bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of intracanal medicaments used in Endodontics on the dislocation resistance of two calcium silicate-based filling materials
Authors: Alsubait Sara , Alsaad Norah , Alahmari Sumayyah , Alfaraj Fatimah , Alfawaz Hussam , Alqedairi Abdullah
Published: February 2020

Background

Intracanal medicaments can be used in various endodontic conditions including multiple visit endodontics after trauma or in regenerative endodontics. These medicaments should be removed from the root canal before the placement of the filling or repair material. The aim of the present study was to evaluate the effect of prior calcium hydroxide (Ca(OH)2) and modified triple antibiotic paste (mTAP) placement on the push-out bond strength of TotalFill BC fast set putty (BC fast set putty) to root dentin when compared to mineral trioxide aggregate (MTA).

Methods

The root canals of 45 extracted mandibular premolars were prepared to a standardized internal diameter (1.5 mm). The specimens were randomly assigned to 3 groups according to the intracanal medicament used: mTAP (a mixture of metronidazole, ciprofloxacin, and cefaclor), Ca(OH)2, and no intracanal medicament. After 1 week, the medicaments were removed, and the middle third of the roots were cut into two transverse sections (2.0 ± 0.05) (n = 90 slices). Thereafter, the specimens were divided into two subgroups (n = 45 each): MTA or BC putty. After 1 week, the push-out test was performed and failure mode was evaluated. The data were statistically analyzed using two-way ANOVA and Tukey’s post hoc.

Results

The application of the intracanal medicament did not significantly affect the bond strength of BC putty (p > .05). For MTA, the prior application of Ca(OH)2 or mTAP significantly decreased the dislocation resistance (p < .05). Specimens in the MTA subgroups showed an almost equal number of cohesive and mixed types of failure while the majority of the specimens in the BC putty subgroups revealed the cohesive type.

Conclusions

Ca(OH)2 and mTAP promoted lower bond strength of MTA to root dentin compared to the control group. However, the BC fast set putty bond strength to dentin was not affected by prior medication with Ca(OH)2 or mTAP.
Implementation of the milestones communication approach for patients with limited prognosis: evaluation of intervention fidelity
Authors: Bossert Jasmin , Wensing Michel , Thomas Michael , Villalobos Matthias , Jung Corinna , Siegle Anja , Hagelskamp Laura , Deis Nicole , Jünger Jana , Krug Katja
Published: February 2020

Background

Despite improvements in diagnostics and therapy, the majority of lung tumours are diagnosed at advanced stage IV with a poor prognosis. Due to the nature of an incurable disease, patients need to engage in shared decision making on advance care planning. To implement this in clinical practice, effective communication between patients, caregivers and healthcare professionals is essential. The Heidelberg Milestones Communication Approach (MCA) is delivered by a specifically trained interprofessional tandem and consists of four milestone conversations (MCs) at pivotal times in the disease trajectory. MC 1 (Diagnosis): i.e. prognosis; MC 2 (Stable disease): i.e. prognostic awareness; MC 3 (Progression): i.e. reassessment; MC 4 (Best supportive care): i.e. end of treatment. In between MCs, follow-up calls are carried out to sustain communication. This study aimed to assess to what extent the MCA was implemented as planned and consolidated in specialized oncology practice.

Methods

A prospective observational process evaluation study was conducted, which focused on the implementation fidelity of the MCA. All MCs during two assessment periods were included. We analysed all written records of the conversations, which are part of the routine documentation during MCs and follow-up calls. Adherence to key aspects of the manual was documented on structured checklists at the beginning of the implementation of the MCA and after 6 months. The analysis was descriptive. Differences between the two assessment periods are analysed with chi-square tests.

Results

A total of 133 MCs and 54 follow-up-calls (t1) and of 172 MCs and 92 follow-up calls (t2) were analysed. MC 2 were the most frequently completed conversations (n = 51 andn = 47). Advance care planning was discussed in 26 and 13% of MC 2 in the respective assessment periods; in 31 and 47% of MC 2, prognostic awareness was recorded. The most frequently documented topic in the follow-up calls was the physical condition in patients (82 and 83%).

Conclusion

The implementation of a trajectory-specific communication concept was largely successful. Additional studies are needed to understand how fidelity could be further improved.

Trial registration

DRKS00013469/ Date of registration: 22.12.2017.
Investigating the effect of vitamin D vaginal suppository on sexual function among postmenopausal women: study protocol for a randomized controlled trial
Authors: Sarebani Zinat , Alimoradi Zainab , Aali Ehsan , Mirzadeh Monirsadat , Chegini Venus , Abbaspour Mohammadreza , Griffiths Mark D.
Published: February 2020

Background

Menopause is associated with changes in sexual function which are partly due to vaginal atrophy in response to estrogen reduction. Estrogen administration temporarily reduces the symptoms of vaginal dryness, but long-term exposure to this drug is likely to be associated with serious complications. Considering the promising results of previous studies concerning the effect of vitamin D on vaginal dryness, the proposed study will investigate the effect of vitamin D vaginal suppository on the sexual function of postmenopausal women.

