-led interventions in dementia care? A scoping review
Authors: Karrer Melanie , Hirt Julian , Zeller Adelheid , Saxer Susi
Published: April 2020

Background

The implementation of evidence-based interventions for people with dementia is complex and challenging. However, successful implementation might be a key element to ensure evidence-based practice and high quality of care. There is a need to improve implementation processes in dementia care by better understanding the arising challenges. Thus, the aim of this study was to identify recent knowledge concerning barriers and facilitators to implementing nurse-led interventions in dementia care.

Methods

We performed a scoping review using the methodological framework of Arksey and O’Malley. Studies explicitly reporting on the implementation process and factors influencing the implementation of a nurse-led intervention in dementia care in all settings were included. We searched eight databases from January 2015 until January 2019. Two authors independently selected the studies. For data analysis, we used an inductive approach to build domains and categories.

Results

We included 26 studies in the review and identified barriers as well as facilitators in five domains: policy (e.g. financing issues, health insurance), organisation (e.g. organisational culture and vision, resources, management support), intervention/implementation (e.g. complexity of the intervention, perceived value of the intervention), staff (e.g. knowledge, experience and skills, attitude towards the intervention), and person with dementia/family (e.g. nature and stage of dementia, response of persons with dementia and their families).

Conclusions

Besides general influencing factors for implementing nursing interventions, we identified dementia-specific factors reaching beyond already known barriers and facilitators. A pre-existing person-centred culture of care as well as consistent team cultures and attitudes have a facilitating effect on implementation processes. Furthermore, there is a need for interventions that are highly flexible and sensitive to patients’ condition, needs and behaviour.
Cytokine response in human leptospirosis with different clinical outcomes: a systematic review
Authors: Senavirathna Indika , Rathish Devarajan , Agampodi Suneth
Published: April 2020

Background

Leptospirosis is a neglected zoonotic disease which is a major challenge for clinicians and public health professionals in tropical countries. The cytokine storm during the second (immune) phase is thought to be a major contributory factor for the leptospirosis disease severity. We aim to summarize evidence for cytokine response in leptospirosis at different clinical outcomes.

Methods

A systematic review was carried out to examine the cytokine response in leptospirosis patients using relevant scientific databases. Reference lists of the selected articles were also screened. Quality of the selected studies was assessed by using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.

Results

Of the 239 articles retrieved in the initial search, 18 studies fulfilled the selection criteria. India and Thailand have produced the highest number of studies (17% each, n = 3). The majority were comparative cross-sectional studies (72%, n = 13). Overall the quality of the selected studies was fair regardless of few drawbacks such as reporting of sample size and the lack of adjustment for confounders. Microscopic agglutination test (67% - 12/18) and enzyme-linked immunosorbent assay (50% - 9/18) were commonly used for the confirmation of leptospirosis and the measurement of cytokines respectively. IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10 and TNF-α levels were found to be significantly higher in severe than in mild leptospirosis. There were equivocal findings on the association between IL-1β, TNF-α and IL-10/TNF-α ratio and disease severity.

Conclusions

Leptospirosis had a wide-range of elevated cytokines. However, prospective studies in-relation to the onset of the symptom are required to better understand the pathophysiology of cytokine response in leptospirosis.
Diagnosis of severe scrub typhus infection by next-generation sequencing:a case report
Authors: Chen Jie , Zheng Xu-dong , Dai Qi-he , Hong Wei-li , Li You-peng , Chen Rui , Ye Bing-bing , Mo Xiao-jie , Cui Peng , Ruan Zhan-wei
Published: April 2020

Background

Scrub typhus is an acute febrile illness, which was caused by Orientia tsutsugamushi and transmitted through the bite of chiggers. The diagnosis of scrub typhus could be missed diagnosis due to the absence of the pathognomonic eschar.

Case presentation

A 76-year-old man was hospitalized with fever and kidney injury and was diagnosed of hemorrhagic fever with renal syndrome first. However, the situation of the illness deteriorated into refractory septic shock and multiple organ dysfunction rapidly,although the treatment of anti-sepsis was used in 3rd-5th day. Orientia tsutsugamushi was determined to be the causative pathogen by Next-generation sequencing of his plasma sample in 6th day. Then, the patient was treated with doxycycline and azithromycin and recovered quickly.

Conclusions

Next-generation sequencing was a new diagnostic technology and could identify scrub typhus in accurately and fast without the pathognomonic eschar.
Health behaviors of caregivers of childhood cancer survivors: a cross-sectional study
Authors: Cho In Young , Chung Nack-Gyun , Baek Hee Jo , Lee Ji Won , Sung Ki Woong , Shin Dong Wook , Yoo Jung Eun , Song Yun-Mi
Published: April 2020

Background

Caregiving for childhood cancer survivors may be burdensome for caregivers and affect their physical health and health behaviors. However, studies examining health behaviors in caregivers of childhood cancer survivors are scarce. This study aimed to examine health behaviors of caregivers of childhood cancer survivors by comparing them with those of the general population, and analyze associated factors.

Methods

This study included 326 caregivers of childhood cancer survivors recruited from 3 major hospitals in South Korea and 1304 controls from the Korean National Health and Nutritional Examination Survey matched for age, sex, and education level. We compared health behaviors between the two groups by using conditional logistic regression analyses, and investigated factors associated with unhealthy behaviors in caregivers by using multiple logistic regression analyses.

