bluuebunny/crossref_metadata_2025 huggingface dataset:
Renibacterium salmoninarum and Mycobacterium spp.: two bacterial pathogens present at low levels in wild brown trout (Salmo trutta fario) populations in Austrian rivers
Authors: Delghandi M. R. , Menanteau-Ledouble S. , Waldner K. , El-Matbouli M.
Published: February 2020

Background

Renibacterium salmoninarumandMycobacteriumsp. are important bacterial pathogens of fish.R. salmoninarumis the causative agent of bacterial kidney disease, a Gram-positive bacterium mostly known for causing chronic infections in salmonid fish, while multiple species belonging to theMycobacteriumgenus have been associated with mycobacteriosis in fish as well as in human. The objective of this study was to determine the prevalence of these two bacterial pathogens in populations of wild brown trout (Salmo trutta fario) in four rivers (Kamp, Wulka, Traun and Ybbs) in Austria.

Results

A total of 457 kidney samples were examined for both bacterial agents using nested and conventional PCR as well as bacterial cultivation on KDM-2, histological examination and immunohistochemistry. Molecular evidence showed an estimated prevalence level of 0.94% forR. salmoninarumin 2017 while the bacterium could not be detected in 2018 and histology showed signs consistent with a low-level chronic inflammation in the kidney of infected fish. Similarly, no fish were found positive forMycobacteriumin 2017 but in 2018, the prevalence was found to be 37.03% in the Kamp river (4.08% across all rivers). The sequencing data confirmed that these fish carriedMycobacteriumsp. although the precise species ofMycobacteriumcould not be ascertained.

Conclusions

This survey constitutes the first insight into the prevalence rate ofR. salmoninarumandMycobacteriumsp. in wild brown trout (Salmo trutta fario)populations in Austria. Both of these pathogens were only detected in the summer months (June and July), which might suggest that the stress linked to increased water temperature could act as stressor factor and contribute to the outbreak of these diseases. The age of the fish might also play a role, especially in the case ofMycobacteriumsp. as all the infected fish were in their first summer (June).
Comparison of DNA methylation profiles from saliva in Coeliac disease and non-coeliac disease individuals
Authors: Hearn Nerissa L. , Chiu Christine L. , Lind Joanne M.
Published: February 2020

Background

Coeliac disease (CD) is a autoimmune disease characterised by mucosal inflammation in the small intestine in response to dietary gluten. Genetic factors play a key role with CD individuals carrying either the HLA-DQ2 or HLA-DQ8 haplotype, however these haplotypes are present in half the general population making them necessary but insufficient to cause CD. Epigenetic modifications, including DNA methylation that can change in response to environmental exposure could help to explain how interactions between genes and environmental factors combine to trigger disease development. Identifying changes in DNA methylation profiles in individuals with CD could help discover novel genomic regions involved in the onset and development of CD.

Methods

The Illumina InfiniumMethylation450 Beadchip array (HM450) was used to compare DNA methylation profiles in saliva, in CD and non-CD affected individuals. CD individuals who had been diagnosed at least 2 years previously; were on a GFD; and who were currently asymptomatic; were compared to age and sex-matched non-CD affected healthy controls. Bisulphite pyrosequencing was used to validate regions found to be differentially methylated. These regions were also validated in a second larger cohort of CD and non-CD affected individuals.

Results

Methylation differences within the HLA region at HLA-DQB1 were identified on HM450 but could not be confirmed with pyrosequencing. Significant methylation differences near the SLC17A3 gene were confirmed on pyrosequencing in the initial pilot cohort. Interestingly pyrosequencing sequencing of these same sites within a second cohort of CD and non-CD affected controls produced significant methylation differences in the opposite direction.

Conclusion

Altered DNA methylation profiles appear to be present in saliva in CD individuals. Further work to confirm whether these differences are truly associated with CD is needed.
Reduced airway levels of fatty-acid binding protein 4 in COPD: relationship with airway infection and disease severity
Authors: Perea Lídia , Rodrigo-Troyano Ana , Cantó Elisabet , Domínguez-Álvarez Marisol , Giner Jordi , Sanchez-Reus Ferran , Villar-García Judit , Quero Sara , García-Núñez Marian , Marín Alicia , Monsó Eduard , Faner Rosa , Agustí Alvar , Vidal Silvia , Sibila Oriol
Published: February 2020

Background

For still unclear reasons, chronic airway infection often occurs in patients with Chronic Obstructive Pulmonary Disease (COPD), particularly in those with more severe airflow limitation. Fatty-acid binding protein 4 (FABP4) is an adipokine involved in the innate immune response against infection produced by alveolar macrophages (Mɸ). We hypothesized that airway levels of FABP4 may be altered in COPD patients with chronic airway infection.

Methods

In this prospective and controlled study we: (1) compared airway FABP4 levels (ELISA) in induced sputum, bronchoalveolar lavage fluid (BALF) and plasma samples in 52 clinically stable COPD patients (65.2 ± 7.9 years, FEV1 59 ± 16% predicted) and 29 healthy volunteers (55.0 ± 12.3 years, FEV1 97 ± 16% predicted); (2) explored their relationship with the presence of bacterial airway infection, defined by the presence of potentially pathogenic bacteria (PPB) at ≥103 colony-forming units/ml in BALF; (3) investigated their relationship with the quantity and proportion of Mɸ in BALF (flow cytometry); and, (4) studied their relationship with the severity of airflow limitation (FEV1), GOLD grade and level of symptoms (CAT questionnaire).

