bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide analysis and expression profile of the bZIP gene family in poplar
Authors: Zhao Kai , Chen Song , Yao Wenjing , Cheng Zihan , Zhou Boru , Jiang Tingbo
Published: March 2021

Background

The bZIP gene family, which is widely present in plants, participates in varied biological processes including growth and development and stress responses. How do the genes regulate such biological processes? Systems biology is powerful for mechanistic understanding of gene functions. However, such studies have not yet been reported in poplar.

Results

In this study, we identified 86 poplar bZIP transcription factors and described their conserved domains. According to the results of phylogenetic tree, we divided these members into 12 groups with specific gene structures and motif compositions. The corresponding genes that harbor a large number of segmental duplication events are unevenly distributed on the 17 poplar chromosomes. In addition, we further examined collinearity between these genes and the related genes from six other species. Evidence from transcriptomic data indicated that the bZIP genes in poplar displayed different expression patterns in roots, stems, and leaves. Furthermore, we identified 45 bZIP genes that respond to salt stress in the three tissues. We performed co-expression analysis on the representative genes, followed by gene set enrichment analysis. The results demonstrated that tissue differentially expressed genes, especially the co-expressing genes, are mainly involved in secondary metabolic and secondary metabolite biosynthetic processes. However, salt stress responsive genes and their co-expressing genes mainly participate in the regulation of metal ion transport, and methionine biosynthetic.

Conclusions

Using comparative genomics and systems biology approaches, we, for the first time, systematically explore the structures and functions of the bZIP gene family in poplar. It appears that the bZIP gene family plays significant roles in regulation of poplar development and growth and salt stress responses through differential gene networks or biological processes. These findings provide the foundation for genetic breeding by engineering target regulators and corresponding gene networks into poplar lines.
Effects of dexmedetomidine on intraoperative hemodynamics, recovery profile and postoperative pain in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial
Authors: Ye Qin , Wang Fangjun , Xu Hongchun , Wu Le , Gao Xiaopei
Published: March 2021

Background

To investigate the optimal dose of dexmedetomidine to maintain hemodynamic stability, prevent of cough and minimize postoperative pain for patients undergoing laparoscopic cholecystectomy.

Methods

One hundred twenty patients were randomly divided into D1, D2, D3 and NS groups, and dexmedetomidine 0.4, 0.6, 0.8μg/kg and normal saline were administrated respectively. Patients’ heart rate, systolic blood pressure and diastolic blood pressure were measured at T1-T7. The incidence of cough was recorded. Other parameters were noted, the time of spontaneous respiratory recovery and extubation, visual analogue scale scores and dosage of tramadol.

Results

The heart rate, systolic blood pressure and diastolic blood pressure of D2 and D3 groups has smaller fluctuations at T2–3 and T7 compared with NS and D1 groups (P < 0.05). The incidence of cough was lower in D2 and D3 groups than NS group (P < 0.05). The visual analogue scale scores and tramadol dosage of D2 and D3 groups were lower than NS group (P < 0.05). The time of spontaneous respiratory recovery and extubation in D3 group was longer than that in D1 and D2 groups (P < 0.05).

Conclusions

Intravenous infusion of 0.6μg/kg dexmedetomidine before induction can maintain hemodynamic stability, decrease cough during emergence, relieve postoperative pain of patients undergoing laparoscopic cholecystectomy.

Trial registration

ChiCTR1900024801, registered at the Chinese Clinical Trial Registry, principal investigator: Qin Ye, date of registration: July 28, 2019.
Consistency and applicability of different brief screen instrument of cognitive function in elderly population
Authors: Lu Lixia , Chen Lin , Wu Weiwen , Wang Yang , Liu Zhenbao , Xu Jun , Yang Qianhong , Zhao Jun , Liu Liangxian , Yu Hui
Published: March 2021

Background

Screening for cognitive impairment (CI) is often hampered by lack of consensus as to which screening instrument to use. The aim is to assess the consistence and applicability of different CI screening tools.

Method

In a cross-sectional study from October 2017 to September 2018 in 7 communities in Shanghai, China, elder (≧60) residential volunteers with no history of major cardiovascular diseases, cancers and other comorbidities known to affect cognitive functions were recruited. The participants underwent tests with 7 cognitive function screening instruments. Multivariate linear regressions were performed to test correlations between demographic characteristics, including gender, age, education, and marital status, with cognitive test scores. Mini-Mental State Examination (MMSE) score adjusted according to the correlation coefficients was used to detect CI with a cutoff of 24. Other cognitive function scores were compared between participants with and without CI. In addition, Pearson’s correlation test was used to detect association between different test scores.

