bluuebunny/crossref_metadata_2025 huggingface dataset:
The MDM2 ligand Nutlin-3 differentially alters expression of the immune blockade receptors PD-L1 and CD276
Authors: Li Ruidong , Zatloukalova Pavlina , Muller Petr , Gil-Mir Maria , Kote Sachin , Wilkinson Simon , Kemp Alain J. , Hernychova Lenka , Wang Yaxin , Ball Kathryn L. , Tao Kaixiong , Hupp Ted , Vojtesek Borivoj
Published: August 2020

Background

The links between the p53/MDM2 pathway and the expression of pro-oncogenic immune inhibitory receptors in tumor cells are undefined. In this report, we evaluate whether there is p53 and/or MDM2 dependence in the expression of two key immune receptors, CD276 and PD-L1.

Methods

Proximity ligation assays were used to quantify protein-protein interactions in situ in response to Nutlin-3. A panel of p53-null melanoma cells was created using CRISPR-Cas9 guide RNA mediated genetic ablation. Flow cytometric analyses were used to assess the impact of TP53 or ATG5 gene ablation, as well as the effects of Nutlin-3 and an ATM inhibitor on cell surface PD-L1 and CD276. Targeted siRNA was used to deplete CD276 to assess changes in cell cycle parameters by flow cytometry. A T-cell proliferation assay was used to assess activity of CD4+ T-cells as a function of ATG5 genotype.

Results

CD276 forms protein-protein interactions with MDM2 in response to Nutlin-3, similar to the known MDM2 interactors p53 and HSP70. Isogenic HCT116 p53-wt/null cancer cells demonstrated that CD276 is induced on the cell surface by Nutlin-3 in a p53-dependent manner. PD-L1 was also unexpectedly induced by Nutlin-3, but PD-L1 does not bind MDM2. The ATM inhibitor KU55993 reduced the levels of PD-L1 under conditions where Nutlin-3 induces PD-L1, indicating that MDM2 and ATM have opposing effects on PD-L1 steady-state levels. PD-L1 is also up-regulated in response to genetic ablation of TP53 in A375 melanoma cell clones under conditions in which CD276 remains unaffected. A549 cells with a deletion in the ATG5 gene up-regulated only PD-L1, further indicating that PD-L1 and CD276 are under distinct genetic control.

Conclusion

Genetic inactivation of TP53, or the use of the MDM2 ligand Nutlin-3, alters the expression of the immune blockade receptors PD-L1 and CD276. The biological function of elevated CD276 is to promote altered cell cycle progression in response to Nutlin-3, whilst the major effect of elevated PD-L1 is T-cell suppression. These data indicate that TP53 gene status, ATM and MDM2 influence PD-L1 and CD276 paralogs on the cell surface. These data have implications for the use of drugs that target the p53 pathway as modifiers of immune checkpoint receptor expression.
Testosterone deficiency caused by castration increases adiposity in male rats in a tissue-specific and diet-dependent manner
Authors: Baik Myunggi , Jeong Jin Young , Park Seung Ju , Yoo Seon Pil , Lee Jin Oh. , Lee Jae Sung , Haque Md Najmul , Lee Hyun-Jeong
Published: August 2020

Background

Testosterone deficiency in men is clinically associated with the development of metabolic syndrome, which manifests as obesity, hepatic steatosis, and type-2 diabetes. We investigated the effects of castration-induced testosterone deficiency on body adiposity and the expression of genes related to lipid metabolism and glucose uptake and androgen signaling in male rats fed a normal diet (ND) or a high-fat diet (HFD).

Methods

Changes in lipid and glucose metabolism and androgen signaling were investigated at physiological and molecular levels in the muscle, liver, and adipose tissues of non-castrated and castrated rats under ND or HFD feeding.

Results

Castration-induced testosterone deficiency predisposed animals on ND to early development of fatty liver by activating fatty acid (FA) synthesis, whereas HFD activated hepatic FA uptake CD36 expression, leading to the development of hepatic steatosis. In rats fed ND, castration induced muscle fat accumulation by activating CD36 expression. In the subcutaneous fat of ND-fed rats, castration increased adiposity and the expression of FA synthesis-related genes, but it decreased glucose transporter gene expression. In the abdominal fat of rats fed ND, castration increased adiposity by upregulating FA synthesis-related genes, and HFD promoted adiposity by inducing FA uptake, glucose transporter, and FA synthesis-related gene expression. In rats fed ND, castration decreased body growth and muscle weight and downregulated the expression of genes androgen signaling in the longissimus dorsi muscle.

Conclusions

Testosterone deficiency increases adiposity in a tissue-specific and diet-dependent manner. Testosterone deficiency decreases body and muscle weights and downregulates androgen signaling.
Joint pre-processing framework for two-dimensional gel electrophoresis images based on nonlinear filtering, background correction and normalization techniques
Authors: Goez Manuel Mauricio , Torres-Madronero Maria C. , Rothlisberger Sarah , Delgado-Trejos Edilson
Published: August 2020

Background

Two-dimensional gel electrophoresis (2-DGE) is a commonly used tool for proteomic analysis. This gel-based technique separates proteins in a sample according to their isoelectric point and molecular weight. 2-DGE images often present anomalies due to the acquisition process, such as: diffuse and overlapping spots, and background noise. This study proposes a joint pre-processing framework that combines the capabilities of nonlinear filtering, background correction and image normalization techniques for pre-processing 2-DGE images. Among the most important, joint nonlinear diffusion filtering, adaptive piecewise histogram equalization and multilevel thresholding were evaluated using both synthetic data and real 2-DGE images.