Methods

In a randomized, controlled clinical trial, 105 postmenopausal women will be randomly assigned to three groups receiving vitamin D vaginal suppository, placebo vaginal suppository, or control (no intervention). Vitamin D vaginal suppositories contain 1000 units of vitamin D3. The timing of the use of vitamin D vaginal suppositories and placebo suppositories will be every night in the first 2 weeks, and every other night in the following 6 weeks (8 weeks in total). The primary outcome will be the sexual function of participants which will be assessed using the Female Sexual Function Index (FSFI) before and immediately after the intervention, and at 1 and 2 months after the end of the intervention. The side effects of these suppositories will be examined as a secondary consequence of the study. Data will be analyzed using SPSS software version 25. In the case of normal distribution of data, the mean score of sexual function will be compared between the groups using a repeated measurements ANOVA. If statistical analysis leads to significant results, the post-hoc test will be used to determine the differences between the groups. Comparison of demographic and fertility characteristics of the women will be carried out using statistical tests such as chi-squares and t-tests. A significance level of p < .05 will be used for statistical analyses.

Discussion

If vitamin D vaginal suppositories improve sexual function among premenopausal women with long-term effects and minimum side effects, the suppositories will be considered a safe complementary and alternative choice for alleviating sexual dysfunction among this group.

Trial registration

IRCT20180704040346N1 at 2018-10-13 prospectively registered.
Association between clinic physician workforce and avoidable readmission: a retrospective database research
Authors: Hirota Yoshito , Kunisawa Susumu , Fushimi Kiyohide , Imanaka Yuichi
Published: February 2020

Background

To reduce hospitalization costs, it is necessary to prevent avoidable hospitalization as well as avoidable readmission. This study aimed to examine the relationship between clinic physician workforce and unplanned readmission for ambulatory care sensitive conditions (ACSCs).

Methods

The present study was a retrospective database research using nationwide administrative claims database of acute care hospitals in Japan. We identified patients aged ≥65 years who were admitted with ACSCs from home and discharged to home between April 2014 and December 2014 (n = 127,209). The primary outcome was unplanned readmission for ACSCs within 30 or 90 days of hospital discharge. A hierarchical logistic regression model was developed with patients at the first level and regions (secondary medical service areas) at the second level.

Results

The 30-day and 90-day ACSC-related readmission rates were 3.7 and 4.6%, respectively. The high full-time equivalents (FTEs) of clinic physicians per 100,000 population were significantly associated with decreased odds ratios for 30-day and 90-day ACSC-related readmissions. This association did not change even when sensitivity analyses was conducted.

Conclusions

Among patients who had history of admission for ACSCs, greater clinic physician workforce prevented the incidence of readmission because of ACSCs. Regional medical plans to prevent avoidable readmissions should incorporate policy interventions that focus on the clinic physician workforce.
Dromedary camel CD14high MHCIIhigh monocytes display inflammatory properties and are reduced in newborn camel calves
Authors: Hussen Jamal , Shawaf Turke , Al-Mubarak Abdullah I. A. , Al Humam Naser Abdallah , Almathen Faisal , Schuberth Hans-Joachim
Published: February 2020

Background

In human and different animal species, blood monocytes are classified based on their expression pattern of different monocytic markers into phenotypically and functionally different subsets. In the current study, we used flow cytometry and monoclonal antibodies to CD172a, CD14, CD163 and MHCII to identify monocyte subsets in peripheral blood of dromedary camels.

Results

Based on CD14, CD163 and MHCII expression, camel CD172a + monocytes were divided into three subsets: The major subpopulation of camel monocytes (mo-I) showed high expression of CD14 and CD163, but low expression of MHCII. A second subset of monocytes (mo-II) expressed highly all three markers, CD14, CD163 and MHCII. A third monocyte subset (mo-III) displayed low expression of CD14 and CD163 with high MHCII expression. While the two MHCIIhigh subsets (mo-II and mo-III) showed higher expression of CD11a in comparison to the MHCIIlow subset (mo-I), CD18 and CD11b were highest expressed on the two CD14high subsets (mo-I and mo-II). Bacterial stimulation of camel leukocytes identified mo-II cells as an antimicrobial monocyte subset with the highest phagocytic and ROS production capacity. The comparison of monocyte counts and phenotype between newborn calves and adult camels revealed significantly reduced numbers of mo-II cells in newborn animals. Monocytes of newborns expressed significantly more CD172a and CD163 molecules but less CD14 and MHCII molecules than monocytes of adult camels.

Conclusions

Camel monocyte subsets, mo-I, mo-II and mo-III are counterparts of bovine classical, intermediate and non-classical monocytes respectively. The distribution of camel monocyte subsets is influenced by age.
Exploring and analysing single cell multi-omics data with VDJView
Authors: Samir Jerome , Rizzetto Simone , Gupta Money , Luciani Fabio
Published: February 2020

Background

Single cell RNA sequencing provides unprecedented opportunity to simultaneously explore the transcriptomic and immune receptor diversity of T and B cells. However, there are limited tools available that simultaneously analyse large multi-omics datasets integrated with metadata such as patient and clinical information.

Results

We developed VDJView, which permits the simultaneous or independent analysis and visualisation of gene expression, immune receptors, and clinical metadata of both T and B cells. This tool is implemented as an easy-to-use R shiny web-application, which integrates numerous gene expression and TCR analysis tools, and accepts data from plate-based sorted or high-throughput single cell platforms. We utilised VDJView to analyse several 10X scRNA-seq datasets, including a recent dataset of 150,000 CD8+T cells with available gene expression, TCR sequences, quantification of 15 surface proteins, and 44 antigen specificities (across viruses, cancer, and self-antigens). We performed quality control, filtering of tetramer non-specific cells, clustering, random sampling and hypothesis testing to discover antigen specific gene signatures which were associated with immune cell differentiation states and clonal expansion across the pathogen specific T cells. We also analysed 563 single cells (plate-based sorted) obtained from 11 subjects, revealing clonally expanded T and B cells across primary cancer tissues and metastatic lymph-node. These immune cells clustered with distinct gene signatures according to the breast cancer molecular subtype. VDJView has been tested in lab meetings and peer-to-peer discussions, showing effective data generation and discussion without the need to consult bioinformaticians.

