bluuebunny/crossref_metadata_2025 huggingface dataset:
The NAD kinase OsNADK1 affects the intracellular redox balance and enhances the tolerance of rice to drought
Authors: Wang Xiang , Li Bin-Bin , Ma Tian-Tian , Sun Liang-Yu , Tai Li , Hu Chun-Hong , Liu Wen-Ting , Li Wen-Qiang , Chen Kun-Ming
Published: January 2020

Background

NAD kinases (NADKs) are the only known enzymes that directly phosphorylate NAD(H) to generate NADP(H) in different subcellular compartments. They participate in multiple life activities, such as modulating the NADP/NAD ratio, maintaining the intracellular redox balance and responding to environmental stresses. However, the functions of individual NADK in plants are still under investigation. Here, a rice NADK, namely, OsNADK1, was identified, and its functions in plant growth regulation and stress tolerance were analysed by employing a series of transgenic plant lines.

Results

OsNADK1 is a cytosol-localized NADK in rice. It was expressed in all rice tissues examined, and its transcriptional expression could be stimulated by a number of environmental stress treatments. Compared with wild-type (WT) rice, the mutant plant osnadk1 in which OsNADK1 was knocked out was a dwarf at the heading stage and had decreased NADP(H)/NAD(H), ascorbic acid (ASA)/dehydroascorbate (DHA) and reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios, which led to increased oxidation states in the rice cells and sensitivity to drought. Moreover, certain stress-related genes showed differential expression patterns in osnadk1 under both normal growth and drought-stress conditions compared with WT. Among these genes, OsDREB1B and several WRKY family transcription factors, e.g., OsWRKY21 and OsWRKY42, showed correlated co-expression patterns with OsNADK1 in osnadk1 and the plants overexpressing or underexpressing OsNADK1, implying roles for these transcription factors in OsNADK1-mediated processes. In addition, overexpression of OsNADK1 enhanced the drought tolerance of rice plants, whereas loss of function of the gene reduced the tolerance. Furthermore, the proline content was dramatically increased in the leaves of the OsNADK1-overexpressing lines under drought conditions.

Conclusions

Altogether, the results suggest that an OsNADK1-mediated intracellular redox balance is involved in the tolerance of rice plants to drought.
Supreme™ laryngeal mask airway insertion requires a lower concentration of sevoflurane than ProSeal™ laryngeal mask airway insertion during target-controlled remifentanil infusion: a prospective randomised controlled study
Authors: Monteserín-Matesanz Cristina , González Tatiana , Anadón-Baselga María José , Zaballos Matilde
Published: January 2020

Background

ProSeal (PLMA) and Supreme (SLMA) laryngeal mask airways are effective ventilator devices with distinctive designs that may require different anaesthetics for insertion. Sevoflurane induction provides acceptable conditions for laryngeal mask insertion, and remifentanil significantly decreases the minimum alveolar concentration of sevoflurane required for that insertion. The study aimed to evaluate the optimal end-tidal (ET) sevoflurane concentration for successful insertion of PLMA versus SLMA in patients receiving a remifentanil infusion without a neuromuscular blocking agent.

Methods

Altogether, 45 patients ASA (American Society Anaesthesiologists) physical status I–II, aged 18–60 years were scheduled for elective ambulatory surgery. Exclusion criteria were a difficult airway, recent respiratory infection, reactive airway, obstructive sleep apnoea syndrome, gastric aspiration’s risk factors, pregnancy, and lactation. Patients were randomly allocated to receive the SLMA or the PLMA. Sevoflurane induction with co-administration of remifentanil was performed at an effect-site concentration of 4 ng mL− 1. ET50 was calculated with a modified Dixon’s up-and-down method (starting at 2.5% in steps of 0.5%). Predetermined sevoflurane concentration was kept constant during the 10 min before LMA insertion. Patient’s response to LMA insertion was classified as “movement” or “no movement”. Sevoflurane ET50 was determined as the midpoint concentration of all the independent pairs that manifested crossover from “movement” to “no movement”.

Results

The ET50 sevoflurane concentration co-administered with remifentanil required for PLMA insertion was 1.20 ± 0.41% (95% confidence interval 0.76 to 1.63%). For SLMA insertion, it was 0.55 ± 0.38% (95% confidence interval 0.14 to 0.95%) (p = 0.019).

Conclusions

The end-tidal sevoflurane concentration with co-administered remifentanil required to allow insertion of the SLMA was 54% lower than that needed for inserting the PLMA.

Trial registration

Clinicaltrials.gov identifier: NCT03003377. Retrospectively registered. Date of registration: December 28, 2016.
A retrospective genomic analysis of drug-resistant strains of M. tuberculosis in a high-burden setting, with an emphasis on comparative diagnostics and reactivation and reinfection status
Authors: Wollenberg Kurt , Harris Michael , Gabrielian Andrei , Ciobanu Nelly , Chesov Dumitru , Long Alyssa , Taaffe Jessica , Hurt Darrell , Rosenthal Alex , Tartakovsky Michael , Crudu Valeriu
Published: January 2020

Background

Recurrence of drug-resistant tuberculosis (DR-TB) after treatment occurs through relapse of the initial infection or reinfection by a new drug-resistant strain. Outbreaks of DR-TB in high burden regions present unique challenges in determining recurrence status for effective disease management and treatment. In the Republic of Moldova the burden of DR-TB is exceptionally high, with many cases presenting as recurrent.