Results

172 participants with relatively low education levels were included. Age and education showed significant association with cognitive test scores. Using adjusted MMSE, 39.6% of participants were identified with CI, while the percentage was 87.2% when adjusted Montreal Cognitive Assessment (MoCA) with cutoff of 26 was used. Analysis of “abnormal” test scores showed that MMSE had the highest percentage of valid data (98.8%). MoCA and Isaacs test of Verbal Fluency (VF) score had correlation with most the other scores, while MMSE only significantly associated with VF and MoCA.

Conclusions

MMSE may still present the most applicable tools for quick screen of cognitive functions, especially when environmental conditions may interfere with participants’ attention.
ETV4 plays a role on the primary events during the adenoma-adenocarcinoma progression in colorectal cancer
Authors: Fonseca Aline Simoneti , Ramão Anelisa , Bürger Matheus Carvalho , de Souza Jorge Estefano Santana , Zanette Dalila Lucíola , de Molfetta Greice Andreotti , de Araújo Luiza Ferreira , de Barros e Lima Bueno Rafaela , Aguiar Graziela Moura , Plaça Jessica Rodrigues , Alves Cleidson de Pádua , dos Santos Anemari Ramos Dinarte , Vidal Daniel Onofre , Silva Gyl Eanes Barros , Panepucci Rodrigo Alexandre , Peria Fernanda Maris , Feres Omar , da Rocha José Joaquim Ribeiro , Zago Marco Antonio , Silva Wilson Araújo
Published: March 2021

Background

Colorectal cancer (CRC) is one of the most common cancers worldwide; it is the fourth leading cause of death in the world and the third in Brazil. Mutations in theAPC, DCC, KRASandTP53genes have been associated with the progression of sporadic CRC, occurring at defined pathological stages of the tumor progression and consequently modulating several genes in the corresponding signaling pathways. Therefore, the identification of gene signatures that occur at each stage during the CRC progression is critical and can present an impact on the diagnosis and prognosis of the patient. In this study, our main goal was to determine these signatures, by evaluating the gene expression of paired colorectal adenoma and adenocarcinoma samples to identify novel genetic markers in association to the adenoma-adenocarcinoma stage transition.

Methods

Ten paired adenoma and adenocarcinoma colorectal samples were subjected to microarray gene expression analysis. In addition, mutations inAPC, KRASandTP53genes were investigated by DNA sequencing in paired samples of adenoma, adenocarcinoma, normal tissue, and peripheral blood from ten patients.

Results

Gene expression analysis revealed a signature of 689 differentially expressed genes (DEG) (fold-change> 2,p< 0.05), between the adenoma and adenocarcinoma paired samples analyzed. Gene pathway analysis using the 689 DEG identified important cancer pathways such as remodeling of the extracellular matrix and epithelial-mesenchymal transition. Among these DEG, theETV4stood out as one of the most expressed in the adenocarcinoma samples, further confirmed in the adenocarcinoma set of samples from the TCGA database. Subsequent in vitro siRNA assays againstETV4resulted in the decrease of cell proliferation, colony formation and cell migration in the HT29 and SW480 colorectal cell lines. DNA sequencing analysis revealedKRASandTP53gene pathogenic mutations, exclusively in the adenocarcinomas samples.

Conclusion

Our study identified a set of genes with high potential to be used as biomarkers in CRC, with a special emphasis on theETV4gene, which demonstrated involvement in proliferation and migration.
Toward developing a metastatic breast cancer treatment strategy that incorporates history of response to previous treatments
Authors: Olow Aleksandra K. , Veer Laura van ’t , Wolf Denise M.
Published: March 2021

Background

Information regarding response to past treatments may provide clues concerning the classes of drugs most or least likely to work for a particular metastatic or neoadjuvant early stage breast cancer patient. However, currently there is no systematized knowledge base that would support clinical treatment decision-making that takes response history into account.

Methods

To model history-dependent response data we leveraged a published in vitro breast cancer viability dataset (84 cell lines, 90 therapeutic compounds) to calculate the odds ratios (log (OR)) of responding to each drug given knowledge of (intrinsic/prior) response to all other agents. This OR matrix assumes (1) response is based on intrinsic rather than acquired characteristics, and (2) intrinsic sensitivity remains unchanged at the time of the next decision point. Fisher’s exact test is used to identify predictive pairs and groups of agents (BH p < 0.05). Recommendation systems are used to make further drug recommendations based on past ‘history’ of response.