Results

Caregivers were less likely to be physically inactive (aOR: 0.69, 95% CI: 0.51, 0.92) compared to controls, and this was more evident in women (aOR: 0.65, 95% CI: 0.45, 0.94). However, caregivers were more likely to be binge drinkers (aOR: 2.26, 95% CI: 1.73, 2.97), especially if they were men (aOR: 13.59, 95% CI: 8.09, 22.82). Factors associated with unhealthy behaviors in caregivers differed by the type of behavior. Current smoking risk was lower in female caregivers and in those with more comorbidities. Increasing age, female sex, higher education level, and lower household income were associated with lower risk of binge drinking. Higher household income and anxiety were associated with lower risk of physical inactivity, while depression was associated with higher risk of physical inactivity.

Conclusions

Caregivers of childhood cancer survivors were more likely to engage in binge drinking, but less likely to be physically inactive. Strategies to promote adherence to desirable health behaviors in caregivers are needed with consideration of their socioeconomic and clinical factors, such as number of comorbidities.
Trend of disparity between coastland and inland in medical expenditure burden for rural inpatients with malignant tumor in southeast of China from 2007 to 2016
Authors: Fu Rong , Lin Zheng , He Fei , Jiang Yixian , Zheng Zhenquan , Hu Zhijian
Published: April 2020

Background

New Rural Cooperative Medical Scheme (NRCMS) was developed to improve the health security for rural residents. This study aimed to assess the trend of disparity between coastland and inland in medical expenditure burden for rural inpatients with malignant tumor from 2007 to 2016 under the effect of NRCMS.

Methods

The data from medical records of 1,306,895 patients with malignant tumor who had NRCMS in 2932 hospitals was collected. The relative differences [95% confidence intervals (CIs)] between coastland and inland in four medical expense indicators were calculated using generalized linear models to assess the trend of disparity over time.

Results

In total, there were 769,484 (58.88%) coastland patients and 537,411 (41.12%) inland patients. Male and patients aged older than 44 years accounted for 56.87 and 80% of 1,306,895 patients, respectively. After adjusting for gender, age, tumor site and hospital level, coastland patients had higher hospitalization expenses which were all medical expenses incurred during the hospitalization, lower reimbursement ratio and ratio of out-of-pocket expenses to disposable income than inland patients in most years. The surgery expenses of coastland patients were lower than those of inland patients in 2016. The relative differences (95% CIs) between coastland and inland in medical expense indicators were moving closer to 1.0 from 2007 to 2010 among patients without surgery, implying that the disparity between two areas significantly narrowed. The range of change was similar between two areas from 2011 to 2016 whether among patients without or with surgery, implying that the disparity did not significantly change. The disparity between coastland and inland depended on the household income situation. For low-income patients, the differences between two areas in medical expense indicators were not statistically significance in most cases and the disparity between two areas did not significantly change over time.

Conclusions

Under the effect of NRCMS, the medical expenditure burden of rural inpatients reduced but suffering from malignant tumor was still catastrophic. As a whole, the inland patients had heavier medical expenditure burden than coastland patients. Because of economic factors and medical assistance policies, the medical expenditure burden was similar between coastland and inland low-income patients.
Normative values of the retinal macular thickness in a middle eastern population
Authors: AlSaad Mouna M. , Shatarat Amjad T. , AlRyalat Saif Aldeen S.
Published: April 2020

Background

Since the normative value of the retinal macular thickness is undocumented in the Middle East, the aim of this work is to assess the normative values of the macular thickness in healthy eyes in a Middle Eastern population and its relationship with age, sex, and laterality.

Methods

One hundred sixteen individuals were randomly selected from volunteers visiting the Jordan University Hospital in Amman, Jordan. Measurements were obtained using the Fourier domain optical coherence tomography (OCT). Multivariate regression models were developed to obtain predicted normative values with adjustment to candidate variables. In addition, the effect of age, sex and laterality were evaluated.

Results

The average central fovea macular thickness was 229.5 (±30.85) um. The quadratic value of the retinal macular thickness decreased from the superior value of 299.71 (±23.67) um (P = .001) to the inferior value of 296.46 (±28.85) um(P = .001) and a nasal figure of 93.63 (±26.86) um(P = .001). The temporal area has the thinnest value of 293.43 (±30.78) um (P = 0.001). Central thickness was higher in males with a mean variation of 11.67 um (95% CI, 2.41 to 20.93) (p = 0.003). The thickness was highest within 3 mm diameter from the center and decreased towards the periphery Eye sidedness didn’t contribute to variability of the macular thickness. Furthermore, we found a significant difference between age and central macular thickness (p = 0.001), as age was a positive predictor for macular thickness.

Conclusion

Our set of predicted normative data may be used to interrupt measurement of the macular thickness in Middle Eastern population. The average fovea macular thickness among Jordanians is consistent with previously reported values. Normative values from additional Middle Eastern. Population are required to appraise our model.
The effect of health on social capital; a longitudinal observation study of the UK
Authors: Downward Paul , Rasciute Simona , Kumar Harish
Published: April 2020

Background

UK health policy increasingly focusses on health as an asset. This represents a shift of focus away from specific risk factors towards the more holistic capacity by which integrated care assets in the community support improvements in both health and the wider flourishing of individuals. Though the social determinants of health are well known, relatively little research has focussed on the impact of an individual’s health on their social outcomes. This research investigates how improved health can deliver a social return through the development of social capital.