Results

We found that: (1) airway levels of FABP4 (but not plasma ones) were reduced in COPD patients vs. controls [219.2 (96.0–319.6) vs. 273.4 (203.1–426.7) (pg/ml)/protein, p = 0.03 in BALF]; (2) COPD patients with airway infection had lower sputum FABP4 levels [0.73 (0.35–15.3) vs. 15.6 (2.0–29.4) ng/ml, p = 0.02]; (3) in COPD patients, the number and proportion of Mɸ were positively related with FABP4 levels in BALF; (4) BALF and sputum FABP4 levels were positively related with FEV1, negatively with the CAT score, and lowest in GOLD grade D patients.

Conclusions

Airway FABP4 levels are reduced in COPD patients, especially in those with airway infection and more severe disease. The relationship observed between Mɸ and airway FABP4 levels supports a role for FABP4 in the pathogenesis of airway infection and disease severity in COPD.
Neuromuscular blocking agents for acute respiratory distress syndrome: an updated meta-analysis of randomized controlled trials
Authors: Zheng Zhongjun , Jiang Libing , Zhang Song , Guervilly Christophe , Zhang Mao , Feng Xia , Ding Jianbo
Published: February 2020

Backgrounds

The aim of this study is investigating the benefits and harms of neuromuscular blocking agents (NMBAs) in patients with acute respiratory distress syndrome (ARDS).

Methods

We comprehensively searched PubMed, EMBASE, and Cochrane library for randomized controlled trials comparing NMBAs to any other comparator. We pooled data using relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals. We assessed the quality of included studies using the Cochrane tool and levels of evidence using the GRADE method.

Results

Finally, six RCTs (n = 1557 patients) were eligible for analysis. The results showed NMBAs use was not associated with reduced 28 days mortality (RR 0.78; 95% CI, 0.58 to 1.06; P = 0.11), 90 days mortality (RR, 0.92; 95% CI, 0.81 to 1.04; P = 0.16), and intensive care unit (ICU) mortality (RR, 0.90; 95% CI, 0.79 to 1.03; P = 0.13) in patients with ARDS. However, 21–28 days mortality was slightly lower in patients received NMBAs (RR 0.73; 95% CI, 0.54 to 0.99; P = 0.04; I2 = 53%). Besides, NMBAs use could improve the PaO2/FiO2 ratio at 48 and 72 h, decrease plateau pressure and PEEP at 72 h. Additionally, NMBAs had no significant effects on days free of ventilation at day 28 (WMD, 0.55; 95% CI, − 0.46 to 1.57; P = 0.29), days not in ICU at day 28 (WMD, 0.12; 95% CI, − 0.85 to 1.08; P = 0.82), ICU-acquired weakness (RR, 1.23; 95% CI, 0.99 to 1.93; P = 0.06). Finally, NMBAs use was associated with a lower risk of barotrauma (RR, 0.55; 95% CI, 0.35 to 0.85; P = 0.007).

Conclusion

In patients with respiratory distress syndrome, NMBAs may be beneficial in reverse refractory hypoxemia and may be associated with reduced short-term mortality and incidence of barotrauma. However, there is no significant effects of NMBAs on mid-term and long-term mortality, and further studies are required.
Impact of COPD and anemia on motor and cognitive performance in the general older population: results from the English longitudinal study of ageing
Authors: Padberg Inken , Schneider Alice , Rohmann Jessica Lee , Kelley Sean Walter , Grittner Ulrike , Siegerink Bob
Published: February 2020

Background

Cognitive and motor-performance decline with age and the process is accelerated by decline in general health. In this study, we aimed to estimate the effects of COPD and HB levels on cognitive and motor performance in the general older population and assess potential interaction.

Methods

The English Longitudinal Study of Aging is a population-based cohort study including measurements of lung-function and HB levels together with cognitive and motor performance testing. Data were collected from 5709 participants including three measurement time over eight years. COPD was defined using lung-function-parameters and clinical symptoms. HB was assessed continuously and low HB was defined using clinical anemia cutoffs. Linear mixed-effects regression models were used to quantify the associations of COPD and HB with outcome measures, both individually and in combination.

Results

Participants with both low HB and COPD demonstrated worse motor performance compared to individuals with only one exposure, resulting in up to 1 s (95%CI, 0.04–1.8) longer time needed to complete the five times sit to stand task than what would be expected based on purely additive effects. Additionally in individuals with COPD, the time to complete the motor-performance task per unit decrease in continuous HB levels was longer than in participants without COPD after full adjustment for confounding (up to 1.38 s/unit HB level, 95% CI: 0.65–2.11).

Conclusion

In persons with COPD low HB levels may contribute to low motor-performance in a supra additive fashion. Further studies should re-evaluate whether earlier treatment of lower HB in these individuals might be beneficial.
Positive effect of dapagliflozin on left ventricular longitudinal function for type 2 diabetic mellitus patients with chronic heart failure
Authors: Tanaka Hidekazu , Soga Fumitaka , Tatsumi Kazuhiro , Mochizuki Yasuhide , Sano Hiroyuki , Toki Hiromi , Matsumoto Kensuke , Shite Junya , Takaoka Hideyuki , Doi Tomofumi , Hirata Ken-ichi
Published: February 2020

Background

The effect of sodium glucose cotransporter type 2 (SGLT2) inhibitor on left ventricular (LV) longitudinal myocardial function in type 2 diabetes mellitus (T2DM) patients with heart failure (HF) has remained unclear.