Results

Of the 90 compounds, 57 have sensitivity profiles significantly associated with those of at least one other agent, mostly targeted drugs. Nearly all associations are positive, with (intrinsic/prior) sensitivity to one agent predicting sensitivity to others in the same or a related class (OR > 1). In vitro conditional response patterns clustered compounds into five predictive classes: (1) DNA damaging agents, (2) Aurora A kinase and cell cycle checkpoint inhibitors; (3) microtubule poisons; (4) HER2/EGFR inhibitors; and (5) PIK3C catalytic subunit inhibitors. The apriori algorithm implementation made further predictions including a directional association between resistance to HER2 inhibition and sensitivity to proteasome inhibitors.

Conclusions

Investigating drug sensitivity conditioned on observed sensitivity or resistance to prior drugs may be pivotal in informing clinicians deciding on the next line of breast cancer treatments for patients who have progressed on their current treatment. This study supports a strategy of treating patients with different agents in the same class where an associated sensitivity was observed, likely after one or more intervening treatments.
Axial length of cataract eyes: a comparison of two cohorts over a span of 10 years apart
Authors: Hsiao Yu-Ting , Fang Po-Chiung , Wu Pei-Chang , Kuo Ming-Tse , Chen Yi-Hao , Kuo Hsi-Kung
Published: March 2021

Background

To assess the associations of axial length with age-related cataract within a span of 10 years in an Asian population in southern Taiwan.

Methods

A retrospective cohort study examined 960 adults who underwent cataract surgery at the Kaohsiung Chang Gung Memorial Hospital in year 2008 and year 2018. Axial length was assessed with the ultrasound biometry and/or the Zeiss IOLMaster. Eyes with prior blunt eye trauma or had underwent vitrectomy operations were excluded. The significance of the changes in axial length between the two cohorts was determined after performing age-matched analyses. Due to utilization of ultrasound biometry and/or Zeiss IOLMaster, axial length corrections with our mean difference in measurement results, which were similar to previous studies on comparison between the two measurement tools, were carried out.

Results

Axial length showed an age-related elongation in 10-year cross-sectional data, from a mean of 23.65 ± 1.80 mm in year 2008 to a mean of 24.30 ± 1.90 in year 2018 (p = 0.003). Patients with high myopia (axial length > 26 mm) increased significantly over the 10-year period from 8.1 to 16 % (p < 0.001). A birth cohort effect on axial length was evident as the axial lengths of year 2008 cohort were shorter than the 2018 cohort when they were in the same operation age group. In particular, persons born after the 1960s demonstrated a predominant increase in axial length in both cohorts.

Conclusions

Our study confirms a trend in increase of axial myopia, especially high myopias, over the 10-year period. A novel finding of this study was discovering a birth cohort effect on axial length, especially in persons born after the 1960s in southern Taiwan.
Ocular and corneal aberrations changes in controlled randomized clinical trial MiSight® Assessment Study Spain (MASS)
Authors: Lopes-Ferreira Daniela , Ruiz-Pomeda Alicia , Peréz-Sanchéz Belén , Queirós António , Villa-Collar César
Published: March 2021

Background

To compare ocular and corneal inherent aberrations in the naked eyes of randomly selected children fitted with MiSight contact lenses (CL) for myopia control, versus children corrected with single-vision spectacles (control), over a 24-months period.

Methods

Children aged 8 to 12 years, with myopia (-0.75 to -4.00 D sphere) and astigmatism (< -1.00 D cylinder) were randomly assigned to the lens study group (MiSight) or the control group (single-vision spectacles). The root mean square aberration (RMS) was determined as corneal (RMS_C), corneal high order RMS (HO_RMS_C), corneal low order RMS (LO_RMS_C), ocular (total) RMS (RMS_T), ocular high order RMS (HO_RMS_T), ocular low order RMS (LO_RMS_T), corneal spherical aberration (SA_C) and ocular SA (SA_T) were calculated by aberrometry measures at the baseline, on 12-months and 24-months visits. A 5 mm diameter was defined for the analysis in all visits for all subjects. Only the dominant eye was analyzed.

Results

Seventy-four subjects completed the clinical trial: 41 subjects from the MiSight group (age: 11.01 ± 1.23 years) and 33 from the single-vision group (age: 10.12 ± 1.38 years). RMS_T significantly changed (0.57 ± 0.20 µm, p = 0.029) after 24-months in the control group. In the MiSight group no significant changes were registered (p > 0.05). The SA_C and SA_T did not reveal significant changes between visits or between groups (p > 0.05).

Conclusions

Along 2 years, MiSight CL did not induce significant changes in RMS of anterior cornea or total ocular RMS. Contrary, in control group the RMS_T significantly changed as response of greater eye growth and myopia progression. The results obtained in present study allow to predict corneal or total aberration changes, in children, in response of wearing of MiSight lens along the time.