Methods

We performed a retrospective analysis of Mycobacterium tuberculosis from Moldova to better understand the genomic basis of drug resistance and its effect on the determination of recurrence status in a high DR-burden environment. To do this we analyzed genomes from 278 isolates collected from 189 patients, including 87 patients with longitudinal samples. These pathogen genomes were sequenced using Illumina technology, and SNP panels were generated for each sample for use in phylogenetic and network analysis. Discordance between genomic resistance profiles and clinical drug-resistance test results was examined in detail to assess the possibility of mixed infection.

Results

There were clusters of multiple patients with 10 or fewer differences among DR-TB samples, which is evidence of person-to-person transmission of DR-TB. Analysis of longitudinally collected isolates revealed that many infections exhibited little change over time, though 35 patients demonstrated reinfection by divergent (number of differences > 10) lineages. Additionally, several same-lineage sample pairs were found to be more divergent than expected for a relapsed infection. Network analysis of the H3/4.2.1 clade found very close relationships among 61 of these samples, making differentiation of reactivation and reinfection difficult. There was discordance between genomic profile and clinical drug sensitivity test results in twelve samples, and four of these had low level (but not statistically significant) variation at DR SNPs suggesting low-level mixed infections.

Conclusions

Whole-genome sequencing provided a detailed view of the genealogical structure of the DR-TB epidemic in Moldova, showing that reinfection may be more prevalent than currently recognized. We also found increased evidence of mixed infection, which could be more robustly characterized with deeper levels of genomic sequencing.
Study protocol of a randomized controlled trial of home-based computerized executive function training for children with cerebral palsy
Authors: García-Galant María , Blasco Montse , Reid Lee , Pannek Kerstin , Leiva David , Laporta-Hoyos Olga , Ballester-Plané Júlia , Miralbell Júlia , Caldú Xavi , Alonso Xènia , Toro-Tamargo Esther , Meléndez-Plumed Mar , Gimeno Francisca , Coronas Marc , Soro-Camats Emili , Boyd Roslyn , Pueyo Roser
Published: January 2020

Background

Cerebral palsy (CP) is frequently associated with specific cognitive impairments, such as executive dysfunction which are related to participation and quality of life (QOL). The proposed study will examine whether a computerized executive function (EF) training programme could provide superior benefits for executive functioning, participation, QOL and brain plasticity, as compared to usual care.

Methods

A single-blind randomized controlled trial (RCT) design will be performed. Thirty children with CP aged 8 to 12 years will participate in a home-based computerized multi-modal executive training programme (12 weeks, 5 days a week, 30 min a day training, total dose = 30 h). Thirty children with CP matched by age, sex, motor and intelligence quotient (IQ) will compose the waitlist group. Cognitive, behavioural, emotional, participation and QOL measures will be obtained at three time points: before, immediately after and 9 months after completing the training. Additionally, structural and functional (resting state) magnetic resonance images (MRI) will be obtained in a subsample of 15 children from each group. Outcomes between groups will be compared following standard principles for RCTs.

Discussion

The study will test whether the cognitive training programme exerts a positive effect not only on neuropsychological and daily functioning of children with CP but also on other measures such as participation and QOL. We will also use brain MRI to test brain functional and structural changes after the intervention.

If this on-line and home-based training programme proves effective, it could be a cost-effective intervention with short- and long-term effects on EF, participation or QOL in CP.

Trial registration

ClinicalTrials.gov: NCT04025749. Registered 19 July 2019. Retrospectively registered.
What predicts the proxy-reported health-related quality of life of adolescents with cerebral palsy in Bangladesh?
Authors: Power Rosalie , Galea Claire , Muhit Mohammad , Heanoy Eamin , Karim Tasneem , Badawi Nadia , Khandaker Gulam
Published: January 2020

Background

The health-related quality of life (HRQoL) of adolescents with CP in low and middle-income countries is often poor, as is the case in Bangladesh. This exploratory study examined what factors predict the proxy-reported HRQoL of adolescents with CP in rural Bangladesh, a typical low- and middle-income country (LMIC).

Methods

Adolescents with CP (10 to 18y) were identified using the Bangladesh Cerebral Palsy Register. HRQoL was assessed using the Cerebral Palsy Quality of Life-Teens proxy-report questionnaire (CPQoL-Teens), adolescent mental health using the Strengths and Difficulty Questionnaire (SDQ) and caregiver mental health using the Depression, Anxiety and Stress Scale (DASS-21). Theoretical and statistical interests (i.e. bivariate analysis, p < 0.05) identified potential predictors which were entered into hierarchical multiple linear regression (HMLR) models in order of clinical significance; HMLR related adolescent clinical characteristics, adolescent and caregiver mental health and proxies of socioeconomic status to CPQoL-Teens dimensions.

Results

One hundred fifty-four adolescents with CP (mean age 15y 1mo, SD 1y 8mo, female 31.2%) participated in this study.

Twenty-four factors were identified to explore for relationship to adolescent proxy-reported HRQoL. Fifteen of the factors correlated to one or more CPQoL-Teens dimension; strongest correlation was between ‘feelings about functioning’ and motor impairment (r = 0.545). Nine were predictive of CPQoL-Teens dimensions; adolescent sex, school attendance, severity of motor impairment, hearing and speech impairment, mother’s education, primary caregiver depression and stress, and having a sanitary latrine at home resulting in score changes of between 0.79 (95% CI 0.24 to 1.35) to 35.1 (95% CI 6.03 to 64.22).