Results

An improvement of up to 46% in spot detection efficiency was achieved for synthetic data using the proposed framework compared to implementing a single technique of either normalization, background correction or filtering. Additionally, the proposed framework increased the detection of low abundance spots by 20% for synthetic data compared to a normalization technique, and increased the background estimation by 67% compared to a background correction technique. In terms of real data, the joint pre-processing framework reduced the false positives up to 93%.

Conclusions

The proposed joint pre-processing framework outperforms results achieved with a single approach. The best structure was obtained with the ordered combination of adaptive piecewise histogram equalization for image normalization, geometric nonlinear diffusion (GNDF) for filtering, and multilevel thresholding for background correction.
Predicting the most deleterious missense nsSNPs of the protein isoforms of the human HLA-G gene and in silico evaluation of their structural and functional consequences
Authors: Emadi Elaheh , Akhoundi Fatemeh , Kalantar Seyed Mehdi , Emadi-Baygi Modjtaba
Published: August 2020

Background

The Human Leukocyte Antigen G (HLA-G) protein is an immune tolerogenic molecule with 7 isoforms. The change of expression level and some polymorphisms of the HLA-G gene are involved in various pathologies. Therefore, this study aimed to predict the most deleterious missense non-synonymous single nucleotide polymorphisms (nsSNPs) in HLA-G isoforms via in silico analyses and to examine structural and functional effects of the predicted nsSNPs on HLA-G isoforms.

Results

Out of 301 reported SNPs in dbSNP, 35 missense SNPs in isoform 1, 35 missense SNPs in isoform 5, 8 missense SNPs in all membrane-bound HLA-G isoforms and 8 missense SNPs in all soluble HLA-G isoforms were predicted as deleterious by all eight servers (SIFT, PROVEAN, PolyPhen-2, I-Mutant 3.0, SNPs&GO, PhD-SNP, SNAP2, and MUpro). The Structural and functional effects of the predicted nsSNPs on HLA-G isoforms were determined by MutPred2 and HOPE servers, respectively. Consurf analyses showed that the majority of the predicted nsSNPs occur in conserved sites. I-TASSER and Chimera were used for modeling of the predicted nsSNPs. rs182801644 and rs771111444 were related to creating functional patterns in 5′UTR. 5 SNPs in 3′UTR of the HLA-G gene were predicted to affect the miRNA target sites. Kaplan-Meier analysis showed the HLA-G deregulation can serve as a prognostic marker for some cancers.

Conclusions

The implementation of in silico SNP prioritization methods provides a great framework for the recognition of functional SNPs. The results obtained from the current study would be called laboratory investigations.
Comparative genomic analysis of a Shiga toxin-producing Escherichia coli (STEC) O145:H25 associated with a severe pediatric case of hemolytic uremic syndrome in Davidson County, Tennessee, US
Authors: Guerra Julio A. , Zhang Chengxian , Bard Jonathan E. , Yergeau Donald , Halasa Natasha , Gómez-Duarte Oscar G.
Published: August 2020

Background

Shiga toxin-producing E. coli (STECs) are foodborne pathogens associated with bloody diarrhea and hemolytic uremic syndrome (HUS). Although the STEC O157 serogroup accounts for the highest number of infections, HUS-related complications and deaths, the STEC non-O157, as a group, accounts for a larger proportion of STEC infections and lower HUS cases. There is limited information available on how to recognize non-O157 serotypes associated with severe disease. The objectives of this study were to describe a patient with STEC non-O157 infection complicated with HUS and to conduct a comparative whole genome sequence (WGS) analysis among the patient’s STEC clinical isolate and STEC O157 and non-O157 strains.

Results

The STEC O145:H25 strain EN1I-0044-2 was isolated from a pediatric patient with diarrhea, HUS and severe neurologic and cardiorespiratory complications, who was enrolled in a previously reported case-control study of acute gastroenteritis conducted in Davidson County, Tennessee in 2013. The strain EN1I-0044-2 genome sequence contained a chromosome and three plasmids. Two of the plasmids were similar to those present in O145:H25 strains whereas the third unique plasmid EN1I-0044-2_03 shared no similarity with other STEC plasmids, and it carried 23 genes of unknown function. Strain EN1I-0044-2, compared with O145:H25 and O157 serogroup strains shared chromosome- and plasmid-encoded virulence factors, including Shiga toxin, LEE type III secretion system, LEE effectors, SFP fimbriae, and additional toxins and colonization factors.

Conclusions

A STEC O145:H25 strain EN1I-0044-2 was isolated from a pediatric patient with severe disease, including HUS, in Davidson County, TN. Phylogenetic and comparison WGS analysis provided evidence that strain EN1I-0044-2 closely resembles O145:H25, and confirmed an independent evolutionary path of STEC O145:H25 and O145:H28 serotypes. The strain EN1I-0044-2 virulence make up was similar to other O145:H25 and O157 serogroups. It carried stx2 and the LEE pathogenicity island, and additional colonization factors and enterotoxin genes. A unique feature of strain EN1I-0044-2 was the presence of plasmid pEN1I-0044-2_03 carrying genes with functions to be determined. Further studies will be necessary to elucidate the role that newly acquired genes by O145:H25 strains play in pathogenesis, and to determine if they may serve as genetic markers of severe disease.
Dynamic transcriptome and metabolome analyses of two types of rice during the seed germination and young seedling growth stages
Authors: Yang Jing , Su Ling , Li Dandan , Luo Lixin , Sun Kai , Yang Meng , Gu Fengwei , Xia Aoyun , Liu Yongzhu , Wang Hui , Chen Zhiqiang , Guo Tao
Published: August 2020

Background

Seed germination and young seedling growth are important agricultural traits for developing populations of both irrigated and directly seeded rice. Previous studies have focused on the identification of QTLs. However, there are few studies on the metabolome or transcriptome of germination and young seedling growth in rice.