Trial registration

: ClinicalTrials.gov Identifier: NCT01917110.
Effect of the time interval between cataract surgery for both eyes on mental health outcome: a cohort study of 585,422 patients
Authors: Hou Chiun-Ho , Chen Ken-Jen , Lee Jiahn-Shing , Lin Ken-Kuo , Pu Christy
Published: March 2021

Background

Cataract surgeries can improve mental health outcomes. However, previous studies have not investigated whether the time interval between cataract surgeries for 2 eyes affects mental health outcomes.

Methods

We used the whole-population National Health Insurance (NHI) claims data from Taiwan to conduct a cohort study. Patients who received cataract surgeries for both eyes were identified (n = 585,422). The mental health inpatient and outpatient consultations received by these patients were analyzed, with different time intervals (< 3, 3 to 6, 6 to 12, and > 12 months) between the surgeries. Negative binominal regression was performed to estimate the interaction of the first eye surgery with the time interval.

Results

The number of mental health consultations was lowest among patients with a time interval of < 3 months (1.783–1.743, P < .001), and a negative dose response effect was observed, such that a longer time interval corresponded to a lower reduction in the number of mental health consultations. For patients with a time interval of > 12 months, the predicted number of mental health consultations increased from 1.674 to 1.796 (P < .001).

Conclusions

Given a patient expected to receive surgeries for both eyes within 1 year, scheduling both surgeries within a short time interval may be beneficial for maximizing the effects of cataract surgery in reducing the number of mental health consultations.
Adapting the Wheelchair Skills Program for pediatric rehabilitation: recommendations from key stakeholders
Authors: Daoust Geneviève , Rushton Paula W. , Racine Marissa , Leduc Karolann , Assila Najoua , Demers Louise
Published: March 2021

Background

Backed by over 20 years of research development, the Wheelchair Skills Program (WSP) has proven to be a safe and effective program to improving wheelchair skills for adult wheelchair users. However, evidence is lacking for the pediatric population, which may help to explain the limited use of the WSP in pediatric settings. While additional evidence specific to the pediatric population is needed, concurrent implementation of the WSP into pediatric clinical practice is equally prudent to allow those users to benefit from the years of accumulated WSP evidence. To facilitate implementation of evidence-based programs into practice, adaptation is also often required to improve the fit between the program and the local context. Therefore, the objective of this study was to understand what adaptations, if any, are required for the WSP to be implementable in a pediatric setting.

Methods

A deductive qualitative descriptive study design was used, guided by the Knowledge to Action Framework and Consolidated Framework for Implementation Research (CFIR). Occupational Therapists (OTs) from a pediatric rehabilitation center and two specialized schools in Montreal, Canada were invited to participate in a 90-min focus group. The Framework Method was followed for the data analysis.

Results

One focus group in each site (n = 3) was conducted with a total of 19 participants. From the OTs’ perspectives, our analysis revealed benefits of WSP use and various issues (e.g. some skills seem unrealistic) affecting its uptake in relation to the constructs of the CFIR Intervention Characteristics domain. The results provided guidance for the recommendations of adaptations (e.g. addition of a caregiver assistance score) to enhance implementation of the WSP in pediatric rehabilitation settings and helped to identify the need for the production of new knowledge and knowledge translation (KT) tools.

Conclusions

Implementation of the WSP with the adaptations and KT tools proposed could allow pediatric manual wheelchair users to improve their wheelchair skills.
Physical ACTivity in Survivorship (PACTS): study protocol for a randomized controlled trial evaluating a goal-directed therapeutic exercise program in pediatric posterior fossa brain tumor survivors
Authors: Kohler Brooke E. , Baque Emmah , Sandler Carolina X. , Brookes Denise S. K. , Terranova Caroline O. , Rixon Matthew , Hassall Tim , Trost Stewart G.
Published: March 2021

Background

Posterior fossa brain tumors (PFBT) are the most common solid tumor in children. Recent increases in survival rates are encouraging; however, survivors may experience a plethora of disease- and treatment-related complications that can persist into adulthood. Therapeutic exercise interventions have been shown to improve quality of survivorship in other pediatric cancer diagnoses. There is also evidence that goal-directed interventions are effective at improving motor activities, function, and self-care in children with complex health conditions. Yet, there is currently no evidence on the efficacy of goal-directed therapeutic exercise in pediatric PFBT survivors. The Physical ACTivity in Survivorship (PACTS) study aims to investigate the effects of a novel goal-directed therapeutic exercise program on cardiorespiratory fitness and physical activity-related goal attainment in pediatric survivors of PFBT.