Conclusions

Many of the factors predicting the proxy-reported HRQoL of adolescents with CP are amenable to intervention, and have the potential to improve adolescent wellbeing. Several determinants are priorities of the sustainable development goals (SDGs); these findings should inform resource prioritization to improve the wellbeing of adolescents with CP in Bangladesh and other LMICs.
Diagnostic accuracy of history taking, physical examination and imaging for phalangeal, metacarpal and carpal fractures: a systematic review update
Authors: Krastman Patrick , Mathijssen Nina M. , Bierma-Zeinstra Sita M. A. , Kraan Gerald , Runhaar Jos
Published: January 2020

Background

The standard diagnostic work-up for hand and wrist fractures consists of history taking, physical examination and imaging if needed, but the supporting evidence for this work-up is limited. The purpose of this study was to systematically examine the diagnostic accuracy of tests for hand and wrist fractures.

Methods

A systematic search for relevant studies was performed. Methodological quality was assessed and sensitivity (Se), specificity (Sp), accuracy, positive predictive value (PPV) and negative predictive value (NPV) were extracted from the eligible studies.

Results

Of the 35 eligible studies, two described the diagnostic accuracy of history taking for hand and wrist fractures. Physical examination with or without radiological examination for diagnosing scaphoid fractures (five studies) showed Se, Sp, accuracy, PPV and NPV ranging from 15 to 100%, 13–98%, 55–73%, 14–73% and 75–100%, respectively. Physical examination with radiological examination for diagnosing other carpal bone fractures (one study) showed a Se of 100%, with the exception of the triquetrum (75%). Physical examination for diagnosing phalangeal and metacarpal fractures (one study) showed Se, Sp, accuracy, PPV and NPV ranging from 26 to 55%, 13–89%, 45–76%, 41–77% and 63–75%, respectively.

Imaging modalities of scaphoid fractures showed predominantly low values for PPV and the highest values for Sp and NPV (24 studies). Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Ultrasonography (US) and Bone Scintigraphy (BS) were comparable in diagnostic accuracy for diagnosing a scaphoid fracture, with an accuracy ranging from 85 to 100%, 79–100%, 49–100% and 86–97%, respectively. Imaging for metacarpal and finger fractures showed Se, Sp, accuracy, PPV and NPV ranging from 73 to 100%, 78–100%, 70–100%, 79–100% and 70–100%, respectively.

Conclusions

Only two studies were found on the diagnostic accuracy of history taking for hand and wrist fractures in the current review. Physical examination was of moderate use for diagnosing a scaphoid fracture and of limited use for diagnosing phalangeal, metacarpal and remaining carpal fractures. MRI, CT and BS were found to be moderately accurate for the definitive diagnosis of clinically suspected carpal fractures.
A new lever reduction technique for the surgical treatment of elderly patients with lumbar degenerative Spondylolisthesis
Authors: Kong Chao , Wang Wei , Li Xiangyu , Sun Xiangyao , Ding Junzhe , Lu Shibao
Published: January 2020

Background

Proper reduction method for Lumbar degenerative spondylolisthesis (LDS) is still controversial. The aim of this study was to determine the safety and effectiveness of lever reduction combined with traditional elevating-pull reduction technique for the treatment of elderly patients with LDS.

Methods

From May 2015 to December 2017, 142 elderly patients (≥65 years) diagnosed with LDS were enrolled in this study with a mean follow-up of 25.42 ± 8.31 months. All patients were operated using lever reduction combined with traditional elevating-pull reduction technique. Patient age, sex, body mass index, bone mineral density, preoperative comorbidities, surgical duration, blood loss, and surgical complications were collected form patient charts. Clinical data as visual analog scale (VAS), Oswestry Disability Index (ODI), and 36-Item Short Form Health Survey (SF-36) were collected preoperatively, 1 month postoperatively, and at the final follow-up. Radiographic evaluation included slip percentage, slip angle (SA), lumbar lordosis (LL), and fusion status.

Results

The clinical parameters of VASback, VASleg, ODI, and SF-36 had significantly improved at both follow-ups after surgery. A significant improvement was indicated for slippage reduction at both follow-ups, showing no significant correction loss after surgery. SA significantly increased after surgery and was well maintained at the final follow-up. LL was not affected by the surgery. At the final follow-up, complete fusion was obtained in 121 patients (85.2%) and partial fusion in 21 (14.8%). Revision surgery was performed for one patient. Screw loosening was observed in 3 (2.11%) cases. No nerve root injury or adjacent segment disease was observed.

Conclusions

This new lever reduction combined with traditional elevating-pull reduction technique for the surgical treatment of elderly patients with LDS is both safe and effective. Satisfactory correction and fusion rates were achieved with acceptable correction loss and reduction-related complications.
Improving obesity management training in family medicine: multi-methods evaluation of the 5AsT-MD pilot course
Authors: Luig Thea , Wicklum Sonja , Heatherington Melanie , Vu Albert , Cameron Erin , Klein Doug , Sharma Arya M. , Campbell-Scherer Denise L.
Published: January 2020

Background

Quality, evidence-based obesity management training for family medicine residents is needed to better support patients. To address this gap, we developed a comprehensive course based on the 5As of Obesity Management™ (ASK, ASSESS, ADVISE, AGREE, ASSIST), a framework and suite of resources to improve residents’ knowledge and confidence in obesity counselling. This study assessed the course’s impact on residents’ attitudes, beliefs, and confidence with obesity counselling.