Results

Here, an indica rice and a japonica rice were used as materials, and the transcripts and metabolites were detected during the germination and young seedling growth periods on a large scale by using RNA sequencing and a widely targeted metabolomics method, respectively. Fourteen shared transcripts and 15 shared metabolites that were continuously differentially expressed in the two materials were identified and may be essential for seed germination and young seedling growth. Enrichment analysis of differentially expressed genes in transcriptome expression profiles at different stages indicated that cell wall metabolism, lipid metabolism, nucleotide degradation, amino acid, etc., were enriched at 0–2 days, and most of the results are consistent with those of previous reports. Specifically, phenylpropanoid biosynthesis and glutathione metabolism were continuously enriched during the seed germination and young seedling growth stages. Next, KO enrichment analysis was conducted by using the differentially expressed genes of the two materials at 2, 3 and 4 days. Fourteen pathways were enriched. Additionally, 44 differentially expressed metabolites at 2, 3 and 4 days were identified. These metabolites may be responsible for the differences in germination and young seedling growth between the two materials. Further attention was focused on the ascorbate–glutathione pathway, and it was found that differences in ROS-scavenging abilities mediated by some APX, GPX and GST genes may be directly involved in mediating differences in the germination and young seedling growth speed of the two materials.

Conclusions

In summary, these results may enhance the understanding of the overall mechanism of seed germination and young seedling growth, and the outcome of this study is expected to facilitate rice breeding for direct seeding.
Functional training added to intradialytic cycling lowers low-density lipoprotein cholesterol and improves dialysis adequacy: a randomized controlled trial
Authors: Bogataj Špela , Pajek Jernej , Buturović Ponikvar Jadranka , Pajek Maja
Published: August 2020

Background

Exercise has various positive effects on hemodialysis patients. However, there is no clear evidence which type of exercise yields better results. This study aimed to determine the effects of guided functional training added to the intradialytic cycling on dialysis adequacy and biochemical parameters in hemodialysis patients. Additionally, we aimed to investigate if patients could transfer functional exercise to an unsupervised home environment and retain gained improvements.

Methods

Randomization was done to a functional training intervention group (INT) (n = 20) or intradialytic cycling control group (CON) (n = 20). The INT attended a pre-dialysis functional training in the first 8 weeks. In the second 8 weeks, they performed functional exercises at unsupervised home environment on non-dialysis days. During the whole study, both groups participated in the intradialytic cycling program.

Results

Both groups demonstrated a significant increase in dialysis adequacy (Kt/V) in the eight (0.15, 95% CI 0.06 to 0.24; p = 0.003 for INT and 0.21, 95% CI 0.11 to 0.3; p < 0.001 for CON) and the 16th study week (0.13, 95% CI 0.03 to 0.24; p = 0.017 for INT and 0.13, 95% CI 0.03 to 0.22; p = 0.013 for CON) compared to their baseline values with no significant between-group differences. At week eight, the total cholesterol was significantly lowered in the INT (− 0.34 mmol/L, 95% CI − 0.6 to − 0.07; p = 0.016) and remained lower at week 16 (− 0.32 mmol/L, 95% CI − 0.64 to − 0.01; p = 0.049) with no significant changes in the CON. Low-density lipoprotein levels in the INT were significantly reduced after 8 weeks (− 0.35 mmol/L, 95% CI − 0.64 to − 0.06; p = 0.022) and remained reduced after 16 weeks (− 0.28 mmol/L, 95% CI − 0.52 to − 0.03; p = 0.030). There were no significant differences found for albumin, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, and hemoglobin in both groups.

Conclusions

We demonstrated that functional training added to intradialytic cycling improved lipid profile and dialysis adequacy. Additionally, the effects of the unsupervised, home-based program were preserved during the second study phase. This study supports the assumption that combined training is more effective compared to solely intradialytic exercise.

Trial registration

ClinicalTrials.Gov, NCT03334123. Registered 07 November 2017.
Urine concentration ability is reduced to the same degree in adult dominant polycystic kidney disease compared with other chronic kidney diseases in the same CKD-stage and lower THAN in healthy control subjects - a CASE control study
Authors: Malmberg M. H. , Mose F. H. , Pedersen E. B. , Bech J. N.
Published: August 2020

Background

Concentration of the urine is primarily regulated via vasopressin dependent aquaporin-2 water channels in the apical membrane of kidney principal cells. It is unclear whether urine concentration ability in ADPKD differs from other patients with similar degree of impaired renal function (non-ADPKD patients). The purpose of this case control study was to measure urine concentration ability in ADPKD patients compared to non-ADPKD patients and healthy controls.