Method

PFBT survivors, aged five to 17 years, who underwent surgery at least 12 months earlier and completed radiation therapy and/or chemotherapy at least 6 months prior will be recruited from the Queensland Children’s Hospital (Brisbane, Australia) (target n = 48). Following baseline assessment, participants are randomized into either the intervention or usual care group. The intervention group will receive weekly individualized, goal-directed exercise therapy delivered face-to-face for 12 weeks, along with an accompanying home-based program (three sessions per week). Outcomes will be assessed at baseline, immediately post-intervention, and at 6- and 12-months post-intervention. The primary outcomes are cardiorespiratory fitness (Peak VO2) and physical activity-related goal attainment. Secondary outcomes are cardiorespiratory endurance, high-level mobility skills, functional muscle strength, habitual physical activity, gait, balance, quality of life, fatigue, participation, perceived movement skill competence and parameters of body composition.

Discussion

PACTS is the first study to investigate the efficacy of goal-directed therapeutic exercise in children with PFBT and provide evidence needed to inform clinical practice recommendations for managing quality of survivorship in PFBT survivors.

Trial registration

ACTRN12619000841178.
Histological chorioamnionitis is associated with an increased risk of wheezing in preterm children less than 34 gestational weeks
Authors: Wang Xiaoli , Li Haiyuan , Zhang Qianqian , Shen Qianwen , Zhu Dan , Li Hong , Tang Zheng , Zhao Jiuru , Liu Zhiwei
Published: March 2021

Background

Chorioamnionitis is associated with various neonatal short- and long-term morbidities. The effect of chorioamnionitis on premature children’s outcomes remains controversial. The aim of this study is to investigate the relationship between histological chorioamnionitis (HCA) and physiological development, wheezing, and atopic diseases in preterm children.

Methods

Singleton, preterm children (< 34 weeks), whose mother underwent pathological placental examinations, were retrospectively enrolled and the outcomes were assessed at 24–40 months during follow-up. Wheezing and atopic diseases including eczema, food allergies, and allergic rhinitis were screened by a questionnaire along with medical diagnosis. Anthropometric indexes and blood pressure were measured. Cognitive and behavioural developments were assessed by the Gesell Development and Diagnosis Scale. Blood IgE and routine examination were analyzed with venous blood and serum metabolomic profiling was assessed via liquid chromatography-mass spectrometry (LC-MS). A multivariate logistic regression model was used to estimate the association between HCA and the current outcomes.

Results

Among the 115 enrolled children, 47 were exposed to HCA. The incidence of wheezing was significantly higher in children exposed to HCA, as 38.30% of children who were exposed to HCA and 16.18% of children who were not had been diagnosed with wheezing. After adjusting for related confounders in the multivariate logistic regression model, there remained a 2.72-fold increased risk of wheezing in children with HCA (adjusted odds ratio, aOR, 2.72; 95% confidence interval, 1.02–7.23). Moreover, 163 differential metabolites, such as butanoic acid, annotemoyin 1 and charine, were identified in the HCA exposed children’s serum. Enrichment analysis revealed that these compounds participated in diverse key metabolomic pathways relating to physical and neuro- developments, including glycerophospholipid, alpha-linolenic acid and choline metabolisms. There were no significant differences in atopic diseases, serum IgE, eosinophils’ level, anthropometric indexes, blood pressure, or cognitive or behavioural developments between the two groups.

Conclusion

HCA exposure is associated with an increased risk of wheezing in preterm children less than 34 gestational weeks.
Alcohol policies, firearm policies, and suicide in the United States: a lagged cross-sectional study
Authors: Coleman Sharon M. , Lira Marlene C. , Blanchette Jason , Heeren Timothy C. , Naimi Timothy S.
Published: March 2021

Background

Alcohol and firearms are commonly involved in suicide in the United States. State alcohol and firearm policies may impact alcohol and firearm related suicide, yet little is known about these relationships. This study examines relationships between state alcohol and firearm policies and suicides involving alcohol, guns, or both, and explores interactive policy associations.

Methods

Alcohol policies were assessed with the Alcohol Policy Scale. Firearm policies were assessed using the Gun Law Scorecard from Giffords Law Center. Suicide data from the National Violent Death Reporting System in 2015 covered 22 states. State- and individual-level GEE Poisson and logistic regression models assessed relationships between policies and firearm- and/or alcohol-involved suicides with a 1-year lag.