Methods

We analyzed data from our previous prospective multicenter study, in which we investigated the effect of the SGLT2 inhibitor dapagliflozin on LV diastolic functional parameters of T2DM patients with stable HF at five institutions in Japan. Echocardiography was performed at baseline and 6 months after administration of dapagliflozin. LV diastolic function was defined as the ratio of mitral inflow E to mitral e′ annular velocities (E/e′). LV longitudinal myocardial function was assessed as global longitudinal strain (GLS), which in turn was determined as the averaged peak longitudinal strain from standard LV apical views.

Results

E/e′ significantly decreased from 9.3 to 8.5 cm/s 6 months after administration of dapagliflozin (p = 0.020) as previously described, while GLS showed significant improvement from 15.5 ± 3.5% to 16.9 ± 4.1% (p < 0.01) 6 months after administration of dapagliflozin. Furthermore, improvement of GLS in HF with preserved ejection fraction patients was more significant from 17.0 ± 1.9% to 18.7 ± 2.0% (p < 0.001), compared to that in HF with mid-range ejection fraction and HF with reduced ejection fraction patients from 14.4 ± 2.4% to 15.5 ± 1.8% (p = 0.06) and from 8.1 ± 1.5% to 7.8 ± 2.1% (p = 0.44), respectively. It was noteworthy that multiple regression analysis showed that the change in GLS after administration of dapagliflozin was the only independent determinant parameters for the change in E/e′ after administration of dapagliflozin.

Conclusion

Dapagliflozin was found to be associated with improvement of LV longitudinal myocardial function, which led to further improvement of LV diastolic function of T2DM patients with stable HF. GLS-guided management may thus lead to improved management of T2DM patients with stable HF.
Redesign and reconstruction of a steviol-biosynthetic pathway for enhanced production of steviol in Escherichia coli
Authors: Moon Jun Ho , Lee Kunjoong , Lee Jun Ho , Lee Pyung Cheon
Published: February 2020

Background

Steviol glycosides such as stevioside have attracted the attention of the food and beverage industry. Recently, efforts were made to produce these natural sweeteners in microorganisms using metabolic engineering. Nonetheless, the steviol titer is relatively low in metabolically engineered microorganisms, and therefore a steviol-biosynthetic pathway in heterologous microorganisms needs to be metabolically optimized. The purpose of this study was to redesign and reconstruct a steviol-biosynthetic pathway via synthetic-biology approaches in order to overproduce steviol in Escherichia coli.

Results

A genome-engineered E. coli strain, which coexpressed 5′ untranslated region (UTR)-engineered geranylgeranyl diphosphate synthase, copalyl diphosphate synthase, and kaurene synthase, produced 623.6 ± 3.0 mg/L ent-kaurene in batch fermentation. Overexpression of 5′-UTR–engineered, N-terminally modified kaurene oxidase of Arabidopsis thaliana yielded 41.4 ± 5 mg/L ent-kaurenoic acid. Enhanced ent-kaurenoic acid production (50.7 ± 9.8 mg/L) was achieved by increasing the cellular NADPH/NADP+ ratio. The expression of a fusion protein, UtrCYP714A2-AtCPR2 derived from A. thaliana, where trCYP714A2 was 5′-UTR–engineered and N-terminally modified, gave 38.4 ± 1.7 mg/L steviol in batch fermentation.

Conclusions

5′-UTR engineering, the fusion protein approach, and redox balancing improved the steviol titer in flask fermentation and bioreactor fermentation. The expression engineering of steviol-biosynthetic enzymes and the genome engineering described here can serve as the basis for producing terpenoids—including steviol glycosides and carotenoids—in microorganisms.
CircZDHHC20 represses the proliferation, migration and invasion in trophoblast cells by miR-144/GRHL2 axis
Authors: Zhou Bing , Zhang Xia , Li Ting , Xie Rongping , Zhou Jianbin , Luo Yu , Yang Chunfen
Published: February 2020

Background

Preeclampsia (PE) is a prevalent pregnancy disorder that has been one of the leading causes of maternal and perinatal mortality worldwide. Circular RNAs (circRNAs) have recently considered as important regulators in PE pathogenesis. In the current study, we aimed to explore the impact and mechanisms of circRNA zinc finger DHHC-type palmitoyltransferase 20 (circZDHHC20) in PE pathogenesis.

Methods

RNase R assay and reverse transcription with Oligo(dT)18 primers were performed to confirm that circZDHHC20 was indeed circular transcript. The expression of circZDHHC20, grainyhead-like 2 (GRHL2) and miR-144 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Subcellular localization assay was used to determine whether circZDHHC20 was predominantly present in the cytoplasm. The target correlations between miR-144 and circZDHHC20 or GRHL2 were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, migration, and invasion were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetr-azolium (MTS), wound healing and transwell assays, respectively. Western blot was used for the quantification of GRHL2 protein level.

Results

Our data indicated that circZDHHC20 was up-regulated and miR-144 was down-regulated in PE placenta. CircZDHHC20 sequestered miR-144 by acting as a miR-144 sponge. CircZDHHC20 overexpression repressed trophoblast cell proliferation, migration, and invasion, while its knockdown exerted opposite effects. Moreover, miR-144 mediated the regulation of circZDHHC20 on trophoblast cell behaviors. GRHL2 was directly targeted and inhibited by miR-144. MiR-144 exerted regulatory effects on trophoblast cell proliferation, migration and invasion by GRHL2. Furthermore, circZDHHC20 modulated GRHL2 expression through sponging miR-144.