Methods

An observational study is undertaken on 25 years of longitudinal data, from 1991, drawn from the harmonised British Household Panel Survey (BHPS) and Understanding Society Survey (USS). Fixed effects instrumental variable panel data regression analysis is undertaken on individuals. The number of memberships of social organisations, as a measure of structural social capital, is regressed on subjectively measured general health and GHQ12 (Likert) scores. Distinction is drawn between males and females.

Results

Improved general health increases social capital though differences exist between males and females. Interaction effects, that identify the impacts of health for different age groups, reveal that the effect of increased health on social capital is enhanced for males as they age. However, in the case of females increases in general health increase social capital only in connection with their age group. In contrast mental illness generally reduces social capital for males and females, and these effects are reduced through aging.

Conclusions

Investing in health as an asset can improve the social outcomes of individuals. Increasing the outcomes requires tailoring integrated care systems to ensure that opportunities for social engagement are available to individuals and reflect age groups. Targeting improvements in mental health is required, particularly for younger age groups, to promote social capital. The results suggest the importance of ensuring that opportunity for engagement in social and civic organisation be linked to general and mental health care support.
Association between sarcopenia and levels of growth hormone and insulin-like growth factor-1 in the elderly
Authors: Bian Ailin , Ma Yue , Zhou Xinzi , Guo Ying , Wang Wenyi , Zhang Yiran , Wang Xiaofei
Published: April 2020

Background

Age-related sarcopenia is a serious global health issue in elderly individuals and for the community as it induces disability and significant economic burden. The purpose of the study is to understand the factors associated with sarcopenia and the role of growth hormone (GH) and insulin-like growth factor (IGF-1) in the occurrence of sarcopenia.

Methods

Elderly patients (n = 3276) were included in this cross-sectional study. Survey and measurement of body composition (bioelectrical impedance), grip strength, and step speed were performed according to the Asian Working Group on Sarcopenia (AWGS) diagnostic criteria. Hematological and hormonal indicators were compared between patients with and without sarcopenia in order to identify the associated factors.

Results

There were significant differences in the demographic parameters between the sarcopenia and non-sarcopenia groups (all P < 0.05). There were significant differences between the two groups regarding the blood levels of GH, IGF-1, testosterone (T), and mechanical growth factor (MGF) (all P < 0.001). Correlation analyses showed that the appendicular skeletal muscle mass (ASMI) was positively associated with gender and BMI, and with GH, T, IGF-1, MGF, BUN, Cr, and Hb levels, but negatively associated with HDL-C (all P < 0.05). Logistic multivariable regression analysis showed that IGF-1, MGF, BMI, and gender were independently associated with appendicular skeletal muscle mass (ASMI) (all P < 0.05).

Conclusions

GH and IGF-1 are associated with sarcopenia in the elderly. IGF-1 and MGF are independently associated with the reduction of skeletal muscle mass, along with BMI and gender.
Autoimmune polyglandular syndrome type 2 and autoimmune hepatitis with thymoma-associated myasthenia gravis: case report
Authors: Inaba Hidefumi , Ariyasu Hiroyuki , Iwakura Hiroshi , Kurimoto Chiaki , Ueda Yoko , Uraki Shinsuke , Takeshima Ken , Furukawa Yasushi , Morita Shuhei , Nakayama Yoshiaki , Ohashi Takuya , Ito Hidefumi , Nishimura Yoshiharu , Akamizu Takashi
Published: April 2020

Background

Autoimmune polyglandular syndrome type 2 (APS-2) is a rare and complex clinical entity, and little is known about its etiology and progression.

Case presentation

A 52-year-old woman with autoimmune hepatitis (AIH) and bronchial asthma was diagnosed with APS-2; autoimmune Addison’s disease (AD), and Hashimoto’s thyroiditis (HT), and she underwent prednisolone (PSL) treatment. Five months later, she presented ptosis and was diagnosed with thymoma-associated myasthenia gravis (MG). Thymectomy and PSL treatment with immuno-suppressants appeared to ameliorate MG, AD, AIH, HT, and bronchial asthma. HLA typing analysis revealed that the patient had susceptible HLA alleles to MG, AIH, and HT in a Japanese population.

Conclusions

This case suggests common endocrinological and autoimmune aspects of APS-2 and AIH with thymoma-associated MG, which are considered to be extremely rare complications.
Changes of DNA methylation are associated with changes in lung function during adolescence
Authors: Sunny Shadia Khan , Zhang Hongmei , Rezwan Faisal I. , Relton Caroline L. , Henderson A. John , Merid Simon Kebede , Melén Erik , Hallberg Jenny , Arshad S. Hasan , Ewart Susan , Holloway John W.
Published: April 2020

Background

Adolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related CpGs are associated with changes in lung function during adolescence for each gender, and if so, the biological significance of the detected CpGs.