Methods

The course combines lectures with a bariatric empathy suit experience, standardized and in-clinic patient practice, and narrative reflections. Using a multi-methods design we measured changes in 42 residents’ attitudes, beliefs, and self-confidence and thematically analyzed the narrative reflections to understand residents’ experience with the course content and pedagogy.

Results

Following the course, residents reported improved attitudes towards people living with obesity and improved confidence for obesity counselling. Pre/post improvement in BAOP scores (n = 32) were significant (p < .001)., ATOP scores did not change significantly. Residents showed improvement in assessing root causes of weight gain (p < .01), advising patients on treatment options (p < .05), agreeing with patients on health outcomes (p < .05), assisting patients in addressing their barriers (p < .05), counseling patients on weight gain during pregnancy, (p < .05), counseling patients on depression and anxiety (p < .01), counseling patients on iatrogenic causes of weight gain (p < .01), counseling patients who have children with obesity (p < .05), and referring patients to interdisciplinary providers for care (p < .05).

Qualitative analysis of narrative reflections illustrates that experiential learning was crucial in increasing residents’ ability to empathically engage with patients and to critically reflect on implications for their practice.

Conclusion

The 5AsT-MD course has the potential to increase residents’ confidence and competency in obesity prevention and management. Findings reflect the utility of the 5As to improve residents’ confidence and competency in obesity management counselling.
Exploring the incidence of culturally responsive communication in Australian healthcare: the first rapid review on this concept
Authors: Minnican Carla , O’Toole Gjyn
Published: January 2020

Background

Increasing diversity in Australia requires healthcare practitioners to consider the cultural, linguistic, religious, sexual and racial/ethnic characteristics of service users as integral components of healthcare delivery. This highlights the need for culturally appropriate communication and care. Indeed the Australian Government in various policies mandates culturally responsive communication. Therefore this paper aims to provide a brief overview of Australian healthcare literature exploring the components; prevalence and effects of this style of communication in healthcare.

Methods

A rapid review was conducted using the knowledge to action evidence summary approach. Articles included in the review were those reporting on the components, prevalence and outcomes of culturally responsive communication in Australian healthcare, published in English between 2008 and 2018. Articles were reviewed using reliable critical appraisal procedures.

Results

Twenty- six articles were included in the final review (23 qualitative studies; 2 systematic reviews; 1 mixed methods study). The literature indicates knowledge of the positive effects of culturally responsive communication in healthcare. It also highlights the disparity between the perceptions of healthcare practitioners and services users over the existence and components of culturally responsive communication in healthcare. The review identified a limited use of this style of communication, but rather a focus on barriers to culturally appropriate care, lacking an awareness of the importance of culturally responsive communication in this care.

Conclusion

While literature suggests the importance and positive effects of culturally responsive communication, evidence suggests inconsistent implementation of this style of communication within Australian healthcare settings. This has implications for the outcomes of healthcare for the diverse population in Australia.
Mass cytometry analysis reveals a distinct immune environment in peritoneal fluid in endometriosis: a characterisation study
Authors: Guo Manman , Bafligil Cemsel , Tapmeier Thomas , Hubbard Carol , Manek Sanjiv , Shang Catherine , Martinez Fernando O. , Schmidt Nicole , Obendorf Maik , Hess-Stumpp Holger , Zollner Thomas M. , Kennedy Stephen , Becker Christian M. , Zondervan Krina T. , Cribbs Adam P. , Oppermann Udo
Published: January 2020

Background

Endometriosis is a gynaecological condition characterised by immune cell infiltration and distinct inflammatory signatures found in the peritoneal cavity. In this study, we aim to characterise the immune microenvironment in samples isolated from the peritoneal cavity in patients with endometriosis.

Methods

We applied mass cytometry (CyTOF), a recently developed multiparameter single-cell technique, in order to characterise and quantify the immune cells found in peritoneal fluid and peripheral blood from endometriosis and control patients.

Results

Our results demonstrate the presence of more than 40 different distinct immune cell types within the peritoneal cavity. This suggests that there is a complex and highly heterogeneous inflammatory microenvironment underpinning the pathology of endometriosis. Stratification by clinical disease stages reveals a dynamic spectrum of cell signatures suggesting that adaptations in the inflammatory system occur due to the severity of the disease. Notably, among the inflammatory microenvironment in peritoneal fluid (PF), the presence of CD69+T cell subsets is increased in endometriosis when compared to control patient samples. On these CD69+cells, the expression of markers associated with T cell function are reduced in PF samples compared to blood. Comparisons between CD69+and CD69−populations reveal distinct phenotypes across peritoneal T cell lineages. Taken together, our results suggest that both the innate and the adaptive immune system play roles in endometriosis.

Conclusions

This study provides a systematic characterisation of the specific immune environment in the peritoneal cavity and identifies cell immune signatures associated with endometriosis. Overall, our results provide novel insights into the specific cell phenotypes governing inflammation in patients with endometriosis. This prospective study offers a useful resource for understanding disease pathology and opportunities for identifying therapeutic targets.
Aspirin, clopidogrel and prasugrel monotherapy in patients with type 2 diabetes mellitus: a double-blind randomised controlled trial of the effects on thrombotic markers and microRNA levels
Authors: Parker William A. E. , Schulte Christian , Barwari Temo , Phoenix Fladia , Pearson Sam M. , Mayr Manuel , Grant Peter J. , Storey Robert F. , Ajjan Ramzi A.
Published: January 2020

Background

Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM.