Conclusion

Our study suggested that a high level of circZDHHC20 inhibited the proliferation, migration, and invasion in trophoblast cells at least partially through sponging miR-144 and up-regulating GRHL2, providing a novel mechanism of PE pathogenesis.
Knockdown of lncRNA SNHG16 suppresses multiple myeloma cell proliferation by sponging miR-342-3p
Authors: Yang Xi , Huang Hongming , Wang Xinfeng , Liu Haiyan , Liu Hong , Lin Zenghua
Published: February 2020

Background

Aberrant expression of long non-coding RNAs (lncRNAs) is closely associated with development and prognosis of human cancers. LncRNA SNHG16 is reportedly involved in human cancer; however, its roles in multiple myeloma (MM) remain unclear.

Methods

In this study, we investigated the function and molecular mechanisms of SNHG16 in MM. MM cells were transfected with si-SNHG16 or si-NC. SNHG16 expression levels was measured by qRT-PCR. Cell proliferation was monitored using the MTS. Flow cytometry assay was performed to measure the cell cycle and apoptosis. Luciferase reporter assay were performed to confirm the sponged miRNAs of SNHG16.

Results

SNHG16 expression was up-regulated in MM tissues. SNHG16 knockdown suppressed cell proliferation, arrested cell cycle transition from G1 to S phase, and promoted the apoptosis of MM cells. Moreover, SNHG16 knockdown promoted cleaved-Caspase-3, cleaved-Caspase-9, Foxa3a, and Bax expression, while markedly inhibiting CCND1, Bcl-2, Cyclin D1, PI3K, and p-AKT expression in MM cells. miR-342-3p was a direct target of SNHG16. SNHG16 knockdown significantly increased miR-342-3p expression in MM cells. Overexpression miR-342-3p markedly suppressed cell proliferation, arrested cell cycle transition from G1 to S phase, and promoted apoptosis of MM cells. Overexpression of miR-342-3p markedly promoted cleaved-Caspase-3/-9, Foxa3a, and Bax expression, and inhibited CCND1, Bcl-2, Cyclin D1, PI3K, and p-AKT expression in MM cells. Additionally, repression of miR-342-3p could rescue the effect of SNHG16 knockdown on MM cell proliferation, cycle arrest, apoptosis, and related protein expression.

Conclusion

Knockdown of lncRNA SNHG16 suppresses MM cell proliferation by sponging miR-342-3p, implicating SNHG16 as a novel therapeutic target for MM.
Plasmodium falciparum pre-erythrocytic stage vaccine development
Authors: Molina-Franky Jessica , Cuy-Chaparro Laura , Camargo Anny , Reyes César , Gómez Marcela , Salamanca David Ricardo , Patarroyo Manuel Alfonso , Patarroyo Manuel Elkin
Published: February 2020

Worldwide strategies between 2010 and 2017 aimed at controlling malarial parasites (mainly Plasmodium falciparum) led to a reduction of just 18% regarding disease incidence rates. Many biologically-derived anti-malarial vaccine candidates have been developed to date; this has involved using many experimental animals, an immense amount of work and the investment of millions of dollars. This review provides an overview of the current state and the main results of clinical trials for sporozoite-targeting vaccines (i.e. the parasite stage infecting the liver) carried out by research groups in areas having variable malaria transmission rates. However, none has led to promising results regarding the effective control of the disease, thereby making it necessary to complement such efforts at finding/introducing new vaccine candidates by adopting a multi-epitope, multi-stage approach, based on minimal subunits of the main sporozoite proteins involved in the invasion of the liver.
The sensitivity of different methods for detecting abnormalities in auditory nerve function
Authors: Lu Tianhao , Li Qiang , Zhang Chen , Chen Min , Wang Zhengming , Li Shufeng
Published: February 2020

Background

Cochlear implants (CIs) have become important for the treatment of severe-to-profound sensorineural hearing loss (SNHL). Meanwhile, electrically evoked compound action potentials (ECAPs) and electrically evoked auditory brainstem responses (EABRs), which can be examined and evaluated with minimal patient cooperation, have become more reliable for tone measurement and speech recognition postoperatively. However, few studies have compared the electrophysiological characteristics of the auditory nerve using ECAPs and EABRs under different functional states of the auditory nerve (FSANs). We used guinea pig models in which six electrodes were implanted unilaterally with continuous electrical stimulation (ES) for 4 h. The amplitude growth functions (AGFs) of the alternating polarity ECAP (AP-ECAP) and forward-masking subtraction ECAP (FM-ECAP), as well as the EABR waves under “normal” and “abnormal” FSANs, were obtained.

Results

Both the AP-ECAP and FM-ECAP thresholds were significantly higher than those measured by EABR under both “normal” FSAN and “abnormal” FSANs (p < 0.05). There was a significant difference in the slope values between electrodes 1 and 2 and electrodes 3 and 4 in terms of the AP-ECAP under the “abnormal” FSAN (p < 0.05). The threshold gaps between the AP-ECAP and FM-ECAP were significantly larger under the “abnormal” FSAN than under the “normal” FSAN (p < 0.05).