Methods

Genome-scale DNA-M was measured in peripheral blood samples at ages 10 (n = 330) and 18 years (n = 476) from the Isle of Wight (IOW) birth cohort in United Kingdom, using Illumina Infinium arrays (450 K and EPIC). Spirometry was conducted at both ages. A training and testing method was used to screen 402,714 CpGs for their potential associations with lung function. Linear regressions were applied to assess the association of changes in lung function with changes of DNA-M at those CpGs potentially related to lung function. Adolescence-related and personal and family-related confounders were included in the model. The analyses were stratified by gender. Multiple testing was adjusted by controlling false discovery rate of 0.05. Findings were further examined in two independent birth cohorts, the Avon Longitudinal Study of Children and Parents (ALSPAC) and the Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohort. Pathway analyses were performed on genes to which the identified CpGs were mapped.

Results

For females, 42 CpGs showed statistically significant associations with change in FEV1/FVC, but none for change in FEV1or FVC. No CpGs were identified for males. In replication analyses, 16 and 21 of the 42 CpGs showed the same direction of associations among the females in the ALSPAC and BAMSE cohorts, respectively, with 11 CpGs overlapping across all the three cohorts. Through pathway analyses, significant biological processes were identified that have previously been related to lung function development.

Conclusions

The detected 11 CpGs in all three cohorts have the potential to serve as the candidate epigenetic markers for changes in lung function during adolescence in females.
Long non-coding RNA NEAT1/miR-338-3p axis impedes the progression of acute myeloid leukemia via regulating CREBRF
Authors: Feng Song , Liu Na , Chen Xiaoguang , Liu Yufeng , An Jindou
Published: April 2020

Background

Acute myeloid leukemia (AML) is a heterogeneous hematological disease. Our purpose of the research was to investigate the regulatory influence of long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1)/microRNA-338-3p (miR-338-3p)/CREB3 regulatory factor (CREBRF) in AML progression.

Methods

The associated RNA and protein levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Cell growth was assessed through colony formation assay and 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Flow cytometry was exploited to determine the apoptosis rate. Cell migration and invasion were detected by transwell assay. The combination of miR-338-3p and NEAT1 or CREBRF was analyzed via the dual-luciferase reporter assay.

Results

NEAT1 and CREBRF were down-regulated in AML tissues and cells. NEAT1 up-regulation suppressed cell growth, migration and invasion but enhanced apoptosis of AML cells. Inhibition of CREBRF reverted the NEAT1-induced effects on AML cells. Moreover, NEAT1 directly targeted miR-338-3p and miR-338-3p targeted CREBRF. NEAT1/miR-338-3p could affect cellular behaviors of AML cells via the modulation of CREBRF.

Conclusion

NEAT1/miR-338-3p axis repressed the AML progression through regulating CREBRF, which might afford a favorable perspective for the AML treatment molecularly.
Prognostic value of long non-coding RNA GHET1 in cancers: a systematic review and meta-analysis
Authors: Wang Dingding , Zhang Hong , Fang Xiaolian , Zhang Xue , Liu Honggang
Published: April 2020

Background

A number of studies have demonstrated the critical role of long non-coding RNA gastric cancer high expressed transcript 1 (GHET1) in many cancers. This meta-analysis provides an evidence-based evaluation of the prognostic role of GHET1 in cancer.

Materials and methods

Literature searches were conducted in several databases including Medline, Cochrane, EMBASE, CNKI, and Wanfang. The pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were used to evaluate the role of GHET1 in cancer. The study protocol was registered at PROSPERO (ID: CRD42018111252).

Results

Sixteen studies, containing 1315 patients, were analyzed in this meta-analysis. The pooled results indicated that GHET1 overexpression was significantly associated with poor overall survival (OS) and disease-free survival (DFS) in cancer. Moreover, up-regulation of GHET1 expression predicted larger tumor size, positive lymph node metastasis, positive distant metastasis, and advanced TNM (tumor-node-metastases) stage in human cancers.

Conclusion

There is a significant correlation between up-regulation of GHET1 and both poor prognosis and advanced clinicopathological cancer characteristics. GHET1 may be a potential prognostic predictor for human cancers.
Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets
Authors: Belew Sileshi , Suleman Sultan , Duguma Markos , Teshome Henok , Wynendaele Evelien , Duchateau Luc , De Spiegeleer Bart
Published: April 2020

Background

Dissolution of artemether (ART) and lumefantrine (LUM) active pharmaceutical ingredients (APIs) in fixed dose combination (FDC) ART/LUM tablets is one of the critical quality attributes. Thus, the verification of the release profile of ART and LUM from FDC ART/LUM tablets using a robust and discriminatory dissolution method is crucial. Therefore, the aim of this study was to develop and validate an appropriate dissolution method for quality control of FDC ART/LUM tablets.

Methods

The dissolution medium was selected based on saturation solubility data and sink conditions. The effect of agitation speed, pH and surfactant concentration on the release of ART and LUM was evaluated by employing a two-level factorial experiment. The resulting final method was validated for linearity, precision, robustness and API stability. In addition, the discriminatory power of the method was evaluated using expired and unexpired FDC ART/LUM products.