Materials and methods

56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study. Platelet aggregation (PA) was determined by light-transmittance aggregometry and P-selectin expression by flow cytometry. Markers of fibrin clot dynamics, inflammation and coagulation were measured. Plasma levels of 14 miRNA were assessed by quantitative polymerase chain reactions.

Results

Of the 56 patients, 24 (43%) were receiving aspirin for primary prevention of ischaemic events and 32 (57%) for secondary prevention. Prasugrel was the strongest inhibitor of ADP-induced PA (mean ± SD maximum response to 20μmol/L ADP 77.6 ± 8.4% [aspirin] vs. 57.7 ± 17.6% [clopidogrel] vs. 34.1 ± 14.1% [prasugrel], p < 0.001), P-selectin expression (30 μmol/L ADP; 45.1 ± 21.4% vs. 27.1 ± 19.0% vs. 14.1 ± 14.9%, p < 0.001) and collagen-induced PA (2 μg/mL; 62.1 ± 19.4% vs. 72.3 ± 18.2% vs. 60.2 ± 18.5%, p < 0.001). Fibrin clot dynamics and levels of coagulation and inflammatory proteins were similar. Lower levels of miR-24 (p = 0.004), miR-191 (p = 0.019), miR-197 (p = 0.009) and miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs. aspirin. Circulating miR-197 was lower in those cardiovascular disease during therapy with aspirin (p = 0.039) or prasugrel (p = 0.0083).

Conclusions

Prasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated miRNAs. miR-197 is a potential marker of cardiovascular disease in this population. Clinical outcome studies investigating prasugrel monotherapy are warranted in individuals with T2DM.

Trial registration EudraCT, 2009-011907-22. Registered 15 March 2010, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB.
Silencing of AURKA augments the antitumor efficacy of the AURKA inhibitor MLN8237 on neuroblastoma cells
Authors: Yang Yan , Ding Lili , Zhou Qi , Fen Li , Cao Yuhua , Sun Junjie , Zhou Xuefeng , Liu Aiguo
Published: January 2020

Background

Aurora kinase A (AURKA) has been implicated in the regulation of cell cycle progression, mitosis and a key number of oncogenic signaling pathways in various malignancies including neuroblastoma. Small molecule inhibitors of AURKA have shown potential, but still not as good as expected effects in clinical trials. Little is known about this underlying mechanism. Here, we evaluated the inhibitory effects of AURKA inhibitor MLN8237 on neuroblastoma cells to understand the potential mechanisms responsible for tumor therapy.

Methods

MLN8237 treatment on neuroblastoma cell line IMR32 was done and in vivo inhibitory effects were investigated using tumor xenograft model. Cellular senescence was evaluated by senescence-associated β-gal Staining assay. Flow cytometry was used to tested cell cycle arrest and cell apoptosis. Senescence-associated signal pathways were detected by western blot. CD133 microbeads and microsphere formation were used to separate and enrich CD133+ cells. AURKA small interfering RNA transfection was carried to downregulate AURKA level. Finally, the combination of MLN8237 treatment with AURKA small interfering RNA transfection were adopted to evaluate the inhibitory effect on neuroblastoma cells.

Results

We demonstrate that MLN8237, an inhibitor of AURKA, induces the neuroblastoma cell line IMR32 into cellular senescence and G2/M cell phase arrest. Inactivation of AURKA results in MYCN destabilization and inhibits cell growth in vitro and in a mouse model. Although MLN8237 inhibits AURKA kinase activity, it has almost no inhibitory effect on the AURKA protein level. By contrast, MLN8237 treatment leads to abnormal high expression of AURKA in vitro and in vivo. Knockdown of AURKA reduces cell survival. The combination of MLN8237 with AURKA small interfering RNA results in more profound inhibitory effects on neuroblastoma cell growth. Moreover, MLN8237 treatment followed by AURKA siRNA forces senescent cells into apoptosis via suppression of the Akt/Stat3 pathway.

Conclusions

The effect of AURKA-targeted inhibition of tumor growth plays roles in both the inactivation of AURKA activity and the decrease in the AURKA protein expression level.
Identification of Plasmodium falciparum proteoforms from liver stage models
Authors: Winer Benjamin , Edgel Kimberly A. , Zou Xiaoyan , Sellau Julie , Hadiwidjojo Sri , Garver Lindsey S. , McDonough Christin E. , Kelleher Neil L. , Thomas Paul M. , Villasante Eileen , Ploss Alexander , Gerbasi Vincent R.
Published: January 2020

Background

Immunization with attenuated malaria sporozoites protects humans from experimental malaria challenge by mosquito bite. Protection in humans is strongly correlated with the production of T cells targeting a heterogeneous population of pre-erythrocyte antigen proteoforms, including liver stage antigens. Currently, few T cell epitopes derived fromPlasmodium falciparum, the major aetiologic agent of malaria in humans are known.

Methods

In this study both in vitro and in vivo malaria liver stage models were used to sequence host and pathogen proteoforms. Proteoforms from these diverse models were subjected to mild acid elution (of soluble forms), multi-dimensional fractionation, tandem mass spectrometry, and top-down bioinformatics analysis to identify proteoforms in their intact state.