Conclusions

Both of the ECAP thresholds were higher than the EABR thresholds. The AP-ECAP was more sensitive than the FM-ECAP under the “abnormal” FSAN.
Evaluating prevalence of depression, anxiety and hopelessness in patients with Vitiligo on an Iranian population
Authors: Hamidizadeh Nasrin , Ranjbar Sara , Ghanizadeh Ahmad , Parvizi Mohammad Mahdi , Jafari Peyman , Handjani Farhad
Published: February 2020

Introduction

Vitiligo is caused by partial or complete destruction of melanocytes in the affected skin area and influences the patient’s quality of life. Besides physical involvement, vitiligo patients experience a high level of stress. Depression and Anxiety are common psychiatric disorders in vitiligo patients.

Aim

This study, as the first study, evaluates hopelessness, anxiety, depression and general health of vitiligo patients in comparison with normal controls in an Iranian population.

Method

Hundred patients with vitiligo and hundred healthy controls were examined. General health, depression, hopelessness and anxiety were evaluated based on general health questionnaire. Anxiety, depression and hopelessness levels were analyzed using Chi–Square, and the mean value of general health was evaluated through t-test.

Results

The results showed that anxiety and hopelessness levels were significantly higher in vitiligo patients than those who are in healthy controls. This significant difference refers to high levels of anxiety and hopelessness among women with vitiligo.

It was also found that the single patients were more anxious, hopeless and depressive, while the married patients were only more anxious and hopeless than those who are in the control group, respectively.

General health of patients was significantly worse than in healthy controls. The low level of general health in patients was related to poorer level of general health among women with vitiligo.

Conclusion

It seems that women with vitiligo are more mentally stressed than men with vitiligo. Both singles and married vitiligo patients suffer from anxiety and hopelessness.
Regeneration of skin appendages and nerves: current status and further challenges
Authors: Weng Tingting , Wu Pan , Zhang Wei , Zheng Yurong , Li Qiong , Jin Ronghua , Chen Haojiao , You Chuangang , Guo Songxue , Han Chunmao , Wang Xingang
Published: February 2020

Tissue-engineered skin (TES), as an analogue of native skin, is promising for wound repair and regeneration. However, a major drawback of TES products is a lack of skin appendages and nerves to enhance skin healing, structural integrity and skin vitality. Skin appendages and nerves are important constituents for fully functional skin. To date, many studies have yielded remarkable results in the field of skin appendages reconstruction and nerve regeneration. However, patients often complain about a loss of skin sensation and even cutaneous chronic pain. Restoration of pain, temperature, and touch perceptions should now be a major challenge to solve in order to improve patients’ quality of life. Current strategies to create skin appendages and sensory nerve regeneration are mainly based on different types of seeding cells, scaffold materials, bioactive factors and involved signaling pathways. This article provides a comprehensive overview of different strategies for, and advances in, skin appendages and sensory nerve regeneration, which is an important issue in the field of tissue engineering and regenerative medicine.
Predictors of mental distress among undergraduate health science students of Hawassa University, College of Medicine and Health Sciences, Hawassa, SNNPR, Ethiopia: a cross-sectional study
Authors: Bedaso Asres , Duko Bereket , Yeneabat Tebikew
Published: February 2020

Introduction

Mental distress is a mental health problem which includes anxiety, depression and somatic symptoms. Mental health problems affect society as a whole and no group is immune to mental disorders; however, students have significantly high level of mental distress than their community peers.

Objective

The aim of the study is to assess magnitude of mental distress and its predictors among undergraduate health science students of Hawassa University, College of Medicine and Health Sciences, SNNPR, Ethiopia.

Methods

Institution-based cross-sectional study was conducted among 311 students. Simple random sampling technique was used to select the study participants. Data were collected using pre-tested and structured self-administered questionnaire. Mental distress among students was assessed using SRQ-20, which is validated in Ethiopia. Bivariate and multivariate logistic regression model was fitted to identify predictors of mental distress among students. An adjusted odds ratio with 95% confidence interval was computed to determine the level of significance with P-value less than 0.05.

Result

A total of 309 study participants were interviewed with a response rate of 99.34%. Among the total respondents 105 (34%) of them were found to have mental distress. In multiple logistic regression analysis, poor social support (AOR = 5.28; 95% CI (2.176–12.84) and current substances use (AOR = 12.83, 95% CI (7.13–23.13), were significant predictors of mental distress among respondents.

Conclusion and recommendations

The overall magnitude of mental distress among students was found to be high. Therefore, it is recommended that mental distress needs due attention and remedial action from policy-makers, college officials, non-governmental organizations, parents, students and other concerned bodies.
Applications of patient-derived tumor xenograft models and tumor organoids
Authors: Yoshida Go J.
Published: February 2020