Results

A suitable dissolution profile of FDC ART/LUM tablets was obtained in 900 ml HCl (0.025 N, pH 1.6) with 1%Myrj 52 using paddle method at 100 rpm and 37 °C. ART and LUM were analysed using a HPLC method with UV detection at wavelengths of 210 and 335 nm, respectively. The results from the stability study showed that ART and LUM were sufficiently stable in HCl (0.025 N, pH 1.6) with 1%Myrj 52 at 37 °C. The method was linear (r2 = 0.999) over the concentration range of 6.25–100 μg/ml. The results for precision were within the acceptance limit (%RSD < 2). The percent relative standard deviation (< 2%) and statistically non-significant (p > 0.05) difference in release of ART and LUM observed between deliberately changed dissolution method settings (pH = 1.6 ± 0.2 or agitation speed = 100 ± 2) and optimized dissolution conditions revealed the robustness of the dissolution method. The method was capable to discriminate among different FDC ART/LUM products with different quality.

Conclusions

The developed dissolution method is robust and discriminatory. It can be used in the quality evaluation of FDC ART/LUM tablets.
The circRNA circSEPT9 mediated by E2F1 and EIF4A3 facilitates the carcinogenesis and development of triple-negative breast cancer
Authors: Zheng Xiaying , Huang Mengge , Xing Lei , Yang Rui , Wang Xiaosong , Jiang Rong , Zhang Luyu , Chen Junxia
Published: April 2020

Background

Increasing studies have shown that circRNA is closely related to the carcinogenesis and development of many cancers. However, biological functions and the underlying molecular mechanism of circRNAs in triple-negative breast cancer (TNBC) remain largely unclear so far.

Methods

Here, we investigated the expression pattern of circRNAs in four pairs of TNBC tissues and paracancerous normal tissues using RNA-sequencing. The expression and prognostic significance of circSEPT9 were evaluated with qRT-PCR and in situ hybridization in two TNBC cohorts. The survival curves were drawn by the Kaplan-Meier method, and statistical significance was estimated with the log-rank test. A series of in vitro and in vivo functional experiments were executed to investigate the role of circSEPT9 in the carcinogenesis and development of TNBC. Mechanistically, we explored the potential regulatory effects of E2F1 and EIF4A3 on biogenesis of circSEPT9 with chromatin immunoprecipitation (ChIP), luciferase reporter and RNA immunoprecipitation (RIP) assays. Furthermore, fluorescent in situ hybridization (FISH), luciferase reporter and biotin-coupled RNA pull-down assays were implemented to verify the relationship between the circSEPT9 and miR-637 in TNBC.

Results

Increased expression of circSEPT9 was found in TNBC tissues, which was positively correlated with advanced clinical stage and poor prognosis. Knockdown of circSEPT9 significantly suppressed the proliferation, migration and invasion of TNBC cells, induced apoptosis and autophagy in TNBC cells as well as inhibited tumor growth and metastasis in vivo. Whereas up-regulation of circSEPT9 exerted opposite effects. Further mechanism research demonstrated that circSEPT9 could regulate the expression of Leukemia Inhibitory Factor (LIF) via sponging miR-637 and activate LIF/Stat3 signaling pathway involved in progression of TNBC. More importantly, we discovered that E2F1 and EIF4A3 might promote the biogenesis of circSEPT9.

Conclusions

Our data reveal that the circSEPT9 mediated by E2F1 and EIF4A3 facilitates the carcinogenesis and development of triple-negative breast cancer through circSEPT9/miR-637/LIF axis. Therefore, circSEPT9 could be used as a potential prognostic marker and therapeutical target for TNBC.
The intake assessment of diverse dietary patterns on childhood hypertension: alleviating the blood pressure and lipidemic factors with low-sodium seafood rich in omega-3 fatty acids
Authors: Izadi Anahita , Khedmat Leila , Tavakolizadeh Reza , Mojtahedi Sayed Yousef
Published: April 2020

Background

Childhood hypertension (CH) is related to the dietary intake and diversity of children. The study aimed to assess the critical role of dietary diversity, and seafood long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) in reducing CH among the Iranian community.

Methods

A cross-sectional two-phase study with 7–12-year-old Iranian students was designed. In the initial phase, the socio-demographic characteristics, and blood pressure status (normal, pre-hypertension, and hypertension) based on systolic (SBP) and diastolic (DBP) blood pressure data were assessed. The 24-h dietary recall questionnaire was used to generate the dietary diversity score (DDS, count of consumed food groups) and dietary variety score (DVS, the cumulative number of daily consumed food items). In the second phase, the association between CH reduction and changes in serum 25-hydroxyvitamin D (25OHD), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TG) levels of schoolchildren intervened by a seafood diet rich in omega-3 fatty acids were assessed using the regression analyses.

Results

The pre-hypertension and hypertension prevalence rates were 7.8 and 9.15%, respectively. CH was significantly associated with age, gender, and DDS. A significant inverse association was found between the high intake of seafood and CH (P = 0.032). The gas-chromatography analysis showed the high presence of α-linolenic (ALA, 6.72%), eicosapentaenoic (EPA, 7.62%), docosapentaenoic (DPA, 5.88%), and docosahexaenoic (DHA, 18.52%) acids in the seafood-based diet (p <  0.05). The low blood pressure levels with regular consumption of this healthy-functional diet were significantly associated with a reduction in BMI, LDL, TC, and TG, and a remarkable increase in 25OHD and HDL levels. The multiple linear regression showed that the SBP was highly associated with the TC (p <  0.001; β = 0.464).