Results

These results identify a group of host and malaria liver stage proteoforms that meet a 5% false discovery rate threshold.

Conclusions

This work provides proof-of-concept for the validity of this mass spectrometry/bioinformatic approach for future studies seeking to reveal malaria liver stage antigens towards vaccine development.
Indoor use of attractive toxic sugar bait in combination with long-lasting insecticidal net against pyrethroid-resistant Anopheles gambiae: an experimental hut trial in Mbé, central Côte d’Ivoire
Authors: Furnival-Adams Joanna E. C. , Camara Soromane , Rowland Mark , Koffi Alphonsine A. , Ahoua Alou Ludovic P. , Oumbouke Welbeck A. , N’Guessan Raphael
Published: January 2020

Background

Indoor attractive toxic sugar bait (ATSB) has potential as a supplementary vector-control and resistance-management tool, offering an alternative mode of insecticide delivery to current core vector-control interventions, with potential to deliver novel insecticides. Given the high long-lasting insecticidal bed net (LLIN) coverage across Africa, it is crucial that the efficacy of indoor ATSB in combination with LLINs is established before it is considered for wider use in public health.

Methods

An experimental hut trial to evaluate the efficacy of indoor ATSB traps treated with 4% boric acid (BA ATSB) or 1% chlorfenapyr (CFP ATSB) in combination with untreated nets or LLINs (holed or intact), took place at the M’bé field station in central Côte d’Ivoire against pyrethroid resistant Anopheles gambiae sensu lato.

Results

The addition of ATSB to LLINs increased the mortality rates of wild pyrethroid-resistant An. gambiae from 19% with LLIN alone to 28% with added BA ATSB and to 39% with added CFP ATSB (p < 0.001). Anopheles gambiae mortality with combined ATSB and untreated net was similar to that of combined ATSB and LLIN regardless of which insecticide was used in the ATSB. The presence of holes in the LLIN did not significantly affect ATSB-induced An. gambiae mortality. Comparative tests against pyrethroid resistant and susceptible strains using oral application of ATSB treated with pyrethroid demonstrated 66% higher survival rate among pyrethroid-resistant mosquitoes.

Conclusion

Indoor ATSB traps in combination with LLINs enhanced the control of pyrethroid-resistant An. gambiae. However, many host-seeking An. gambiae entering experimental huts with indoor ATSB exited into the verandah trap without sugar feeding when restricted from a host by a LLIN. Although ATSB has potential for making effective use of classes of insecticide otherwise unsuited to vector control, it does not exempt potential selection of resistance via this route.
Delay in decision and determinants for safe abortion among women at health facilities in south West Ethiopia: facility based cross sectional study
Authors: Mizana Biru Abdissa , Woyecha Tsige , Abdu Samuel
Published: January 2020

Background

Delayed safe abortion is the most common cause of gynecologic admission in developing countries. The study, therefore, assessed the delay decision for safe abortion and determinant factors among women at health facilities in South West Ethiopia.

Methods

Facility-based cross-sectional study was conducted among 384 women who were selected from health facilities by using simple random sampling. A pre-tested structured questionnaire was used for data collection. Data were entered into Epidata and exported to SPSS for analysis. Binary Logistic regression was used and Variables with P-value < 0.25 during bivariate analysis were included in the multivariable logistic regression model. Finally, variables with p-value ≤0.05 were judged as a statistically significant association.

Results

The magnitude of delay decision for safe abortion services was 70.8% (0.66, 075). Place of residence [AOR 2.44 (95% C.I: (1.39, 4.30)], lack of formal education [AOR: 2.41 (95% C.I:(1.08, 3.59)], level of education [AOR: 2.22 (95% C.I: (1.19, 4.11)], history of previous abortion [AOR: 3.47 (95% C.I: (1.74, 8.6.91)] and late confirmation of pregnancy [AOR: 1.64 (95% C.I: (1.01–2.65)] were the determinant factors for delay in decision for safe abortion.

Conclusion

This study revealed that the majority of women were delayed for the decision of safe abortion services. Place of residence of the women, lack of formal education, history of previous abortion and late confirmation of pregnancy were the determinant factors for women’s decision for safe abortion. Therefore, it is better to work on awareness creation the timing of safe abortion and complication of delay abortion especially for the women from rural area.
The Persian short form Aging Perceptions Questionnaire (APQ-P): A validation study
Authors: Miremadi Mojgan , Bandari Razieh , Heravi-Karimooi Majideh , Rejeh Nahid , Sharif Nia Hamid , Montazeri Ali
Published: January 2020

Background

Population aging is an important phenomenon for many countries worldwide. Considering the growing trend of aging population in Iran, it is very important to consider beliefs and perceptions of old people about aging. The Aging Perception Questionnaire (APQ) is one of the most common instruments that used to measure aging comprehension. The present study was a methodological inquiry that aimed to examine validity and reliability of the Persian version of the Aging Perception Questionnaire (APQ).

Methods

Forward-backward procedure was used for translation. Content validity and face validity were evaluated qualitatively. In order to evaluate construct validity a cross section study was conducted and both exploratory and confirmatory factor analyses were performed. In order to determine reliability, internal consistency (the Cronbach’s alpha) and stability (Intraclass Correlation Coefficient -ICC) were estimated.