Patient-derived tumor xenografts (PDXs), in which tumor fragments surgically dissected from cancer patients are directly transplanted into immunodeficient mice, have emerged as a useful model for translational research aimed at facilitating precision medicine. PDX susceptibility to anti-cancer drugs is closely correlated with clinical data in patients, from whom PDX models have been derived. Accumulating evidence suggests that PDX models are highly effective in predicting the efficacy of both conventional and novel anti-cancer therapeutics. This also allows “co-clinical trials,” in which pre-clinical investigations in vivo and clinical trials could be performed in parallel or sequentially to assess drug efficacy in patients and PDXs. However, tumor heterogeneity present in PDX models and in the original tumor samples constitutes an obstacle for application of PDX models. Moreover, human stromal cells originally present in tumors dissected from patients are gradually replaced by host stromal cells as the xenograft grows. This replacement by murine stroma could preclude analysis of human tumor-stroma interactions, as some mouse stromal cytokines might not affect human carcinoma cells in PDX models. The present review highlights the biological and clinical significance of PDX models and three-dimensional patient-derived tumor organoid cultures of several kinds of solid tumors, such as those of the colon, pancreas, brain, breast, lung, skin, and ovary.
The interplay between HIF-1α and noncoding RNAs in cancer
Authors: Peng Xiafeng , Gao Han , Xu Rui , Wang Huiyu , Mei Jie , Liu Chaoying
Published: February 2020

Hypoxia is a classic characteristic of the tumor microenvironment with a significant impact on cancer progression and therapeutic response. Hypoxia-inducible factor-1 alpha (HIF-1α), the most important transcriptional regulator in the response to hypoxia, has been demonstrated to significantly modulate hypoxic gene expression and signaling transduction networks. In past few decades, growing numbers of studies have revealed the importance of noncoding RNAs (ncRNAs) in hypoxic tumor regions. These hypoxia-responsive ncRNAs (HRNs) play pivotal roles in regulating hypoxic gene expression at the transcriptional, posttranscriptional, translational and posttranslational levels. In addition, as a significant gene expression regulator, ncRNAs exhibit promising roles in regulating HIF-1α expression at multiple levels. In this review, we briefly elucidate the reciprocal regulation between HIF-1α and ncRNAs, as well as their effect on cancer cell behaviors. We also try to summarize the complex feedback loop existing between these two components. Moreover, we evaluated the biomarker potential of HRNs for the diagnosis and prognosis of cancer, as well as the potential clinical utility of shared regulatory mechanisms between HIF-1α and ncRNAs in cancer treatment, providing novel insights into tumorigenicity, which may lead to innovative clinical applications.
Decreased ovarian function and autophagy gene methylation in aging rats
Authors: Li Qiuyuan , Cai Minghui , Wang Jiao , Gao Qiang , Guo Xiaocheng , Jia Xiaotong , Xu Shanshan , Zhu Hui
Published: February 2020

Background

Degeneration of ovarian function is an obvious feature of female aging. In addition, studies have shown that autophagy decreases with age, and DNA methylation is a hallmark epigenetic pattern during aging. However, it is not clear whether the expression and DNA methylation of autophagy genes are involved in the declines in ovarian function that occur during aging.

Results

Three groups of rats were used: 6-month-old (6 M) rats, 12-month-old (12 M) rats and 24-month-old (24 M) rats. Serum E2 levels and the mRNA and protein expression levels of Atg5, Atg12, Atg16L, Beclin1 and Lc3B were significantly decreased in aged rats. In addition, the methylation levels of the Atg5 gene were significantly increased in aged rats. The expression of the Dnmt1 and Dnmt2 genes decreased with aging; however, the expression of the Dnmt3A and Dnmt3B genes gradually increased with aging.

Conclusions

Decreased autophagic activity was involved in the declines in ovarian function in aging rats. Upregulation of the DNA methyltransferases Dnmt3A and Dnmt3B may have led to methylation of the autophagy genes Atg5 and Lc3B to ultimately cause the observed decreases in autophagic activity.
Effectiveness of a new sensorized videolaryngoscope for retraining on neonatal intubation in simulation environment
Authors: Covelli Alice , Bardelli Serena , Scaramuzzo Rosa T. , Sigali Emilio , Ciantelli Massimiliano , Del Pistoia Marta , Longo Alessia , Tognarelli Selene , Menciassi Arianna , Cuttano Armando
Published: February 2020

Background

In recent years, medical training has significantly increased the use of simulation for teaching and evaluation. The retraining of medical personnel in Italy is entrusted to the program of Continuous Education in Medicine, mainly based on theoretical training. The aim of this study is to assess whether the use of a new sensorized platform for the execution of the neonatal intubation procedure in simulation environment can complement theoretical retraining of experienced health professionals.

Methods

Neonatal intubation tests were performed using a commercial manikin and a modified video-laryngoscope by the addition of force and position sensors, which provide the user with feedback when the threshold is exceeded. Two categories carried out the simulation tests: anesthesiologists and pediatricians. The categories were divided into three groups each, and various configurations were tested: the first group of both specialists carried out the tests without feedback (i.e. control groups, gr. A and A1), the second groups received sound and visual feedback from the instrument (gr. B and B1) and the third ones had also the support of a physician expert in the use of the instrument (gr. C and C1). The instrumentation used by pediatricians was provided in a playful form, including a game with increasing difficulty levels.

Results

Both in the case with feedback only and in the case with humans support, anesthesiologists did not show a specific trend of improvement. Pediatricians, in comparison with anesthesiologists, showed a positive reaction to both the presence of feedback and that of experienced personnel. Comparing the performance of the two control groups, the two categories of experienced doctors perform similar forces. Pediatricians enjoyed the “Level Game”, through which they were able to test and confront themselves, trying to improve their own performance.