Results

In 2015, there were 8996 suicide deaths with blood alcohol concentration test results in the 22 included states. Of those deaths, alcohol and/or firearms were involved in 5749 or 63.9%. Higher alcohol and gun law scores were associated with reduced incidence rates and odds of suicides involving either alcohol or firearms (adjusted incidence rate ratios [IRR] 0.72 (95% CI 0.63, 0.83) for alcohol policies, 0.86 (95% CI 0.82, 0.90) for firearm policies). Relationships were similar for suicides involving both alcohol and firearms, and there was an interactive effect, such that states with restrictive policies for both had the lowest rates of suicides involving alcohol or guns.

Conclusions

More restrictive alcohol and firearm policies are associated with lower rates and odds of suicides involving alcohol or firearms, and alcohol and firearms, and may be a promising means by which to reduce suicide.
Formative research for the development of baby water, sanitation, and hygiene interventions for young children in the Democratic Republic of the Congo (REDUCE program)
Authors: Kuhl Jennifer , Bisimwa Lucien , Thomas Elizabeth D. , Williams Camille , Ntakirutimana Joseph , Coglianese Nicole , Bauler Sarah , François Ruthly , Sanvura Presence , Bisimwa Jean Claude , Mirindi Patrick , George Christine Marie
Published: March 2021

Background

Research exploring the unique exposure pathways to fecal pathogens for young children and innovative water, sanitation, and hygiene (WASH) interventions for susceptible pediatric populations is needed to reduce the burden of diarrheal diseases and stunting globally. The Reducing Enteropathy, Diarrhea, Undernutrition, and Contamination in the Environment (REDUCE) program seeks to 1) identify exposure pathways to fecal pathogens that are significant contributors to morbidity for young children in South Kivu, Democratic Republic of the Congo, and 2) develop and evaluate scalable interventions that reduce fecal contamination and exposure from these pathways. The formative research portion of the project sought to identify feasible and acceptable WASH interventions to modify behaviors found to be associated with diarrheal disease and impaired growth in our REDUCE cohort study.

Methods

Ninety-one semi-structured interviews, 6 focus group discussions, and a pilot study of 102 households were conducted during 24 months of formative research. Thirty-one interviews and six focus group discussions were conducted with caregivers, community health workers, and village leaders to explore existing WASH practices and to identify barriers and facilitators to WASH behaviors. Findings were organized using the Integrated Behavioral Model for Water, Sanitation and Hygiene to facilitate interpretation and identify determinants to Baby WASH behaviors in this setting. Care Group modules and enabling technology were developed based on exploratory findings and then revised during a two-part, iterative pilot study. Sixty interviews were conducted with participants in a pilot study of the REDUCE Baby WASH Care Group modules to learn about their experiences with the intervention.

Results

Six REDUCE Baby WASH Care Group modules were developed based on formative research findings and covered the following topics: 1) living with animals; 2) child mouthing of fomites and feces; 3) composting animal feces; 4) child feces disposal; 5) handwashing with soap; and 6) water treatment.

Conclusion

This study took a theory-driven and evidence-based approach to formative research and the development of the REDUCE Baby WASH Care Group modules. Intervention design focused on interrupting the exposure routes for infants and young children to fecal pathogens in the environment and promoting low-cost, low-burden Baby WASH behavioral recommendations and enabling technology. These developed REDUCE Baby WASH Care Group modules are currently being rolled out to over 1,000,000 beneficiaries in Democratic Republic of the Congo.
Poor self-rated oral health associated with poorer general health among Indigenous Australians
Authors: Ju Xiangqun , Hedges Joanne , Garvey Gail , Smith Megan , Canfell Karen , Jamieson Lisa
Published: March 2021

Background

Oral diseases negatively impact general health, affecting physical, psychological, social and emotional wellbeing, and ability to give back to community. The relationship between poor oral health, and general health and wellbeing among Indigenous Australians has not been documented. Working in partnership with seven Indigenous communities in South Australia, this study aimed to: 1) quantify self-rated oral health and health-related quality of life and; 2) investigate associations between poor self-rated oral health and general health among Indigenous Australian adults.

Methods

Data was collected from a large convenience sample of Indigenous Australians aged 18+ years from Feb 2018 to Jan 2019. General health-related quality of life, as the main outcome variable, was measured by calculating disutility scores with the five individual EQ-5D dimensions (EuroQol instrument: EQ-5D-5L), then classified as ‘no problem’ and ‘at least one problem’. Self-reported oral health, as the main explanatory, was dichotomised into ‘fair or poor’ and ‘excellent, very good or good’. Multivariable log-Poisson regression models were used to estimate associations between poor self-rated oral health and general health by calculating mean rate ratios (MRR) for disutility scores and prevalence ratios (PR) for individual dimensions, after adjusting for social-demographic characteristics and health-related behaviours.