Conclusions

The age and DDS were efficient predictors for the different CH status. A regular seafood-rich dietary pattern due to the high LC n-3 PUFAs contents could significantly reduce the obesity-related cardiovascular risk factors.
Preoperative adjuvant therapy for locally advanced and recurrent/metastatic gastrointestinal stromal tumors: a retrospective study
Authors: Qi Jing , Liu He-Li , Ren Feng , Liu Sheng , Shi Wei , Liu Wei-Hang , Cai Gao-Qiang , Liao Guo-Qing
Published: April 2020

Background

Preoperative imatinib mesylate therapy for gastrointestinal stromal tumors (GISTs) is controversial. This study aimed to explore the clinical efficacy and optimal duration of preoperative imatinib mesylate (IM) therapy in patients with locally advanced and recurrent/metastatic GISTs.

Methods

We retrospectively examined patients who received preoperative imatinib mesylate therapy from January 2013 to December 2018 at Xiangya Hospital, Central South University and the Second Xiangya Hospital of Central South University, China. Clinical data, including the results of tests for mutations in KIT and PDGFR, findings from regularly conducted re-examinations, abdominal-enhanced computed tomography/magnetic resonance imaging data, responses to imatinib, progression-free survival, and overall cancer-specific survival, were recorded.

Results

A total of 25 patients were enrolled in our study, including 18 with a locally advanced GIST and 7 with recurrent or metastatic GISTs. Their ages ranged from 22 to 70 years (M:F = 1.6:0.9), with a mean age of 50.48 ± 12.51 years. The tumor locations included the stomach (56.0%), rectum (16.0%), enterocoelic/retroperitoneal sites (12.0%), and the small intestine (12.0%). Based on testing for mutations in KIT and PDGFR, 22 patients received 400 mg/day KIT, and 3 patients received 600 mg/day PDGFR. The median duration of preoperative IM therapy was 8.96 ± 4.81 months, ranging from 3 to 26 months. According to the Choi criteria, 24 patients achieved a partial response (PR), and 1 patient had stable disease (SD). All patients underwent surgery after preoperative IM therapy, and no postoperative complications appeared. The 2-year PFS and 5-year PFS were 92% and 60%, respectively, and the total 5-year cancer-specific survival (CSS) was 92%.

Conclusion

Preoperative imatinib therapy is feasible for locally advanced and recurrent/metastatic GISTs and can effectively shrink the tumor size, allow organ sparing, and avoid extensive organ resection. Moreover, the optimal duration of preoperative IM therapy in patients with locally advanced and recurrent/metastatic GISTs was 8.96 ± 4.81 months, ranging from 3 to 26 months, and gastric GISTs had a better response to preoperative IM therapy than did non-gastric GISTs.
Magnolia extract is effective for the chemoprevention of oral cancer through its ability to inhibit mitochondrial respiration at complex I
Authors: Zhang Qi , Cheng Gang , Pan Jing , Zielonka Jacek , Xiong Donghai , Myers Charles R. , Feng Liang , Shin Song Seok , Kim Young Heui , Bui Dinh , Hu Ming , Bennett Brian , Schmainda Kathleen , Wang Yian , Kalyanaraman Balaraman , You Ming
Published: April 2020

Background

Magnolia extract (ME) is known to inhibit cancer growth and metastasis in several cell types in vitro and in animal models. However, there is no detailed study on the preventive efficacy of ME for oral cancer, and the key components in ME and their exact mechanisms of action are not clear. The overall goal of this study is to characterize ME preclinically as a potent oral cancer chemopreventive agent and to determine the key components and their molecular mechanism(s) that underlie its chemopreventive efficacy.

Methods

The antitumor efficacy of ME in oral cancer was investigated in a 4-nitroquinoline-1-oxide (4NQO)-induced mouse model and in two oral cancer orthotopic models. The effects of ME on mitochondrial electron transport chain activity and ROS production in mouse oral tumors was also investigated.

Results

ME did not cause detectable side effects indicating that it is a promising and safe chemopreventive agent for oral cancer. Three major key active compounds in ME (honokiol, magnolol and 4-O-methylhonokiol) contribute to its chemopreventive effects. ME inhibits mitochondrial respiration at complex I of the electron transport chain, oxidizes peroxiredoxins, activates AMPK, and inhibits STAT3 phosphorylation, resulting in inhibition of the growth and proliferation of oral cancer cells.

Conclusion

Our data using highly relevant preclinical oral cancer models, which share histopathological features seen in human oral carcinogenesis, suggest a novel signaling and regulatory role for mitochondria-generated superoxide and hydrogen peroxide in suppressing oral cancer cell proliferation, progression, and metastasis.
Tumor microenvironment complexity and therapeutic implications at a glance
Authors: Baghban Roghayyeh , Roshangar Leila , Jahanban-Esfahlan Rana , Seidi Khaled , Ebrahimi-Kalan Abbas , Jaymand Mehdi , Kolahian Saeed , Javaheri Tahereh , Zare Peyman
Published: April 2020

The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices.
HDACi mediate UNG2 depletion, dysregulated genomic uracil and altered expression of oncoproteins and tumor suppressors in B- and T-cell lines
Authors: Iveland Tobias S. , Hagen Lars , Sharma Animesh , Sousa Mirta M. L. , Sarno Antonio , Wollen Kristian Lied , Liabakk Nina Beate , Slupphaug Geir
Published: April 2020

Background

HDAC inhibitors (HDACi) belong to a new group of chemotherapeutics that are increasingly used in the treatment of lymphocyte-derived malignancies, but their mechanisms of action remain poorly understood. Here we aimed to identify novel protein targets of HDACi in B- and T-lymphoma cell lines and to verify selected candidates across several mammalian cell lines.