Conclusions

Our instrument is more effective when is playful and competitive, introducing something more than just a sound feedback, and allowing training by increasing levels. It is more effective if the users can adapt their own technique to the instrument by themselves, without any external help.
ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis
Authors: Zundelevich Adi , Dadiani Maya , Kahana-Edwin Smadar , Itay Amit , Sella Tal , Gadot Moran , Cesarkas Karen , Farage-Barhom Sarit , Saar Efrat Glick , Eyal Eran , Kol Nitzan , Pavlovski Anya , Balint-Lahat Nora , Dick-Necula Daniela , Barshack Iris , Kaufman Bella , Gal-Yam Einav Nili
Published: February 2020

Background

Emerging mutations in the ESR1 gene that encodes for the estrogen receptor (ER) are associated with resistance to endocrine therapy. ESR1 mutations rarely exist in primary tumors (~ 1%) but are relatively common (10–50%) in metastatic, endocrine therapy-resistant cancers and are associated with a shorter progression-free survival. Little is known about the incidence and clinical implication of these mutations in early recurrence events, such as local recurrences or newly diagnosed metastatic disease.

Methods

We collected 130 archival tumor samples from 103 breast cancer patients treated with endocrine therapy prior to their local/metastatic recurrence. The cohort consisted of 41 patients having at least 1 sample from local/loco-regional recurrence and 62 patients with metastatic disease (of whom 41 newly diagnosed and 28 with advanced disease). The 5 most common ESR1 hotspot mutations (D538G, L536R, Y537S/N/C) were analyzed either by targeted sequencing or by droplet digital PCR. Progression-free survival (PFS), disease-free survival (DFS), and distant recurrence-free survival (DRFS) were statistically tested by Kaplan-Meier analysis.

Results

The prevalence of ESR1 mutations was 5/41 (12%) in newly diagnosed metastatic patients and 5/28 (18%) for advanced metastases, detected at allele frequency > 1%. All mutations in advanced metastases were detected in patients previously treated with both tamoxifen (TAM) and aromatase inhibitors (AI). However, in newly diagnosed metastatic patients, 4/5 mutations occurred in patients treated with TAM alone. PFS on AI treatment in metastatic patients was significantly shorter for ESR1 mutation carriers (p = 0.017). In the local recurrence cohort, ESR1 mutations were identified in 15/41 (36%) patients but only 4/41 (10%) were detected at allele frequency > 1%. Again, most mutations (3/4) were detected under TAM monotherapy. Notably, 1 patient developed ESR1 mutation while on neoadjuvant endocrine therapy. DFS and DRFS were significantly shorter (p = 0.04 and p = 0.017, respectively) in patients that had ESR1 mutations (> 1%) in their loco-regional recurrence tumor.

Conclusions

Clinically relevant ESR1 mutations are prevalent in newly diagnosed metastatic and local recurrence of endocrine-treated breast cancer. Since local recurrences are amenable to curative therapy, these mutations may inform the selection of subsequent endocrine therapies.
scAI: an unsupervised approach for the integrative analysis of parallel single-cell transcriptomic and epigenomic profiles
Authors: Jin Suoqin , Zhang Lihua , Nie Qing
Published: February 2020

Simultaneous measurements of transcriptomic and epigenomic profiles in the same individual cells provide an unprecedented opportunity to understand cell fates. However, effective approaches for the integrative analysis of such data are lacking. Here, we present a single-cell aggregation and integration (scAI) method to deconvolute cellular heterogeneity from parallel transcriptomic and epigenomic profiles. Through iterative learning, scAI aggregates sparse epigenomic signals in similar cells learned in an unsupervised manner, allowing coherent fusion with transcriptomic measurements. Simulation studies and applications to three real datasets demonstrate its capability of dissecting cellular heterogeneity within both transcriptomic and epigenomic layers and understanding transcriptional regulatory mechanisms.
Bioconversion of ferulic acid attained from pineapple peels and pineapple crown leaves into vanillic acid and vanillin by Aspergillus niger I-1472
Authors: Tang Pei Ling , Hassan Osman
Published: February 2020

This study was conducted to evaluate the potential of pineapple peel (PP) and pineapple crown leaves (PCL) as the substrate for vanillic acid and vanillin production. About 202 ± 18 mg L−1 and 120 ± 11 mg L−1 of ferulic acid was produced from the PP and PCL respectively. By applied response surface methodology, the ferulic acid yield was increased to 1055 ± 160 mg L−1 by treating 19.3% of PP for 76 min, and 328 ± 23 mg L−1 by treating 9.9% of PCL for 36 min in aqueous sodium hydroxide solution at 120 °C. The results revealed that PP extract was better than PCL extract for vanillic acid and vanillin production. Furthermore, the experiment also proved that large volume feeding was more efficient than small volume feeding for high vanillic acid and vanillin yield. Through large volume feeding, about 7 ± 2 mg L−1 of vanillic acid and 5 ± 1 mg L−1 of vanillin was successfully produced from PP extract via Aspergillus niger fermentation.
Health coaching for promoting physical activity in low back pain patients: a secondary analysis on the usage and acceptance
Authors: Dejonghe Lea Anna Lisa , Rudolf Kevin , Becker Jennifer , Stassen Gerrit , Froboese Ingo , Schaller Andrea
Published: February 2020

Background

Multicomponent interventions combined with health coaching are widely recommended to improve a healthy lifestyle. The aim of the present study was to analyse the usage and acceptance of a multicomponent intervention (telephone, web and face-to-face coaching) for low back pain patients, and thereby gain an understanding of why this intervention was not as effective as expected.