Conclusions

VDJView enables researchers without profound bioinformatics skills to analyse immune scRNA-seq data, integrating and visualising this with clonality and metadata profiles, thus accelerating the process of hypothesis testing, data interpretation and discovery of cellular heterogeneity. VDJView is freely available athttps://bitbucket.org/kirbyvisp/vdjview.
Prevalence and distribution patterns of allergens among children with asthma and asthma-like symptoms in Shanghai, China
Authors: Mao Song , Wu Liangxia , Shi Wenjing
Published: February 2020

Objective

We aimed to identify the prevalence and distribution patterns of allergens among Chinese children with asthma/asthma-like symptoms (ALS).

Methods

A total of 3479 children with asthma/ALS were enrolled. Skin prick test (SPT) was used to test the allergen-specific IgE. We analysed allergens prevalence and distribution, and its relationship with demographic characteristics.

Results

Aeroallergens prevalence was higher than that of food allergens (p < 10− 4). Boys had higher aeroallergens prevalence than that in girls (p < 10− 4). Significant difference of aeroallergens prevalence among cases with different parental allergy history was observed (p < 10− 4). Age was positively associated with aeroallergens prevalence before the age of 11.5 (P < 10− 4), particularly before the age of 2.42 (P < 10− 4). Age was negatively associated with aeroallergens prevalence after the age of 11.5 (P = 0.021). Age was negatively associated with food allergens prevalence before the age of 3.42 (P < 10− 4). Age was associated with the intensity of dermatophagoides farinae (DF)/house dust mite (HDM) allergens (P < 10− 4). Age was negatively associated with the intensity of shrimp, and crab allergens before the age of 3.3 and 3.3, respectively (P = 0.012, < 10− 4). Boys had higher intensity of DF and HDM allergens than that in girls (P < 10− 4, P < 10− 4). Significant differences of the intensity of DF and HDM allergens among groups with different parental allergy history were noted (P < 10− 4, P < 10− 4).

Conclusions

Boys and parental allergy history were associated with higher prevalence and intenstity of aeroallergens. Age was positively and negatively associated with aeroallergens prevalence before and after the age of 11.5, respectively. Age was negatively associated with food allergens prevalence before the age of 3.42.
Increased risk of cardiovascular mortality by strict glycemic control (pre-procedural HbA1c < 6.5%) in Japanese medically-treated diabetic patients following percutaneous coronary intervention: a 10-year follow-up study
Authors: Funamizu Takehiro , Iwata Hiroshi , Nishida Yuya , Miyosawa Katsutoshi , Doi Shinichiro , Chikata Yuichi , Shitara Jun , Endo Hirohisa , Wada Hideki , Naito Ryo , Ogita Manabu , Dohi Tomotaka , Kasai Takatoshi , Okazaki Shinya , Isoda Kikuo , Miyauchi Katsumi , Daida Hiroyuki
Published: February 2020

Background

In the secondary prevention of cardiovascular (CV) disease in patients with diabetes, an optimal level of HbA1c, the most widely-used glycemic control indicator, for favorable clinical consequences still remains to be established. This study assessed the association between preprocedural HbA1c level and CV mortality in Japanese diabetic patients undergoing percutaneous coronary intervention (PCI).

Methods

This is a retrospective observational study using a single-center prospective PCI database involving consecutive 4542 patients who underwent PCI between 2000 and 2016. Patients with any antidiabetic medication including insulin at PCI were included in the analysis (n = 1328). We divided the patients into 5 and 2 groups according to HbA1c level; HbA1c: < 6.5% (n = 267), 6.5–7.0% (n = 268), 7.0–7.5% (n = 262), 7.5–8.5% (n = 287) and ≥ 8.5% (n = 244), and 7.0% > and ≤ 7.0%, respectively. The primary outcome was CV mortality including sudden death. The median follow-up duration was 6.2 years.

Results

In the follow-up period, CV and sudden death occurred in 81 and 23 patients, respectively. While unadjusted Kaplan–Meier analysis showed no difference in cumulative CV mortality rate between patients binarized by preprocedural HbA1c 7.0%, analysis of the 5 groups of HbA1c showed significantly higher cumulative CV death in patients with HbA1c < 6.5% compared with those with 7.0–7.5% (P = 0.042). Multivariate Cox hazard analysis revealed a U-shaped relationship between preprocedural HbA1c level and risk of CV death, and the lowest risk was in the HbA1c 7.0–7.5% group (Hazard ratio of HbA1c < 6.5% compared to 7.0–7.5%: 2.97, 95% confidence interval: 1.33–7.25, P = 0.007). Similarly, univariate analysis revealed the lowest risk of sudden death was in the HbA1c 7.0–7.5% group.

Conclusion

The findings indicate an increased risk of CV mortality by strict glycemic control (HbA1c < 6.5%) in the secondary prevention of CV disease in Japanese patients with medically-treated diabetes.