Methods

A seventeen hour long water deprivation test was carried out in 17 ADPKD patients (CKD I-IV), 16 non-ADPKD patients (CKD I-IV), and 18 healthy controls. Urine was collected in 4 consecutive periods during water deprivation (12 h, 1 h, 2 h and 2 h, respectively) and analyzed for osmolality (u-Osm), output (UO), fractional excretion of sodium (FENa), aquaporin2 (u-AQP2) and ENaC (u-ENaC). Blood samples were drawn trice (after 13-, 15-, and 17 h after water deprivation) for analyses of osmolality (p-Osm), vasopressin (p-AVP), and aldosterone (p-Aldo).

Results

U-Osm was significantly lower and FENa significantly higher in both ADPKD patients and non-ADPKD patients compared to healthy controls during the last three periods of water deprivation. During the same periods, UO was higher and secretion rates of u-AQP2 and u-ENaC were lower and at the same level in the two groups of patients compared to controls. P-AVP and p-Osm did not differ significantly between the three groups. P-Aldo was higher in both groups of patients than in controls.

Conclusions

Urine concentration ability was reduced to the same extent in patients with ADPKD and other chronic kidney diseases with the same level of renal function compared to healthy controls. The lower urine excretion of AQP2 and ENaC suggests that the underlying mechanism may be a reduced tubular response to vasopressin and aldosterone.

Trial registration

Current Controlled Trial NCT04363554, date of registration: 20.08.2017.
Characteristics of cognitive impairment in adult asymptomatic moyamoya disease
Authors: He Shihao , Duan Ran , Liu Ziqi , Ye Xun , Yuan Li , Li Tian , Tan Cunxin , Shao Junshi , Qin Shusen , Wang Rong
Published: August 2020

Background

Cognitive impairment in adult moyamoya disease (MMD) is thought to be the result of ischemic stroke; however, the presence and extent of cognitive decline in asymptomatic patients is unclear.

Methods

After classification using T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), a total of 19 MMD patients with a history of cerebral infarction, 21 asymptomatic MMD patients, and 20 healthy controls matched for age, sex, and years of education were prospectively included in this study. A detailed neuropsychological evaluation of two moyamoya subgroups and normal controls was conducted.

Results

Asymptomatic patients showed varying degrees of decline in intelligence (Raven’s Standard Progressive Matrices, P = 0.001), spatial imagination (mental rotation, P = 0.014), working memory (verbal working memory-backward digit span, P = 0.011), and computational ability (simple subtraction, P = 0.014; complex subtraction, P < 0.001) compared with normal controls. MMD patients with cerebral infarction had more severe impairment in complex arithmetic (P = 0.027) and word short-term memory (P = 0.01) than those without symptoms.

Conclusion

In asymptomatic MMD patients, a variety of cognitive impairment precedes the onset of clinical symptoms such as cerebral infarction, which may be a long-term complication of conservative treatment.
Multi-measure assessment of adherence to antiretroviral therapy among children under five years living with HIV in Jinja, Uganda
Authors: Ssanyu Jacquellyn Nambi , Nakafeero Mary , Nuwaha Fred
Published: August 2020

Background

Adherence to Antiretroviral Therapy (ART) is required to achieve HIV viral load suppression. However, children under 5 years in Jinja, Uganda, had been shown to have low HIV suppression rates. This study aimed to determine the level of ART non-adherence among these children and the associated factors.

Methods

Data for the cross-sectional study was collected from April to July 2019, from caregivers of 206 children under 5 years living with HIV who were attending health facilities in Jinja and had been on ART for at least 3 months. Non-adherence was measured using a Visual Analog Scale that assessed both dosing and timing non-adherence, and by determining the Proportion of Days Covered by the medication. A questionnaire administered to the caregivers was used to collect the data, together with medical record review. A child was only considered adherent if they had adherence greater than 95% on all the measures. The data was analysed using Modified Poisson Regression, taking ap-value less than 0.05 as statistically significant.

Results

Of the 206 children, 73.8% were older than 2 years, and 52.9% were female. Likewise, the majority of caregivers were female (93.7%). Using the combined adherence measure, 57.3% of the children were categorised as non-adherent. School/day-care attendance, Prevalence Ratio (PR) = 1.25 (p = 0.042), the caregiver having higher than a primary school education, PR = 0.72 (p = 0.044) and satisfaction with the quality of service at the health facility, PR = 0.97 (p < 0.001) were associated with non-adherence. Household food insecurity was also associated with non-adherence: PR = 1.55 (p = 0.011) for mild food insecurity, PR = 1.75 (p = 0.001) for moderate insecurity and PR = 1.48 (p = 0.015) for severe food insecurity.

Conclusions

Children under 5 years in Jinja had a high level of ART non-adherence. It is important to engage schools to support adherence among children living with HIV. Addressing household food insecurity and improving the quality of paediatric ART services would also reduce the barriers to optimal adherence.
Pathogenic characteristics of sputum and bronchoalveolar lavage fluid samples from patients with lower respiratory tract infection in a large teaching hospital in China: a retrospective study
Authors: Peng Zheng , Zhou Jin’an , Tian Lei
Published: August 2020

Background

Lower respiratory tract infection (LRIs) is very common both in terms of community-acquired infection and hospital-acquired infection. Sputum and bronchoalveolar lavage fluid (BALF) are the most important specimens obtained from patients with LRI. The choice of antibiotic with which to treat LRI usually depends on the antimicrobial sensitivity of bacteria isolated from sputum and BALF. However, differences in the antimicrobial sensitivity of pathogens isolated from sputum and BALF have not been evaluated.

Methods

A retrospective study was conducted to analyze the differences between sputum and BALF samples in terms of pathogen isolation and antimicrobial sensitivity in hospitalized patients with LRI.