Results

A total of 500 elderly people attending the community centers in Tehran, Iran were entered in other study and completed the Persian version of the questionnaire. Most elderly were female (52.8%).The mean age of participants was 68.33 (SD ± 6.10) years. The results obtained from exploratory factor analysis showed a four-factors solution (consequences negative, emotional representation, control positive and consequences positive) that jointly explained 52.8% of the total variance observed. In addition the confirmatory factory analysis showed a good fit for the data. Finally, the Cronbach’s alpha coefficient of 0.83 ranging from 0.80 to 0.87 was obtained for the whole scale and the subscales. The ICC value of 0.96 ranging from 0.90 to 0.98 was found for the whole scale and the subscales.

Conclusion

The results indicated that the Persian version of APQ is valid and can be used to measure aging perception in Iran.
Psychometric properties of the Danish Hospital Anxiety and Depression Scale in patients with cardiac disease: results from the DenHeart survey
Authors: Christensen Anne Vinggaard , Dixon Jane K. , Juel Knud , Ekholm Ola , Rasmussen Trine Bernholdt , Borregaard Britt , Mols Rikke Elmose , Thrysøe Lars , Thorup Charlotte Brun , Berg Selina Kikkenborg
Published: January 2020

Background

Anxiety and depression symptoms are common among cardiac patients. The Hospital Anxiety and Depression Scale (HADS) is frequently used to measure symptoms of anxiety and depression; however, no study on the validity and reliability of the scale in Danish cardiac patients has been done. The aim, therefore, was to evaluate the psychometric properties of HADS in a large sample of Danish patients with the four most common cardiac diagnoses: ischemic heart disease, arrhythmias, heart failure and heart valve disease.

Methods

The DenHeart study was designed as a national cross-sectional survey including the HADS, SF-12 and HeartQoL and combined with data from national registers. Psychometric evaluation included analyses of floor and ceiling effects, structural validity using both exploratory and confirmatory factor analysis and hypotheses testing of convergent and divergent validity by relating the HADS scores to the SF-12 and HeartQoL. Internal consistency reliability was evaluated by Cronbach’s alpha, and differential item functioning by gender was examined using ordinal logistic regression.

Results

A total of 12,806 patients (response rate 51%) answered the HADS. Exploratory factor analysis supported the original two-factor structure of the HADS, while confirmatory factor analysis supported a three-factor structure consisting of the original depression subscale and two anxiety subscales as suggested in a previous study. There were floor effects on all items and ceiling effect on item 8. The hypotheses regarding convergent validity were confirmed but those regarding divergent validity for HADS-D were not. Internal consistency was good with a Cronbach’s alpha of 0.87 for HADS-A and 0.82 for HADS-D. There were no indications of noticeable differential item functioning by gender for any items.

Conclusions

The present study supported the evidence of convergent validity and high internal consistency for both HADS outcomes in a large sample of Danish patients with cardiac disease. There are, however, conflicting results regarding the factor structure of the scale consistent with previous research.

Trial registration

ClinicalTrials.gov: NCT01926145.
Neuropsychiatric outcomes before and after switching to dolutegravir-based therapy in an acute HIV cohort
Authors:   the RV254/SEARCH 010 Research Team, Chan Phillip , Goh Orlanda , Kroon Eugène , Colby Donn , Sacdalan Carlo , Pinyakorn Suteeraporn , Prueksakaew Peeriya , Reiss Peter , Ananworanich Jintanat , Valcour Victor , Spudich Serena , Paul Robert
Published: January 2020

Introduction

Dolutegravir (DTG)-based antiretroviral therapy (ART) is currently the first-line treatment for people living with HIV. Neuropsychiatric adverse events (NP-AEs) have been reported with DTG but neuropsychiatric symptoms have not been systemically quantified using structured scales. This study examined mood and cognitive parameters before and after a planned transition from non-DTG to DTG-based ART within a longitudinal study of acute HIV infection (AHI).

Methods

RV254 AHI cohort participants on ≥ 24 weeks of ART initiated at AHI underwent sequential assessments before and after the switch including: (1) Patient Health Questionnaire-9 (PHQ-9), a 9-item survey (scores 0–27) that evaluates somatic and affective/cognitive symptoms of depression; (2) a 2-Questions screening that has been validated locally for depression; (3) Distress Thermometer (scores 0–10); and 4) administration of a 4-test neurocognitive battery sensitive to HIV.

Results

254 individuals (95% male, median age 30) switched to a DTG-based regimen after a median 144 weeks of ART. Serial assessments were completed at a median of 19 weeks before and 37 weeks after DTG. There was a modest but statistically significant increase in PHQ-9 scores after DTG (pre-switch: 5 [IQR 1–7] vs. Post-switch: 5 [IQR 2–8], p = 0.009). The percentage of participants with at least moderate depression (PHQ-9 ≥ 10) increased from 10 to 16% (p = 0.006), but the frequency of moderate-severe depression (PHQ-9 ≥ 15) remained unchanged (3%). No volunteer reported NP-AEs within the study period. Somatic symptoms of depression increased more than cognitive/affective symptoms. Plasma viral suppression (HIV-1 RNA < 50; p = 0.005) and PHQ-9 ≥ 10 (p < 0.001) before switch were linked to lower PHQ-9 scores after DTG in multivariable analysis. Performance on all neuropsychological tests, except grooved pegboard test, improved modestly after DTG (all p < 0.05).