Methods

Jurkat T- and SUDHL5 B-lymphocytes were treated with the HDACi SAHA (vorinostat) prior to SILAC-based quantitative proteome analysis. Selected differentially expressed proteins were verified by targeted mass spectrometry, RT-PCR and western analysis in multiple mammalian cell lines. Genomic uracil was quantified by LC–MS/MS, cell cycle distribution analyzed by flow cytometry and class switch recombination monitored by FACS in murine CH12F3 cells.

Results

SAHA treatment resulted in differential expression of 125 and 89 proteins in Jurkat and SUDHL5, respectively, of which 19 were commonly affected. Among these were several oncoproteins and tumor suppressors previously not reported to be affected by HDACi. Several key enzymes determining the cellular dUTP/dTTP ratio were downregulated and in both cell lines we found robust depletion of UNG2, the major glycosylase in genomic uracil sanitation. UNG2 depletion was accompanied by hyperacetylation and mediated by increased proteasomal degradation independent of cell cycle stage. UNG2 degradation appeared to be ubiquitous and was observed across several mammalian cell lines of different origin and with several HDACis. Loss of UNG2 was accompanied by 30–40% increase in genomic uracil in freely cycling HEK cells and reduced immunoglobulin class-switch recombination in murine CH12F3 cells.

Conclusion

We describe several oncoproteins and tumor suppressors previously not reported to be affected by HDACi in previous transcriptome analyses, underscoring the importance of proteome analysis to identify cellular effectors of HDACi treatment. The apparently ubiquitous depletion of UNG2 and PCLAF establishes DNA base excision repair and translesion synthesis as novel pathways affected by HDACi treatment. Dysregulated genomic uracil homeostasis may aid interpretation of HDACi effects in cancer cells and further advance studies on this class of inhibitors in the treatment of APOBEC-expressing tumors, autoimmune disease and HIV-1.
KLF4 alleviates cerebral vascular injury by ameliorating vascular endothelial inflammation and regulating tight junction protein expression following ischemic stroke
Authors: Zhang Xinyu , Wang Lu , Han Zhenxiang , Dong Jing , Pang Defang , Fu Yuan , Li Longxuan
Published: April 2020

Background

Although inflammatory cell adhesion molecules (CAMs) and anti-inflammation factor Kruppel-like transcription factor (KLF) 4 have all been reported to be induced after cerebral ischemic stroke (CIS), the close temporal and spatial relationship between expressions of CAMs and KLF4 following CIS and whether and how CAMs and KLF-4 contribute to the development of CIS-induced vascular injury are still unclear.

Methods

Here, we first examined the correlation between serum levels of CAMs/KLF4 and infarct volume in acute CIS patients. Then, we determined the relationship between CAMs and KLF4 in mice after focal cerebral ischemia. Finally, we investigated the mechanism of KLF4 in protecting against oxygen-glucose deprivation-induced brain endothelial cell injury.

Results

Our results demonstrated that patients with moderate to severe CIS had higher serum levels of three CAMs including E-selectin, inter-cellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) but lower levels of KLF4 at 48 h after an acute event as compared to patients with minor CIS. The expression levels of three CAMs as well as KLF4 all correlated well with the infarct volume in all the CIS subjects at that time. Although the expressions of three CAMs and KLF4 were all induced in the ischemic hemisphere following focal cerebral ischemia, the peak timing and distribution patterns of their expression were different: the induction of KLF4 lagged behind that of the CAMs in the ischemic penumbra; furthermore, the dual immunofluorescent studies displayed that high expression of KLF4 was always associated with relatively less cerebral vascular endothelial inflammation response in the ischemic hemisphere and vice versa. Mechanistic analyses revealed that KLF4 alleviated CIS-induced cerebral vascular injury by regulating endothelial expressions of CAMs, nuclear factor-kB, and tight junction proteins.

Conclusions

These data indicate that KLF4 confers vascular protection against cerebral ischemic injury, suggesting that circulating CAMs and KLF4 might be used as potential biomarkers for predicting the prognosis of acute ischemic stroke and also providing a new proof of concept and potential targets for future prevention and treatment of CIS.
Associations of an empirical dietary pattern with cardiometabolic risk factors in Malaysian adolescents
Authors: Emi Nor Aishah , Gan Wan Ying , Mohd Shariff Zalilah , Anuar Zaini Azriyanti , Shamsuddin Nurainul Hana , Appukutty Mahenderan , Appannah Geeta
Published: April 2020

Abstracts

Background

This study aimed to identify a dietary pattern (DP) characterised mainly by high intakes of free sugar and other nutrients hypothesised to be associated with obesity such as dietary energy density (DED), percentage of energy from total fat and fibre density in adolescents from three southern states of Peninsular Malaysia, and its associations with cardiometabolic risk factors.