Trial registration This study reports the retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians’ Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry UMIN-CTR 000035587).
Long noncoding RNA RHPN1-AS1 promotes colorectal cancer progression via targeting miR-7-5p/OGT axis
Authors: Zheng Wei , Li Hui , Zhang Hui , Zhang Chao , Zhu Zhonglin , Liang Hong , Zhou Yifeng
Published: February 2020

Background

Rhophilin Rho GTPase binding protein 1 antisense RNA 1 (RHPN1-AS1) is a newly discovered oncogene in several diseases, such as breast cancer, non-small cell lung cancer and uveal melanoma. Nevertheless, its molecular role in colorectal cancer (CRC) remains unknown. This paper explored the role of RHPN1-AS1 in CRC progression.

Methods

qRT-PCR was used to detect relevant RNAs expression. CCK-8, EdU, flow cytometry, Transwell and western blot assays were performed to investigate the function of RHPN1-AS1 in CRC cells. Xenograft model was constructed to evaluate the effects of RHPN1-AS1 on tumor growth in vivo. Mechanical experiments were performed to investigate the relationship between relative genes.

Results

RHPN1-AS1 was significantly overexpressed in CRC cell lines. Knockdown of RHPN1-AS1 could inhibit cell proliferation, while stimulating cell apoptosis in vitro. Cell migration and invasion abilities were greatly suppressed after silencing RHPN1-AS1. Besides, signal transducer and activator of transcription 3 (STAT3) served as transcription factor of RHPN1-AS1. Moreover, miR-7-5p was identified as a target of RHPN1-AS1 and was negatively regulated by RHPN1-AS1 in CRC. MiR-7-5p inhibition rescued the oncogenic function of RHPN1-AS1. Additionally, O-GlcNAcylation transferase (OGT) was the downstream target of miR-7-5p. OGT overexpression could abrogate the anti-tumor effects of RHPN1-AS1 knockdown on CRC.

Conclusion

RHPN1-AS1 regulates CRC by mediating OGT through sponging miR-7-5p, suggesting that RHPN1-AS1 might be a potential therapeutic target for CRC.
Caveolin-2 is regulated by BRD4 and contributes to cell growth in pancreatic cancer
Authors: Jiao Feng , Han Ting , Yuan Cuncun , Liang Yiyi , Cui Jiujie , Zhuo Meng , Wang Liwei
Published: February 2020

Background

The bromodomain and extra-terminal domain (BET) family of proteins, especially BRD4 play an important role in epigenetic regulation, and are essential for cell survival and also are promising anticancer targets. This study aims to analyze the effect of BRD4 on the cell growth and progression of pancreatic cancer and novel mechanisms involved.

Methods

Expression of BRD4 in pancreatic cancer and paired adjacent noncancerous tissues from 76 patients was analyzed by western blotting, immunohistochemistry, and real time PCR. Its correlation with the clinicopathological characteristics and prognosis of pancreatic cancer patients was analyzed. The effects of BRD4 on the cell proliferation were detected by colony formation assay and sulforhodamine B assay. Migration and invasion were determined by Transwell assays, and the effect of BRD4 on subcutaneous tumor formation was verified in nude mice. Cell cycle analysis was detected by flow cytometry. The potential downstream targets of BRD4 and related molecular mechanisms were clarified by RNA sequencing, chromatin immunoprecipitation and dual luciferase reporter assay.

Results

BRD4 was overexpressed in pancreatic cancer. Biological results showed that BRD4 functioned as tumor promoter, facilitated cell proliferation, migration and invasion in vitro and in vivo. Further, caveolin-2 was selected as the downstream gene of BRD4 by RNA sequencing. Caveolin-2 overexpression can partially reverse the decreased cell growth ability caused by BRD4 knockdown, but did not affect cell migration and invasion. Chromatin immunoprecipitation assay and dual luciferase reporter assay revealed BRD4 could bind to the promoter region of caveolin-2 and upregulate caveolin-2 expression. Clinical data further indicated a positive correlation between BRD4 and caveolin-2 expression. BRD4 (high)/caveolin-2 (high) correlated with shorter overall survival of patients with pancreatic cancer. Multivariate analysis revealed that both BRD4 and caveolin-2 were independent factors.

Conclusions

Our findings reveal the oncogenic effects of BRD4 in pancreatic cancer and elucidate a possible mechanism by which BRD4 and caveolin-2 act to enhance cell growth. Targeting the BRD4-caveolin-2 interaction by development of BET inhibitors will be a therapeutic strategy for pancreatic cancer.
Integrated characterization and validation of the prognostic significance of microRNA-200s in colorectal cancer
Authors: Peng Qiliang , Cheng Ming , Li Ting , Chen Xiangying , Shen Yi , Zhu Yaqun , Xu Bo
Published: February 2020

Background

Accumulating evidence has demonstrated that microRNA-200s (miR-200a, miR-200b and miR-200c) could serve as promising molecular biomarkers for cancer prognosis. Nevertheless, the associations between miR-200s expression and colorectal cancer (CRC) prognosis remain controversial.

Methods

We applied two mainstream approaches combining meta-analysis and bioinformatics analysis to answer whether miR-200s were associated with the prognosis of CRC patients and why miR-200s could be used as prognostic biomarkers for CRC.