Results

Data were available for 1011 Indigenous South Australian adults. The prevalence of ‘fair or poor’ self-rated oral health was 33.5%. The mean utility score was 0.82 (95% CI: 0.81–0.83). Compared with those rating their oral health as ‘excellent or very good or good’, those who rated their oral health as ‘fair or poor’ had a mean disutility score that was 1.6 (95% CI: 1.1–2.2) times higher, and the prevalence of at least one problem ranged from 90 to 160% higher for individual EQ-5D dimensions.

Conclusions

Fair or poor self-rated oral health among Indigenous persons in South Australia was associated with poor general health as measured by EQ-5D-5L disutility. The relationship was especially evident with respect to mobility, self-care and anxiety/depression. The findings emphasise the importance of oral health as predictors of general health among Indigenous Australians.
Outcomes of intra-articular calcaneal fractures: surgical treatment of 114 consecutive cases at a maximum care trauma center
Authors: Schindler Christin , Schirm Andreas , Zdravkovic Vilijam , Potocnik Primoz , Jost Bernhard , Toepfer Andreas
Published: March 2021

Background

The aim of this retrospective monocentric study was to investigate the outcomes of surgically treated intra-articular calcaneus fractures in a maximum care trauma center.

Methods

One hundred forty patients who had undergone surgery for intra-articular calcaneal fractures between 2002 and 2013 were included. One hundred fourteen cases with 129 fractures were eligible to participate in the study of which 80 were available for a clinical and radiological follow-up. 34 patients were followed up by telephone interview only. Outcome measures included the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score, Short Form 36 Health Status Survey (SF-36), complications, and subsequent surgeries.

Results

Mean follow-up was 91 months (range 12–183). The overall complication rate was 29% (37/129 ft). Disturbed wound healing (11%) and infection (5%) occurred most commonly. Non-union (4%) only occurred in smokers (p = 0.02). A high rate of posttraumatic subtalar arthritis (77%) and need for subsequent subtalar fusion (18%) without independent risk factors for subsequent subtalar fusion was found. The revision rate was high (60%) after primary fusion. Mean AOFAS-hindfoot score was 74 (Sanders I: 99, Sanders II: 74, Sanders III: 77, Sanders IV: 70). The postoperative Boehler angle improved significantly in all subgroups (p < 0.01). Patients with a decreased Boehler angle between postoperative images and the follow-up had significantly lower AOFAS hindfoot scores (p < 0.01).

Conclusions

Our data can aid decision-making in the treatment of calcaneal fractures. We advocate to use primary subtalar fusion with caution due to the high revision rate. Smoking status should always be considered.

Level of evidence: Level III, retrospective cohort study.
Compressive mechanical stress enhances susceptibility to interleukin-1 by increasing interleukin-1 receptor expression in 3D-cultured ATDC5 cells
Authors: Takeda Yuki , Niki Yasuo , Fukuhara Yusuke , Fukuda Yoshitsugu , Udagawa Kazuhiko , Shimoda Masayuki , Kikuchi Toshiyuki , Kobayashi Shu , Harato Kengo , Miyamoto Takeshi , Matsumoto Morio , Nakamura Masaya
Published: March 2021

Background

Mechanical overload applied on the articular cartilage may play an important role in the pathogenesis of osteoarthritis. However, the mechanism of chondrocyte mechanotransduction is not fully understood. The purpose of this study was to assess the effects of compressive mechanical stress on interleukin-1 receptor (IL-1R) and matrix-degrading enzyme expression by three-dimensional (3D) cultured ATDC5 cells. In addition, the implications of transient receptor potential vanilloid 4 (TRPV4) channel regulation in promoting effects of compressive mechanical loading were elucidated.

Methods

ATDC5 cells were cultured in alginate beads with the growth medium containing insulin-transferrin-selenium and BMP-2 for 6 days. The cultured cell pellet was seeded in collagen scaffolds to produce 3D-cultured constructs. Cyclic compressive loading was applied on the 3D-cultured constructs at 0.5 Hz for 3 h. The mRNA expressions of a disintegrin and metalloproteinases with thrombospondin motifs 4 (ADAMTS4) and IL-1R were determined with or without compressive loading, and effects of TRPV4 agonist/antagonist on mRNA expressions were examined. Immunoreactivities of reactive oxygen species (ROS), TRPV4 and IL-1R were assessed in 3D-cultured ATDC5 cells.