Results

Between 2013 and 2015, quality evaluation of sputum samples was not conducted before performing sputum culture; however, between 2016 and 2018, quality evaluation of sputum samples was conducted first, and only quality-assured samples were cultured. The numbers of sputum and BALF in 2013–2015 were 15,549 and 1671, while those in 2016–2018 were 12,055 and 3735, respectively. The results of pathogen culture showed that Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Hemophilus influenzae, Escherichia coli, Stenotrophomonas maltophilia, and Streptococcus pneumoniae were in the top ten pathogens isolated from sputum and BALF. An antimicrobial susceptibility test showed that the susceptibility of BALF isolates to most antibiotics was higher compared with the susceptibility of sputum isolates, especially after quality control of sputum samples (2016–2018).

Conclusions

Our findings suggest that caution is needed in making therapeutic choices for patients with LRI when using antimicrobial sensitivity results from sputum isolates as opposed to BALF isolates.
Lateral Unicompartmental knee arthroplasty for a secondary osteonecrosis of the lateral femoral condyle. A case report
Authors: Yang Tao , Xue Huaming , Ma Tong , Wen Tao , Xue Long , Guan Mengyin , Tu Yihui
Published: August 2020

Background

Secondary osteonecrosis of the knee is a rare event. There are few reports regarding management of this condition. The aim of the present study is to report treatment outcomes for secondary osteonecrosis of the lateral condyle treated with unicompartmental knee arthroplasty (UKA).

Case presentation

A 54-year-old woman with idiopathic thrombocytopenic purpura, who received low-dosage corticosteroids, complained of knee pain for 5 years and difficulty walking in the last 5 months. Fixed-bearing lateral UKA was performed under general anesthesia combined with midthigh saphenous nerve block. The patient could walk without ambulation aid shortly after the operation and achieved satisfactory knee joint function at the 6-week follow-up. The knee society score (KSS) increased from 68 to 91. The follow-up period was up to 1 year. There was no pain, loosening, or fracture of the prosthesis at the latest follow-up.

Conclusions

This case study demonstrates successful management of secondary osteonecrosis of the lateral femoral condyle is possible with a fixed bearing lateral UKA. Early diagnosis, rigorous indication, and appropriate surgical techniques were critical to maximizing prosthesis stability in lateral UKA.
A new method for assessment of nickel-titanium endodontic instrument surface roughness using field emission scanning electronic microscope
Authors: Van Pham Khoa , Vo Canh Quang
Published: August 2020

Background

To introduce a new method for measurement of surface roughness of the endodontic instrument, before and after instrumentation, using the Field Emission Scanning Electronic Microscope (FE-SEM) combined with the ImageJ software.

Methods

Twenty J-shape resin blocks were divided into two groups, ten blocks of each group. Simulated root canal inside the resin block was 16 mm length, 600angle of curvature, and radius of 4.5 mm. Ten WaveOne Gold Primary and 10 Reciproc Blue R25 instruments were used for root canal instrumentation. The instruments were scanned before and after instrumentation with special molds made to ensure the same areas at the point located 3 mm from the tips of the instruments using the FE-SEM. These scanned images were analyzed using the ImageJ. The arithmetical mean roughness (Ra), root mean square roughness (Rq), and the average distance between the highest peak and lowest valley in each sampling length (Rz) were calculated by ImageJ for quantitative analyses. The paired-t test was performed to analyze the data using the SPSS 22.0 at the significance of .05.

Results

Almost all surface roughness values were decreased. However, these decreases were not statistically significant (P > .05).

Conclusions

The FE-SEM combined with the ImageJ was the reliable and appropriate modality for measurement surface roughness of instruments.
Prevalence of high-risk behaviors in reproductive age women in Alborz province in 2019 using unmatched count technique
Authors: Bahadivand Samira , Doosti-Irani Amin , Karami Manoochehr , Qorbani Mostafa , Mohammadi Younes
Published: August 2020

Background

Our knowledge on the prevalence of high-risk behaviors among women of Alborz is not reliable due to the sensitivity of the issue. This study aimed to estimate the prevalence of seven risk behaviors among the reproductive age women in Alborz Province, Iran.

Method

In this cross-sectional study, 2000 women were randomly selected from a registered healthcare system in 2019. A researcher-made questionnaire was used to collect the required data. The prevalence of the risk behaviors including drug abuse, hookah, alcohol drinking, tobacco smoking, extramarital intercourse, and gambling was estimated using the unmatched count technique, and the prevalence rate was reported at a 95% confidence interval.

Results

The response rate for this study was 95%. The estimated prevalence for drug abuse, hookah, alcohol drinking, tobacco smoking, extramarital intercourse, and gambling were 3% (95%CI: 2.78 to 3.22), 10.5% (95%CI: 10.29 to 10.71), 7% (95%CI: 6.78 to 7.22), 10% (95%CI: 9.78 to 10.22), 8.7% (95%CI, 8.29 to 8.71), and 7.5% (95%CI, 4.71 to 7.28), respectively.

Conclusion

High risk behaviors are highly prevalent among Iranian women. Enforcing laws, prohibition, marketing restrictions, increasing taxation, expanding treatment, promoting condom distribution and providing community-based service are recommended to reduce the effects of high risk behaviors among women.
Continuing nursing education: use of observational pain assessment tool for diagnosis and management of pain in critically ill patients following training through a social networking app versus lectures
Authors: Deldar Kolsoum , Froutan Razieh , Sedaghat Alireza , Mazlom Seyed Reza
Published: August 2020

Background

Nursing staff training in using observational pain assessment tools is highly important to improve the assessment of pain. The present study was conducted to examine the effect of two different training methods (lectures vs. a social networking app) on the diagnosis and management of pain in mechanically-ventilated patients.