Results

Consequently, low expression of miR-200s was associated with unfavorable overall survival (OS) in CRC patients (HR: 1.09; 95% CI 1.01–1.17; P = 0.025). According to the subgroup analysis, the prognostic role of miR-200s was more significant for tissue samples, large samples, American patients and miR-200a subgroups. Then the target genes of miR-200s were predicted and applied for functional enrichment analyses. The results showed that the target genes of miR-200s were mainly enriched into some vital ontology subjects such as regulation ability, key cell structures and binding function. Moreover, a series of important signaling pathways were identified, which were significantly linked with the initiation and progression of CRC. Additionally, a protein‑protein interaction (PPI) network of miR-200s targets was constructed to screen hub genes and modules. The identified hub genes and modules were validated to be highly involved in the occurrence and development of CRC.

Conclusions

Current evidences revealed that miR-200s could be promising biomarkers for CRC prognosis. However, the findings still need to be validated with more larger-scale prospective studies and biological experiments before miR-200s could be applied into clinical application.
Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda
Authors: Balikagala Betty , Sakurai-Yatsushiro Miki , Tachibana Shin-Ichiro , Ikeda Mie , Yamauchi Masato , Katuro Osbert T. , Ntege Edward H. , Sekihara Makoto , Fukuda Naoyuki , Takahashi Nobuyuki , Yatsushiro Shouki , Mori Toshiyuki , Hirai Makoto , Opio Walter , Obwoya Paul S. , Anywar Denis A. , Auma Mary A. , Palacpac Nirianne M. Q. , Tsuboi Takafumi , Odongo-Aginya Emmanuel I. , Kimura Eisaku , Ogwang Martin , Horii Toshihiro , Mita Toshihiro
Published: February 2020

Background

Usage of chloroquine was discontinued from the treatment of Plasmodium falciparum infection in almost all endemic regions because of global spread of resistant parasites. Since the first report in Malawi, numerous epidemiological studies have demonstrated that the discontinuance led to re-emergence of chloroquine-susceptible P. falciparum, suggesting a possible role in future malaria control. However, most studies were cross-sectional, with few studies looking at the persistence of chloroquine recovery in long term. This study fills the gap by providing, for a period of at least 6 years, proof of persistent re-emergence/stable recovery of susceptible parasite populations using both molecular and phenotypic methods.

Methods

Ex vivo drug-susceptibility assays to chloroquine (n = 319) and lumefantrine (n = 335) were performed from 2013 to 2018 in Gulu, Northern Uganda, where chloroquine had been removed from the official malaria treatment regimen since 2006. Genotyping of pfcrt and pfmdr1 was also performed.

Results

Chloroquine resistance (≥ 100 nM) was observed in only 3 (1.3%) samples. Average IC50 values for chloroquine were persistently low throughout the study period (17.4–24.9 nM). Parasites harbouring pfcrt K76 alleles showed significantly lower IC50s to chloroquine than the parasites harbouring K76T alleles (21.4 nM vs. 43.1 nM, p-value = 3.9 × 10−8). Prevalence of K76 alleles gradually increased from 71% in 2013 to 100% in 2018.

Conclusion

This study found evidence of stable persistence of chloroquine susceptibility with the fixation of pfcrt K76 in Northern Uganda after discontinuation of chloroquine in the region. Accumulation of similar evidence in other endemic areas in Uganda could open channels for possible future re-use of chloroquine as an option for malaria treatment or prevention.
Assessment of Plasmodium falciparum drug resistance molecular markers from the Blue Nile State, Southeast Sudan
Authors: Mohamed Abdelrahim O. , Hussien Maazza , Mohamed Amal , Suliman Abdelmaroof , Elkando Nuha S. , Abdelbagi Hanadi , Malik Elfatih M. , Abdelraheem Mohammed H. , Hamid Muzamil Mahdi Abdel
Published: February 2020

Background

Plasmodium falciparum malaria is a public health problem worldwide. Malaria treatment policy has faced periodic changes due to emergence of drug resistant parasites. In Sudan chloroquine has been replaced by artesunate and sulfadoxine/pyrimethamine (AS/SP) in 2005 and to artemether–lumefantrine (AL) in 2017, due to the development of drug resistance. Different molecular markers have been used to monitor the status of drug resistant P. falciparum. This study aimed to determine the frequency of malaria drug resistance molecular markers in Southeast Sudan.

Methods

The samples of this study were day zero dried blood spot samples collected from efficacy studies in the Blue Nile State from November 2015 to January 2016. A total of 130 samples were amplified and sequenced using illumina Miseq platform. The molecular markers included were Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfk13, exonuclease and artemisinin resistant (ART‐R) genetic background (Pfmdr2, ferroredoxine, Pfcrt and Pfarps10).

Results

Resistance markers for chloroquine were detected in 25.8% of the samples as mutant haplotype Pfcrt 72-76 CVIET and 21.7% Pfmdr1 86Y. Pfdhfr mutations were detected in codons 51, 59 and 108. The ICNI double-mutant haplotype was the most prevalent (69%). Pfdhps mutations were detected in codons 436, 437, 540, 581 and 613. The SGEGA triple-mutant haplotype was the most prevalent (43%). In Pfdhfr/Pfdhps combined mutation, quintuple mutation ICNI/SGEGA is the most frequent one (29%). Six of the seven treatment failure samples had quintuple mutation and the seventh was quadruple. This was significantly higher from the adequately responsive group (P < 0.01). Pfk13 novel mutations were found in 7 (8.8%) samples, which were not linked to artemisinin resistance. Mutations in ART‐R genetic background genes ranged from zero to 7%. Exonuclease mutation was not detected.