Methods

A secondary analysis of a randomised controlled trial, aimed at promoting physical activity, was conducted. It was a cross-sectional study based on data of a multicomponent intervention group (baseline = 201 participants). For evaluating the usage and acceptance, descriptive statistics were applied.

Results

Over half (n = 118) of the patients participated at least once in the telephone coaching. Approximately half of the participants (44 of 90) rated the telephone coaching as “good”.

34 of 92 (37%) participants reported of visiting the web-platform. The web-platform was comprehensible for nearly one-quarter (n = 8 of 33) and very useful for one participant.

The face-to-face-contact was rated highly (range: 79.4–88.2 out of 100).

Conclusion

Usage of the telephone coaching approach was moderate with even fewer participants visiting the web-platform. In addition, these approaches were not rated as very useful. The acceptance of the face-to-face contact was high.

Since the usage and acceptance could influence the effectiveness, utilisation and acceptance studies might help to explain the reason for non-effective lifestyle interventions. Therefore, more studies analysing the usage and acceptance are needed. To improve the usage and acceptance, a stronger participatory orientation in the design of interventions and the integration of face-to-face contact could be helpful.
AICAR and nicotinamide treatment synergistically augment the proliferation and attenuate senescence-associated changes in mesenchymal stromal cells
Authors: Khorraminejad-Shirazi Mohammadhossein , Sani Mahsa , Talaei-Khozani Tahereh , Dorvash Mohammadreza , Mirzaei Malihe , Faghihi Mohammad Ali , Monabati Ahmad , Attar Armin
Published: February 2020

Background

Mesenchymal stromal cell (MSC) stemness capacity diminishes over prolonged in vitro culture, which negatively affects their application in regenerative medicine. To slow down the senescence of MSCs, here, we have evaluated the in vitro effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMPK activator, and nicotinamide (NAM), an activator of sirtuin1 (SIRT1).

Methods

Human adipose-derived MSCs were cultured to passage (P) 5. Subsequently, the cells were grown in either normal medium alone (control group), the medium supplemented with AICAR (1 mM) and NAM (5 mM), or in the presence of both for 5 weeks to P10. Cell proliferation, differentiation capacity, level of apoptosis and autophagy, morphological changes, total cellular reactive oxygen species (ROS), and activity of mTORC1 and AMPK were compared among different treatment groups.

Results

MSCs treated with AICAR, NAM, or both displayed an increase in proliferation and osteogenic differentiation, which was augmented in the group receiving both. Treatment with AICAR or NAM led to decreased expression of β-galactosidase, reduced accumulation of dysfunctional lysosomes, and characteristic morphologic features of young MSCs. Furthermore, while NAM administration could significantly reduce the total cellular ROS in aged MSCs, AICAR treatment did not. Moreover, AICAR-treated cells possess a high proliferation capacity; however, they also show the highest level of cellular apoptosis. The observed effects of AICAR and NAM were in light of the attenuated mTORC1 activity and increased AMPK activity and autophagy.

Conclusions

Selective inhibition of mTORC1 by AICAR and NAM boosts autophagy, retains MSCs’ self-renewal and multi-lineage differentiation capacity, and postpones senescence-associated changes after prolonged in vitro culture. Additionally, co-administration of AICAR and NAM shows an additive or probably a synergistic effect on cellular senescence.
Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions
Authors: Ortiz-Hernandez Greisha L. , Sanchez-Hernandez Evelyn S. , Casiano Carlos A.
Published: February 2020

The discovery and initial characterization 20 years ago of antinuclear autoantibodies (ANAs) presenting a dense fine speckled (DFS) nuclear pattern with strong staining of mitotic chromosomes, detected by indirect immunofluorescence assay in HEp-2 cells (HEp-2 IIFA test), has transformed our view on ANAs. Traditionally, ANAs have been considered as reporters of abnormal immunological events associated with the onset and progression of systemic autoimmune rheumatic diseases (SARD), also called ANA-associated rheumatic diseases (AARD), as well as clinical biomarkers for the differential diagnosis of these diseases. However, based on our current knowledge, it is not apparent that autoantibodies presenting the DFS IIF pattern fall into these categories. These antibodies invariably target a chromatin-associated protein designated as dense fine speckled protein of 70 kD (DFS70), also known as lens epithelium-derived growth factor protein of 75 kD (LEDGF/p75) and PC4 and SFRS1 Interacting protein 1 (PSIP1). This multi-functional protein, hereafter referred to as DFS70/LEDGF, plays important roles in the formation of transcription complexes in active chromatin, transcriptional activation of specific genes, regulation of mRNA splicing, DNA repair, and cellular survival against stress. Due to its multiple functions, it has emerged as a key protein contributing to several human pathologies, including acquired immunodeficiency syndrome (AIDS), leukemia, cancer, ocular diseases, and Rett syndrome. Unlike other ANAs, “monospecific” anti-DFS70/LEDGF autoantibodies (only detectable ANA in serum) are not associated with SARD and have been detected in healthy individuals and some patients with non-SARD inflammatory conditions. These observations have led to the hypotheses that these antibodies could be considered as negative biomarkers of SARD and might even play a protective or beneficial role. In spite of 20 years of research on this autoantibody-autoantigen system, its biological and clinical significance still remains enigmatic. Here we review the current state of knowledge of this system, focusing on the lessons learned and posing emerging questions that await further scrutiny as we continue our quest to unravel its significance and potential clinical and therapeutic utility.