Conclusion

After a median duration of 37 weeks of DTG use, there was a modest increase in the higher quartile of PHQ-9. This increase was associated with a rise in moderate depression symptoms but not the more severe forms of depression on PHQ-9. No clinically relevant NP-AEs were reported. Pre-existing depression was not associated with subsequent worsening of symptoms after DTG. Cognitive test performance improved post-DTG but could be due to practice effect.
Functional properties of beetroot (Beta vulgaris) in management of cardio-metabolic diseases
Authors: Mirmiran Parvin , Houshialsadat Zeinab , Gaeini Zahra , Bahadoran Zahra , Azizi Fereidoun
Published: January 2020

Red beetroot (Beta vulgaris), as a naturally occurring root vegetable and a rich source of phytochemicals and bioactive compounds, is known for its beneficial roles in the improvement of several clinical and pathologic outcome. Chronic and acute beetroot juice supplementation, as a cost-effective strategy, is proposed to hold promises in controlling diabetes and insulin hemostasis, blood pressure and vascular function, renal health and the possible effect on microbiome abundance. The secondary outcome and physiological response of microbiome abundance modulation included the non- significant fluctuation of systolic and diastolic blood pressures. Also, some studies have suggested a reno-protective property of beetroot juice that is associated with the reduction of mortality rate and favorable changes in kidney’s functional parameters among patients with renal disorders. Similarly, it is shown that the persistent consumption of beetroot juice effectively postpones the postprandial glycemic response and decreases the blood glucose peak. The significant blood pressure lowering effect has been seen among normotensive subjects, which tend to be more considerable among hypertensive individuals and progressive among overweight adults.

Within this context, this review aims to provide a comprehensive overview on the therapeutic applications of beetroot juice in metabolic disorders and theirs underlying mechanisms. Despite the inconsistencies in the set of results from the reviewed studies, there is no doubt that further contributing factors must be investigated more deeply in future studies.
Prevalence and root causes of surgical site infections at an academic trauma and burn center in Ethiopia: a cross-sectional study
Authors: Mezemir Rahel , Seid Awole , Gishu Teshome , Demas Tangut , Gize Addisu
Published: January 2020

Background

Despite modern surgical techniques and the use of antibiotic prophylaxis, surgical site infection remains a burden for the patient and health system. It is a major cause of morbidity, prolonged hospital stay, and increased health costs. Thus, the main aim of this study was to determine the prevalence and root causes of surgical site infection among patients undergoing major surgery at an academic trauma and burn center in Ethiopia.

Methods

A hospital based cross-sectional study was conducted on 249 patients during 6-months’ time window. Data entered in SPSS and multivariate logistic regression was employed to determine the root causes and the outcome variable.

Results

The prevalence of surgical site infection was found to be 24.6% of whom 10% develop deep site, 9.2% organ spaced and the remaining 5.2% develop superficial space surgical site infection. The prevalence was high in patients who had undergone orthopedics (54.3%) and abdominal (30%) surgeries. Educational status, pre-morbid illness, duration of pre-operative and post-operative hospital stay, ASA score, and type of the wound were significantly associated with SSI atp-value of ≤0.05. However, no association was found with BMI and location of the wound.

Conclusions

The prevalence of surgical site infection in the study population is still high. Preoperative hospital stay, pre-morbid illness, pre-operative and post-operative hospital stay, ASA score, and type of the wound were the independent predictors of surgical site infection. The duration of pre and post-operative periods should be kept to a minimum as much as possible. Patients with pre-morbid history of chronic diseases and contaminated wound require special attention to decrease the rate of occurrence of infections. In addition, longitudinal studies should be carried out to identify more risk factors.
Clustered CTCF binding is an evolutionary mechanism to maintain topologically associating domains
Authors: Kentepozidou Elissavet , Aitken Sarah J. , Feig Christine , Stefflova Klara , Ibarra-Soria Ximena , Odom Duncan T. , Roller Maša , Flicek Paul
Published: January 2020

Background

CTCF binding contributes to the establishment of a higher-order genome structure by demarcating the boundaries of large-scale topologically associating domains (TADs). However, despite the importance and conservation of TADs, the role of CTCF binding in their evolution and stability remains elusive.

Results

We carry out an experimental and computational study that exploits the natural genetic variation across five closely related species to assess how CTCF binding patterns stably fixed by evolution in each species contribute to the establishment and evolutionary dynamics of TAD boundaries. We perform CTCF ChIP-seq in multiple mouse species to create genome-wide binding profiles and associate them with TAD boundaries. Our analyses reveal that CTCF binding is maintained at TAD boundaries by a balance of selective constraints and dynamic evolutionary processes. Regardless of their conservation across species, CTCF binding sites at TAD boundaries are subject to stronger sequence and functional constraints compared to other CTCF sites. TAD boundaries frequently harbor dynamically evolving clusters containing both evolutionarily old and young CTCF sites as a result of the repeated acquisition of new species-specific sites close to conserved ones. The overwhelming majority of clustered CTCF sites colocalize with cohesin and are significantly closer to gene transcription start sites than nonclustered CTCF sites, suggesting that CTCF clusters particularly contribute to cohesin stabilization and transcriptional regulation.

Conclusions

Dynamic conservation of CTCF site clusters is an apparently important feature of CTCF binding evolution that is critical to the functional stability of a higher-order chromatin structure.