Conclusion

In this study, moderate resistance to chloroquine and high resistance to SP was observed. Novel mutations of Pfk13 gene not linked to treatment failure were described. There was no resistance to piperaquine the partner drug of dihydroartemisinin/piperaquine (DHA-PPQ).
Determinants for early introduction of complementary foods in Australian infants: findings from the HSHK birth cohort study
Authors: Arora Amit , Manohar Narendar , Hector Debra , Bhole Sameer , Hayen Andrew , Eastwood John , Scott Jane Anne
Published: February 2020

Objective

The purpose of this study was to examine the timing of introduction of complementary (solid) foods among infants in South Western Sydney, Australia, and describe the maternal and infant characteristics associated with very early introduction of solids.

Methods

Mother-infant dyads (n = 1035) were recruited into the “Healthy Smiles Healthy Kids” study by Child and Family Health Nurses at the first post-natal home visit. Data collected via telephone interviews at 8, 17, 34 and 52 weeks postpartum included timing of introduction of solids and a variety of maternal and infant characteristics (n = 934). Multiple logistic regression was used to identify factors independently associated with the risk of introducing solids very early, which for the purpose of this study was defined as being before 17 weeks.

Results

The median age of introduction of solids was 22 weeks. In total, 13.6% (n = 127) of infants had received solids before 17 weeks and 76.9% (n = 719) before 26 weeks of age. The practice of introducing solids early decreased with older age of the mother. Compared to women < 25 years of age, those who were 35 years or older were 72% less likely to introduce solids very early (OR = 0.28, CI95 0.14–0.58). Single mothers had more than twice the odds of introducing solids before the age of 17 weeks compared to married women (OR = 2.35, CI95 1.33–4.16). Women who had returned to work between 6 to 12 months postpartum were 46% less likely to introduce solids very early compared with those who were not working at the child’s first birthday (OR = 0.54, CI95 0.30–0.97). Women born in Vietnam and Indian sub-continent had lower odds of introducing solids very early compared to Australian born women (OR = 0.42, CI95 0.21–0.84 and OR = 0.30, CI95 0.12–0.79, respectively). Infants who were exclusively formula-fed at 4 weeks postpartum had more than twice the odds of receiving solids very early (OR = 2.34, CI95 1.49–3.66).

Conclusions

Women who are younger, single mothers, those not working by the time of child’s first birthday, those born in Australia, and those who exclusively formula-feed their babies at 4 weeks postpartum should be targeted for health promotion programs that aim to delay the introduction of solids in infants to the recommended time.
Data anomalies and apparent reporting errors in ‘Randomized controlled trial testing weight loss and abdominal obesity outcomes of moxibustion’
Authors: Mestre Luis M. , Dickinson Stephanie L. , Golzarri-Arroyo Lilian , Brown Andrew W. , Allison David B.
Published: February 2020

Randomized Controlled Trials (RCTs) are the best method to determine causal effects for treatments if they are well done and well reported. Good evidence about proposed treatments for obesity is needed, and Hsieh et al. (Biomed Eng Online 17:149, 2018) are to be commended for putting moxibustion to the test. However, careful evaluation of the paper reveals inconsistencies and apparent reporting errors, which raise doubts about conclusions from the study.
Iron oxides nanoparticles (IOs) exposed to magnetic field promote expression of osteogenic markers in osteoblasts through integrin alpha-3 (INTa-3) activation, inhibits osteoclasts activity and exerts anti-inflammatory action
Authors: Marycz K. , Sobierajska P. , Roecken M. , Kornicka-Garbowska K. , Kępska M. , Idczak R. , Nedelec J.-M. , Wiglusz R. J.
Published: February 2020

Background

Prevalence of osteoporosis is rapidly growing and so searching for novel therapeutics. Yet, there is no drug on the market available to modulate osteoclasts and osteoblasts activity simultaneously. Thus in presented research we decided to fabricate nanocomposite able to: (i) enhance osteogenic differentiation of osteoblast, (i) reduce osteoclasts activity and (iii) reduce pro-inflammatory microenvironment. As a consequence we expect that fabricated material will be able to inhibit bone loss during osteoporosis.

Results

The α-Fe2O3/γ-Fe2O3nanocomposite (IOs) was prepared using the modified sol–gel method. The structural properties, size, morphology and Zeta-potential of the particles were studied by means of XRPD (X-ray powder diffraction), SEM (Scanning Electron Microscopy), PALS and DLS techniques. The identification of both phases was checked by the use of Raman spectroscopy and Mössbauer measurement. Moreover, the magnetic properties of the obtained IOs nanoparticles were determined. Then biological properties of material were investigated with osteoblast (MC3T3), osteoclasts (4B12) and macrophages (RAW 264.7) in the presence or absence of magnetic field, using confocal microscope, RT-qPCR, western blot and cell analyser. Here we have found that fabricated IOs: (i) do not elicit immune response; (ii) reduce inflammation; (iii) enhance osteogenic differentiation of osteoblasts; (iv) modulates integrin expression and (v) triggers apoptosis of osteoclasts.