Methods

This quasi-experimental study was conducted on 70 nurses working in two Intensive Care Units (ICU) in Mashhad, Iran. The nurses were trained in the application of observational pain assessment tools by lectures or through a social networking app. Before and after the intervention, the nurses’ performance was evaluated in both groups using a checklist based on Critical-Care Pain Observation Tool (CPOT).

Results

In the pre-intervention phase, the nurses’ performance scores in the domains of pain diagnosis and pain management were not significantly different between the two groups (P > 0.05). Following the intervention, the mean score of pain diagnosis was 82 ± 19 in the lecture group and 97 ± 8 in the social networking app group (P < 0.01), and the mean pain management scores were 30 ± 17 and 90 ± 18 (P < 0.01), respectively.

Conclusion

This study showed that learning through a social networking app led to improved diagnosis and management of pain in mechanically-ventilated patients when compared with lectures. Training through social networking applications can therefore be considered as a feasible instructional method for developing nurses’ pain management skills.
Exploring trends in admissions and treatment for ankle fractures: a longitudinal cohort study of routinely collected hospital data in England
Authors: Scott Lauren J. , Jones Tim , Whitehouse Michael R. , Robinson Peter W. , Hollingworth William
Published: August 2020

Background

Evidence on the most effective and cost-effective management of ankle fractures is sparse but evolving. A recent large RCT in older patients with unstable fractures found that management with close-contact-casting was functionally equivalent and more cost-effective than internal fixation. We describe temporal and geographic variation in ankle fracture management and estimate the potential savings if close-contact-casting was used more often in older patients.

Methods

Patients admitted to hospital in England between 2007/08 and 2016/17 with an ankle fracture were identified using routine hospital episode statistics. We tested whether the use of internal fixation, and the proportion of internal fixations using intramedullary implants, changed over time. We estimated the potential annual cost savings if patients aged 60+ years were treated with close-contact-casting rather than internal fixation, in line with emerging evidence.

Results

Over the 10-year period, there were 223,465 hospital admissions with a primary ankle fracture diagnosis. The incidence (per 100,000) of internal fixation was fairly consistent over time in younger (33.2 in 2007/08, 30.9 in 2016/17) and older (36.5 in 2007/08, 37.4 in 2016/17) patients. The proportion of internal fixations which used intramedullary implants increased in both age groups (17.0–19.5% < 60 years; 15.2–17.4% 60+ years). In 2016/17, the cost of inpatient hospital care for ankle fractures in England was over £63.1million. If 50% of older patients who had an internal fixation instead had close-contact-casting, we estimate that approximately £1.56million could have been saved.

Conclusions

Despite emerging evidence that non-surgical and surgical management achieve equivalent functional outcomes in older patients, the rate of surgical fixation has remained relatively stable over the decade. The health service could achieve substantial savings if a higher proportion of older patients were treated with close-contact-casting, in line with recent evidence.
Precise base editing with CC context-specificity using engineered human APOBEC3G-nCas9 fusions
Authors: Liu Zhiquan , Chen Siyu , Shan Huanhuan , Jia Yingqi , Chen Mao , Song Yuning , Lai Liangxue , Li Zhanjun
Published: August 2020

Background

Cytidine base editors (CBEs), composed of a cytidine deaminase fused to Cas9 nickase (nCas9), enable efficient C-to-T conversion in various organisms. However, current base editors can induce unwanted bystander C-to-T conversions when multiple Cs are present in the ~ 5-nucleotide activity window of cytidine deaminase, which negatively affects their precision. Here, we develop a new base editor which significantly reduces unwanted bystander activities.

Results

We used an engineered human APOBEC3G (eA3G) C-terminal catalytic domain with preferential cytidine-deaminase activity in motifs with a hierarchy CCC>CCC>CC(where the preferentially deaminated C is underlined), to develop an eA3G-BE with distinctive CCcontext-specificity and reduced generation of bystander mutations. Targeted editing efficiencies of 18.3–58.0% and 54.5–92.2% with excellent CCcontext-specificity were generated in human cells and rabbit embryos, respectively. In addition, a base editor that can further recognize relaxed NG PAMs is achieved by combining hA3G with an engineered SpCas9-NG variant. The A3G-BEs were used to induce accurate single-base substitutions which led to nonsense mutation with an efficiency of 83–100% and few bystander mutations in Founder (F0) rabbits atTyrloci.