Methods

This is a cross-sectional study among 335 adolescents who provided both dietary information assessed using a validated food frequency questionnaire (FFQ) and biochemical parameters including lipid profile, blood glucose, serum insulin and homeostatic model assessment-insulin resistance (HOMA-IR). Anthropometric measurements included weight (kg), height (cm) and waist circumference (cm), while body mass index (BMI) in kg/m2was estimated, respectively. Reduced rank regression (RRR) identified a DP with percentage of energy from sugar and total fat, DED and fibre density intake as response variables.

Results

The identified ‘high sugar, high fibre, high DED and low fat’ DP was characterised by high intakes of sugar-sweetened beverages, fruits, sweets and low intakes of meat and cereal. Adolescents in the highest tertile of the identified DP had about 3.0 (OR = 2.7; 95%CI: 1.3, 5.6) and 2.0 (OR = 1.9; 95%CI: 1.0, 3.5) times higher odds of having dyslipideamia or elevated total cholesterol and LDL-cholesterol level, respectively compared to adolescents in the lowest tertile DP after adjusting for sex, school location, maternal education, physical activity, dietary misreporting and BMI z-score. This DP was not significantly associated with overweight and obesity.

Conclusions

Higher adherence to a DP characterised mainly by free sugars and DED was associated with greater odds of having dyslipideamia, elevated total cholesterol and LDL-cholesterol levels in Malaysian adolescents.
A case of iatrogenic immunodeficiency-associated colonic lymphoma complicating ulcerative colitis
Authors: Suzuki Kazushi , Ohe Rintaro , Kabasawa Takanobu , Aung Naing Ye , Yano Mitsuhiro , Katsumi Shuichiro , Yanagiya Ryo , Yamamoto Masakazu , Toubai Tomomi , Ishizawa Kenichi , Yamakawa Mitsunori
Published: April 2020

Background

Ulcerative colitis (UC) is one of the major types of inflammatory bowel diseases and is associated with a significantly increased risk of not only lymphoproliferative disorders but also lymphomas, of which most cases are related to the long-term usage of immunosuppressants. Here, we demonstrate a very rare case of other iatrogenic immunodeficiency-associated colonic diffuse large B-cell lymphoma (Oii-DLBCL) complicating UC and rectal perforation. In addition, we reviewed the clinicopathological features of previous cases of DLBCL related to UC.

Case presentation

A 68-year-old man was diagnosed with left-sided UC 26 months prior. Although he was followed by immunosuppressive therapy with azathioprine and infliximab, an emergency total proctocolectomy was performed due to rectal perforation. The resected specimen exhibited irregular wall thickening and elevated multinodular lesions extending from the mid-transverse colon to the rectum, measuring up to 52 cm in length. Histologically, the lesion was diagnosed as Oii-DLBCL and crypt abscess surrounded by mixed inflammatory cell was remained.

Conclusion

Oii-DLBCL complicating UC with rectal perforation is extremely rare. Macro- and microscopic findings are important for early diagnosis of the lesion.
A new technical approach for preparing frozen biological samples for electron microscopy
Authors: Buchner Othmar , Steiner Philip , Andosch Ancuela , Holzinger Andreas , Stegner Matthias , Neuner Gilbert , Lütz-Meindl Ursula
Published: April 2020

Background

Many methodological approaches have focused so far on physiological and molecular responses of plant tissues to freezing but only little knowledge is available on the consequences of extracellular ice-formation on cellular ultrastructure that underlies physiological reactions. In this context, the preservation of a defined frozen state during the entire fixation procedure is an essential prerequisite. However, current techniques are not able to fix frozen plant tissues for transmission electron microscopy (TEM) without interrupting the cold chain. Chemical fixation by glutaraldehyde and osmium tetroxide is not possible at sub-zero temperatures. Cryo-fixation methods, such as high pressure freeze fixation (HPF) representing the state-of-the-art technique for best structural preservation, are not equipped for freezing frozen samples. In order to overcome this obstacle, a novel technical approach for maintaining the cold chain of already frozen plant samples prior and during HPF is presented.

Results

Different algae (Micrasterias denticulata,Klebsormidium crenulatum) and higher plant tissues (Lemnasp.,Ranunculus glacialis,Pinus mugo) were successfully frozen and prepared for HPF at freezing temperatures (− 2 °C, − 5 °C, − 6 °C) within a newly developed automatic freezing unit (AFU), that we manufactured from a standard laboratory freezer. Preceding tests on photosynthetic electron transport and ability to plasmolyse show that the temperatures applied did not impair electron transport in PSII nor cell vitality. The transfer of the frozen specimen from the AFU into the HPF-device and subsequently cryo-fixation were performed without intermediate thawing. After cryo-substitution and further processing, the resulting TEM-micrographs showed excellent ultrastructure preservation of the different organisms when compared to specimens fixed at ambient temperature.

Conclusions

The method presented allows preserving the ultrastructure of plant cells in the frozen state during cryo-fixation. The resulting high quality TEM-images represent an important step towards a better understanding of the consequences of extracellular ice formation on cellular ultrastructure. It has the potential to provide new insights into changes of organelle structure, identification of intracellular injuries during ice formation and may help to understand freezing and thawing processes in plant tissues. It may be combined with analytical TEM such as electron energy loss spectroscopy (EELS), X-ray analyses (EDX) and various other electron microscopic techniques.