Conclusion

Fabricated by our group α-Fe2O3/γ-Fe2O3nanocomposite may become an justified and effective therapeutic intervention during osteoporosis treatment.
Triazine-cored polymeric vectors for antisense oligonucleotide delivery in vitro and in vivo
Authors: Wang Mingxing , Wu Bo , Tucker Jason D. , Shah Sapana N. , Lu Peijuan , Lu Qilong
Published: February 2020

Background

The polymer-based drug/gene delivery is promising for the treatment of inherent or acquire disease, because of the polymer’s structural flexibility, larger capacity for therapeutic agent, low host immunogenicity and less cost. Antisense therapy is an approach to fighting genetic disorders or infections using antisense oligonucleotides (AOs). Unfortunately, the naked AOs showed low therapeutic efficacy in vivo and in clinical trial due to their poor cellular uptake and fast clearance in bloodstream. In this study, a series of triazine-cored amphiphilic polymers (TAPs) were investigated for their potential to enhance delivery of AOs, 2′-O-methyl phosphorothioate RNA (2′-OMePS) and phosphorodiamidate morpholino oligomer (PMO) both in vitro and in vivo.

Results

TAPs significantly enhanced AO-induced exon-skipping in a GFP reporter-based myoblast and myotube culture system, and observed cytotoxicity of the TAPs were lower than Endoporter, Lipofectamine-2000 or PEI 25K. Application of optimized formulations of TAPs with AO targeted to dystrophin exon 23 demonstrated a significant increase in exon-skipping efficiency in dystrophic mdx mice. The best ones for PMO and 2′-OMePS delivery have reached to 11-, 15-fold compared with the AO only in mdx mice, respectively.

Conclusion

The study of triazine-cored amphiphilic polymers for AO delivery in vitro and in mdx mice indicated that the carrier’s performances are related to the molecular size, compositions and hydrophilic-lipophilic balance (HLB) of the polymers, as well as the AO’s structure. Improved exon-skipping efficiency of AOs observed in vitro and in mdx mice accompanied with low cytotoxicity demonstrated TAP polymers are potentials as safe and effective delivery carrier for gene/drug delivery.
Factors affecting the quality of life in women with gestational diabetes mellitus: a path analysis model
Authors: Ansarzadeh Soheila , Salehi Leili , Mahmoodi Zohreh , Mohammadbeigi Abolfazl
Published: February 2020

Background

Quality of life (QoL) is the most important indicator for assessing the status of health care in chronic diseases. The present study aimed to determine the pathway determinants model of QoL in patients with gestational diabetes mellitus (GDM).

Methods

This cross-sectional study was conducted on 329 women with GM referred to health care centers in Qom, Iran during 2018. Convenience sampling methods was used. Inclusion criteria were: afflicted by GM and received pregnancy care services from health center. Several questionnaires (Knowledge, attitude, self-efficacy (SE), social support (SS), pregnancy distress, self-management(SM) and QoL) were used for data collection. Data were analyzed with SPSS-21 and Lisrel-8.8 software using statistical path analysis.

Results

The mean age of participants was 30.93 ± 5.42 years. The final path model fitted well (CFI =1, RMSEA = 0.0003) and showed that, only age variable from both direct and indirect path had an impact on QoL (B = 0.51). Among variables that directly affected the QoL, SS had the highest effect (B = 1.02) and SE (B = 0.01) had the lowest effect. In the indirect path, only the knowledge variable by affecting the SE had an impact on the QoL (B = 0.0045).

Conclusion

SS had the greatest impact on the QoL. Obviously, providing all the requirements to support patients can help them overcome problems and improve their QoL. Distress negatively affects the QoL through SM and it should be noticed in interventional studies.
Development of a toolkit for educators of the wheelchair service provision process: the Seating and Mobility Academic Resource Toolkit (SMART)
Authors: Rushton Paula W. , Fung Karen , Gauthier Mélina , Goldberg Mary , Toro Maria , Seymour Nicky , Pearlman Jon
Published: February 2020

Background

Insufficient wheelchair training among rehabilitation professionals has been identified as an important factor that hinders access to appropriate wheelchair services. The aim of this study was to develop a toolkit to promote the integration of wheelchair education into academic curricula of rehabilitation programs.

Methods

A participatory action research design was carried out in three phases: (1) development of the Initial and Alpha Versions involving secondary analyses of surveys (n = 72), interviews (n = 14), and academic training partners meeting presentations (n = 16); (2) development of the Beta Version based on feedback from collaborators (n = 21); and (3) development of the Launch Version based on feedback from participants attending presentations of the Beta Version at conferences, symposiums, and webinars (n = 94).

Results

Over 100 individuals participated in reviews of the Seating and Mobility Academic Resource Toolkit (SMART). Initial development addressed modifiable factors that perpetuate insufficient wheelchair education in academic curricula (e.g., limited awareness, limited expertise). Internal feedback on the web-based Alpha Version resulted in modifications of appearance and multimedia, structure and design, and navigation. External feedback then led primarily to fine-tuning the navigation of SMART. Positive reviews were received from global wheelchair professionals (i.e., educators, researchers, clinicians). The Launch Version of the SMART (smart.wheelchairnetwork.org) provides a forum for sharing and accessing resources to inform the integration and enhancement of wheelchair content into university rehabilitation programs.

Conclusions

As an open-source open-access online “living document,” SMART has the potential to promote the integration of wheelchair service provision education into academic curricula of rehabilitation programs. Future studies will explore the ease of use and the effectiveness of the SMART.
Uganda’s laboratory human resource in the era of global health initiatives: experiences, constraints and opportunities—an assessment of 100 facilities
Authors: Kiwanuka Suzanne N. , Namuhani Noel , Akulume Martha , Kalyesubula Simeon , Bazeyo William , Kisakye Angela N.
Published: February 2020

Introduction

Laboratories are vital in disease diagnosis, prevention, treatment and outbreak investigations. Although recent decades have seen rapid advancements in modernised equipment and laboratory processes, minimal investments have been made towards strengthening laboratory professionals in Africa. This workforce is characterised by insufficient numbers, skewed rural-urban distribution, inadequate qualifications, inadequate skill-mix and limited career opportunities. These factors adversely affect the performance of laboratory professionals, who are the backbone of quality services. In the era of Global Health Initiatives, this study describes the status of laboratory human resource and assesses the experiences, constrains and opportunities for strengthening them in Uganda.