Conclusions

These novel base editors with improved precision and CCcontext-specificity will expand the toolset for precise gene modification in organisms.
The mTOR/ULK1 signaling pathway mediates the autophagy-promoting and osteogenic effects of dicalcium silicate nanoparticles
Authors: Ruolan Wang , Liangjiao Chen , Longquan Shao
Published: August 2020

A novel bioactive inorganic material containing silicon, calcium and oxygen, calcium silicate (Ca2SiO4, C2S) with a CaO-SiO2 ingredient, has been identified as a potential candidate for artificial bone. Autophagy has an essential function in adult tissue homoeostasis and tumorigenesis. However, little is known about whether silicate nanoparticles (C2S NPs) promote osteoblastic differentiation by inducing autophagy. Here we investigated the effects of C2S NPs on bone marrow mesenchymal stem cell differentiation (BMSCs) in osteoblasts. Furthermore, we identified the osteogenic gene and protein expression in BMSCs treated with C2S NPs. We found that autophagy is important for the ability of C2S NPs to induce osteoblastic differentiation of BMSCs. Our results showed that treatment with C2S NPs upregulated the expression of BMP2, UNX2, and OSX in BMSCs, and significantly promoted the expression of LC3 and Beclin, while P62 (an autophagy substrate) was downregulated. C2S NP treatment could also enhance Alizarin red S dye (ARS), although alkaline phosphatase (ALP) activity was not significantly changed. However, all these effects could be partially reversed by 3-MA. We then detected potential signaling pathways involved in this biological effect and found that C2S NPs could activate autophagy by suppressing mTOR and facilitating ULK1 expression. Autophagy further activated β-catenin expression and promoted osteogenic differentiation. In conclusion, C2S NPs promote bone formation and osteogenic differentiation in BMSCs by activating autophagy. They achieve this effect by activating mTOR/ULK1, inducing autophagy, and subsequently triggering the WNT/β-catenin pathway to boost the differentiation and biomineralization of osteoblasts.
Novel design of (PEG-ylated)PAMAM-based nanoparticles for sustained delivery of BDNF to neurotoxin-injured differentiated neuroblastoma cells
Authors: Dąbkowska Maria , Łuczkowska Karolina , Rogińska Dorota , Sobuś Anna , Wasilewska Monika , Ulańczyk Zofia , Machaliński Bogusław
Published: August 2020

Brain-derived neurotrophic factor (BDNF) is essential for the development and function of human neurons, therefore it is a promising target for neurodegenerative disorders treatment. Here, we studied BDNF-based electrostatic complex with dendrimer nanoparticles encapsulated in polyethylene glycol (PEG) in neurotoxin-treated, differentiated neuroblastoma SH-SY5Y cells, a model of neurodegenerative mechanisms. PEG layer was adsorbed at dendrimer-protein core nanoparticles to decrease their cellular uptake and to reduce BDNF-other proteins interactions for a prolonged time. Cytotoxicity and confocal microscopy analysis revealed PEG-ylated BDNF-dendrimer nanoparticles can be used for continuous neurotrophic factor delivery to the neurotoxin-treated cells over 24 h without toxic effect. We offer a reliable electrostatic route for efficient encapsulation and controlled transport of fragile therapeutic proteins without any covalent cross-linker; this could be considered as a safe drug delivery system. Understanding the polyvalent BDNF interactions with dendrimer core nanoparticles offers new possibilities for design of well-ordered protein drug delivery systems.
Further development in the assessment of psychological flexibility: validation of the German committed action questionnaire
Authors: Terhorst Yannik , Baumeister Harald , McCracken Lance M. , Lin Jiaxi
Published: August 2020

Background

Psychological flexibility is considered a fundamental aspect of health. It includes six interrelated facets: 1) cognitive defusion, 2) acceptance, 3) contact with the present moment, 4) self-as-context, 5) values, and 6) committed action. To gain further insight into psychological flexibility and its effects on health, reliable and valid instruments to assess all facets are needed. Committed action is one facet that is understudied. A long and short version of a validated measure (CAQ and CAQ-8) have been developed in English. Currently, there are no German versions of the CAQ. Aim of this study is to validate German-language versions of these in a chronic pain population.

Methods

The CAQ instructions and items were translated and evaluated in a chronic pain population (N = 181). Confirmatory factor analysis and Mokken scale analysis were conducted to evaluate the German questionnaires. Correlations with health outcomes, including quality of life (SF-12), physical and emotional functioning (MPI, BPI, PHQ-9, GAD-7), pain intensity, and with other facets of psychological flexibility (CPAQ, FAH-II) were investigated for convergent validity purposes. Scale reliability was assessed by the alpha, MS, lambda-2, LCRC, and omega coefficient.

Results

A bifactor model consisting of one general factor and two methodological factors emerged from the analysis. Criteria for reliability and validity were met. Medium to strong correlations to health outcomes and other facets of psychological flexibility were found. Results were similar to the original English version.

Conclusions

The present study presents a valid and reliable instrument to investigate committed action in German populations. Future studies could expand the present findings by evaluating the German CAQ versions in non-pain populations. The role of committed action and the wider psychological flexibility model in pain and other conditions deserves further investigation.
Burden of Care in Caregivers of Iranian patients with chronic disorders: a systematic review and meta-analysis
Authors: Rezaei Hayedeh , Niksima Seyed Hassan , Ghanei Gheshlagh Reza
Published: August 2020

Introduction

Caring for patients with chronic disorders can lead to different problems for caregivers in physical, psychological, social, family, and financial domains. High levels of burden of care can make caregivers vulnerable to physical and psychological conditions and influence their quality of life. Therefore, the goal of the present study was to estimate the overall percentage of burden of care in caregivers of Iranian patients with chronic disorders.

Methods

A total of 25 articles published from inception to February 2019 were reviewed. Search for articles was conducted in international (Scopus, Web of Science, and PubMed) and domestic (Scientific Information Database (SID) and MagIran) databases, using the following keywords: “Caregiver,” “Burden,” and “Iran,” and their possible combinations. The data were analyzed using the meta-analysis method and the random effects model. All the analyses were performed using STATA, version 14.