Methods

This paper is part of a study, which assessed laboratory capacity in 21 districts during December 2015 to January 2016. We collected data using a laboratory assessment tool adapted from the WHO and USAID assessment tool for laboratory services and supply chain (ATLAS), 2006. Of the 100 laboratories, 16 were referral laboratories (hubs). To assess human resource constraints, we conducted 100 key informant interviews with laboratory managers and in charges.

Results

Across the facilities, there was an excess number of laboratory technicians at Health Center (HC) IV level by 30% and laboratory assistants were in excess by 90%. There was a shortage of laboratory technologists with only 50% of the posts filled at general hospitals. About 87.5% of hub laboratories had conducted formal onsite training compared to 51.2% of the non-hub laboratories. Less than half of HC III laboratories had conducted a formal onsite training; hospital laboratories had not conducted training on the use and maintenance of equipment. Almost all HC III laboratories had been supervised though supervision focused on HIV/AIDS. Financial resources, workload and lack of supervision were major constraints to human resource strengthening.

Conclusion

Although opportunities for continuous education have emerged over the past decade, they are still threatened by inadequate staffing, skill mix and escalating workload. Moreover, excesses in staffing are more in favour of HIV, TB and malaria. The Ministry of Health needs to develop work-based staffing models to ensure adequate staff numbers and skill mix. Staffing norms need to be revised to accommodate laboratory technologists and scientists at high-level laboratories. Training needs to extend beyond HIV, TB and malaria.
Supporting the use of research evidence in decision-making in crisis zones in low- and middle-income countries: a critical interpretive synthesis
Authors: Khalid Ahmad Firas , Lavis John N. , El-Jardali Fadi , Vanstone Meredith
Published: February 2020

Background

Decision-makers in crisis zones are faced with the challenge of having to make health-related decisions under limited time and resource constraints and in light of the many factors that can influence their decisions, of which research evidence is just one. To address a key gap in the research literature about how best to support the use of research evidence in such situations, we conducted a critical interpretive synthesis approach to develop a conceptual framework that outlines the strategies that leverage the facilitators and address the barriers to evidence use in crisis zones.

Methods

We systematically reviewed both empirical and non-empirical literature and used an interpretive analytic approach to synthesise the results and develop the conceptual framework. We used a ‘compass’ question to create a detailed search strategy and conducted electronic searches in CINAHL, EMBASE, MEDLINE, SSCI and Web of Science. A second reviewer was assigned to a representative sample of articles. We purposively sampled additional papers to fill in conceptual gaps.

Results

We identified 21 eligible papers to be analysed and purposively sampled an additional 6 to fill conceptual gaps. The synthesis resulted in a conceptual framework that focuses on evidence use in crisis zones examined through the lens of four systems – political, health, international humanitarian aid and health research. Within each of the four systems, the framework identifies the most actionable strategies that leverage the facilitators and address the barriers to evidence use.

Conclusions

This study presents a new conceptual framework that outlines strategies that leverage the facilitators and address the barriers to evidence use in crisis zones within different systems. This study expands on the literature pertaining to evidence-informed decision-making.
Comprehensive analysis of the association between tumor glycolysis and immune/inflammation function in breast cancer
Authors: Li Wenhui , Xu Ming , Li Yu , Huang Ziwei , Zhou Jun , Zhao Qiuyang , Le Kehao , Dong Fang , Wan Cheng , Yi Pengfei
Published: February 2020

Background

Metabolic reprogramming, immune evasion and tumor-promoting inflammation are three hallmarks of cancer that provide new perspectives for understanding the biology of cancer. We aimed to figure out the relationship of tumor glycolysis and immune/inflammation function in the context of breast cancer, which is significant for deeper understanding of the biology, treatment and prognosis of breast cancer.

Methods

Using mRNA transcriptome data, tumor-infiltrating lymphocytes (TILs) maps based on digitized H&E-stained images and clinical information of breast cancer from The Cancer Genome Atlas projects (TCGA), we explored the expression and prognostic implications of glycolysis-related genes, as well as the enrichment scores and dual role of different immune/inflammation cells in the tumor microenvironment. The relationship between glycolysis activity and immune/inflammation function was studied by using the differential genes expression analysis, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analyses (GSEA) and correlation analysis.

Results

Most glycolysis-related genes had higher expression in breast cancer compared to normal tissue. Higher phosphoglycerate kinase 1 (PGK1) expression was associated with poor prognosis. High glycolysis group had upregulated immune/inflammation-related genes expression, upregulated immune/inflammation pathways especially IL-17 signaling pathway, higher enrichment of multiple immune/inflammation cells such as Th2 cells and macrophages. However, high glycolysis group was associated with lower infiltration of tumor-killing immune cells such as NKT cells and higher immune checkpoints expression such as PD-L1, CTLA4, FOXP3 and IDO1.

Conclusions

In conclusion, the enhanced glycolysis activity of breast cancer was associated with pro-tumor immunity. The interaction between tumor glycolysis and immune/inflammation function may be mediated through IL-17 signaling pathway.