Results

The overall percentage of burden of care in caregivers of Iranian patients with chronic disorders was 53.28% (95% CI: 46.13–60.43). The highest percentage of burden of care was related to dialysis (62.75; 95% CI: 56.11–69.38), mental disorders (58.69; 95% CI: 49.70–67.69), and Alzheimer’s disease (57.07; 95% CI: 46.23–67.92), respectively; and the lowest percentage of burden of care was related to diabetes (34.92; 95% CI: 18.01–51.82).

Conclusions

Caregivers of Iranian patients with chronic disorders experience high levels of burden of care, especially those caring for patients undergoing dialysis, patients with mental disorders, and patients with Alzheimer’s disease. Therefore, necessary measures need to be taken by Iranian health care officials to reduce burden of care in caregivers.
The impact of health literacy on college students’ psychological disturbances and quality of life: a structural equation modeling analysis
Authors: Rababah Jehad A. , Al-Hammouri Mohammed M. , Drew Barbara L.
Published: August 2020

Background

The literature regarding the effect of health literacy on college students’ psychological health and quality of life is scarce. The purpose of conducting this cross-sectional study was to examine the effect of health literacy on certain psychological disturbances (perceived stress, depressive symptoms, and impulsivity) and quality of life of college students.

Methods

A cross-sectional quantitative design was utilized in this study. A total of 310 four-year college students participated in this study. The students completed a demographics questionnaire as well as already established and validated measures of health literacy, perceived stress, depressive symptoms, impulsivity, and quality of life. Structural equation modeling was performed to analyze the data to explore the effect of health literacy on the psychological disturbances and quality of life.

Results

The results showed that health literacy has a negative effect on three psychological disturbances commonly experienced by college students; perceived stress, depressive symptoms, and impulsivity. In addition, the effect of health literacy on the quality of life was positive.

Conclusion

The proposed conceptual model was supported. College students’ counseling staff could use the findings to better address students’ needs pertinent to psychological health and quality of life. Future research is warranted to develop a more comprehensive model that explains the role of health literacy in determining college students’ psychological health and quality of life.
The treatment strategy of R0 resection in colorectal cancer with synchronous para-aortic lymph node metastasis
Authors: Ushigome Hajime , Yasui Masayoshi , Ohue Masayuki , Haraguchi Naoaki , Nishimura Junichi , Sugimura Keijirou , Yamamoto Kazuyoshi , Wada Hiroshi , Takahashi Hidenori , Omori Takeshi , Miyata Hiroshi , Takiguchi Shuji
Published: August 2020

Background

Synchronous metastatic para-aortic lymph node (mPALN) dissectionin colorectal cancer has relatively good oncological outcomes, though many patients develop recurrence. Universal prognostic factor remain unclear and no definitive perioperative chemotherapy is available, making the treatment of mPALN controversial. In the present study, we aimed to establish a treatment strategy for synchronous mPALN.

Methods

This retrospective study involved 20 patients with pathological mPALN below the renal vein who underwent R0 resection. Long-term outcomes, recurrence type, and prognostic factors for survival were investigated.

Results

The 5-year overall survival and recurrence-free survival rates were 39% and 25%, respectively. Seventeen patients (85%) developed recurrence, including 13 (76%) within 1 year after surgery, and ~ 70% of all recurrences were multiple recurrences. Four patients (20%) survived > 5 years. Pathological T stage (p= 0.011), time to recurrence (p = 0.007), and recurrence resection (p = 0.009) were identified as prognostic factors for long-term survival.

Conclusions

R0 resection of synchronous mPALN in colorectal cancer resulted in acceptable oncological outcomes, though we found a high rate of early unresectable recurrence. If the recurrence occurs late or isolated, surgical resection should be considered for longer survival.
Communities of practice in Alberta Health Services: advancing a learning organisation
Authors: Auer Anna M. , Hanson Patricia , Brady-Fryer Barbara , Alati-it Julie , Johnson Allison L.
Published: August 2020

Background

In 2009, Alberta Health Services (AHS) became Canada’s first and largest fully integrated healthcare system, involving the amalgamation of nine regional health authorities and three provincial services. Within AHS, communities of practice (CoPs) meet regularly to learn from one another and to find ways to improve service quality. This qualitative study examined CoPs as an applied practice of a learning organisation along with their potential influence in a healthcare system by exploring the perspectives of CoP participants.

Methods

A collective case study method was used to enable the examination of a cross-section of cases in the study organisation. Semi-structured interviews were conducted with 31 participants representing 28 distinct CoPs. Using Senge’s framework of a learning organisation, CoP influences associated with team learning and organisational change were explored.

Results

CoPs in AHS were described as diverse in practice domains, focus, membership boundaries, attendance and sphere of influence. Using small-scale resource investments, CoPs provided members with opportunities for meaningful interactions, the capacity to build information pathways, and enhanced abilities to address needs at the point of care and service delivery. Overall, CoPs delivered a sophisticated array of engagement and knowledge-sharing activities perceived as supportive of organisational change, systems thinking, and the team learning practice critical to a learning organisation.

Conclusion

CoPs enable the diverse wealth of knowledge embedded in people, local conditions and special circumstances to flow from practice domain groups to programme and service areas, and into the larger system where it can effect organisational change. This research highlights the potential of CoPs to influence practice and broad-scale change more directly than previously understood or reported in the literature. As such, this study suggests that CoPs have the potential to influence and advance widespread systems change in Canadian healthcare.