Results

In 3D-cultured ATDC5 cells, ROS was induced by cyclic compressive loading stress. The mRNA expression levels of ADAMTS4 and IL-1R were increased by cyclic compressive loading, which was mostly prevented by pyrollidine dithiocarbamate. Small amounts of IL-1β upregulated ADAMTS4 and IL-1R mRNA expressions only when combined with compressive loading. TRPV4 agonist suppressed ADAMTS4 and IL-1R mRNA levels induced by the compressive loading, whereas TRPV4 antagonist enhanced these levels. Immunoreactivities to TRPV4 and IL-1R significantly increased in constructs with cyclic compressive loading.

Conclusion

Cyclic compressive loading induced mRNA expressions of ADAMTS4 and IL-1R through reactive oxygen species. TRPV4 regulated these mRNA expressions, but excessive compressive loading may impair TRPV4 regulation. These findings suggested that TRPV4 regulates the expression level of IL-1R and subsequent IL-1 signaling induced by cyclic compressive loading and participates in cartilage homeostasis.
Validation of self-administered tests for screening for chronic pregnancy-related pelvic girdle pain
Authors: Fagevik Olsén Monika , Körnung Paulina , Kallin Sophie , Elden Helen , Kjellby Wendt Gunilla , Gutke Annelie
Published: March 2021

Background

Many women develop pelvic girdle pain (PGP) during pregnancy and about 10% have chronic pain several years after delivery. Self-administered pain provocation tests are one way to diagnose and evaluate this pain. Their validity in post-partum women is not yet studied.

The purpose of this study was to evaluate the validity of self-administered test for assessment of chronic pregnancy-related PGP several years after delivery.

Methods

Women who previously have had PGP during pregnancy and who participated in one of three RCT studies were invited to a postal follow up of symptoms including performance of self-administered tests after two, 6 or 11 years later, respectively. In total, 289 women returned the questionnaire and the test-results. Of these, a sub-group of 44 women with current PGP underwent an in-person clinical examination. Comparisons were made between test results in women with versus without PGP but also, in the sub-group, between the self-administered tests and those performed during the clinical examination.

Results

Fifty-one women reported PGP affecting daily life during the last 4 weeks, and 181 reported pain when performing at least one of the tests at home. Those with chronic PGP reported more positive tests (p < 0.001). There was no significant difference between diagnosis from the self-administered tests compared to tests performed during the in-person clinical examination (p = 0.305), either for anterior or posterior PGP. There were no significant differences of the results between the tests performed self-administered vs. during the clinical examination.

Conclusion

A battery of self-administered tests combined with for example additional specific questions or a pain-drawing can be used as a screening tool to diagnose chronic PGP years after delivery. However, the modified SLR test has limitations which makes its use questionable.
Open-label phase 3 study of diclofenac conjugated to hyaluronate (diclofenac etalhyaluronate: ONO-5704/SI-613) for treatment of osteoarthritis: 1-year follow-up
Authors: Nishida Yoshihiro , Kano Kazuyuki , Osato Taiki , Seo Takayuki
Published: March 2021

Background

We evaluated the 1-year safety and efficacy of diclofenac etalhyaluronate (DF-HA), a diclofenac-conjugated hyaluronate, in patients with osteoarthritis (OA).

Methods

In this multi-centre, open-label, noncomparative phase 3 study in Japan, patients with a diagnosis of knee, shoulder, elbow, hip, or ankle OA received an intra-articular (IA) injection of DF-HA 30 mg every 4 weeks for 1 year (13 times in total). The safety outcomes included treatment-emergent adverse events (TEAEs) and target joint structural changes by X-ray imaging tests. Efficacy outcomes included joint pain scores on an 11-point numerical rating scale. Concomitant use of analgesics was not restricted.

Results

Overall, 166 eligible patients were enrolled, comprising knee OA (n = 126) and other OA (n = 40). All TEAEs were experienced by 126/166 patients (75.9%). The incidence of treatment-related TEAEs was not associated with the treatment period. No significant worsening of joint status was observed in X-ray imaging tests at week 52 or at last assessment. The mean joint pain scores (± standard deviation) were 5.9 ± 1.2, 4.9 ± 1.9, and 3.1 ± 2.3 at baseline, and weeks 2 and 52, respectively. Improvement of pain score was observed after the first injection and was maintained until week 52 regardless of knee OA or other joint OA.

Conclusions

Repeated IA injections of DF-HA every 4 weeks for 1 year were well tolerated with no clinically significant adverse events indicating they might lead to the long-term improvement of OA symptoms. DF-HA might be a useful treatment for patients with OA.

Trial registration number

JapicCTI-183855 (First registered date: 6th February 2018).
Preoperatively elevated RDW-SD and RDW-CV predict favorable survival in intrahepatic cholangiocarcinoma patients after curative resection
Authors: Li Xingchen , Chen Qichen , Bi Xinyu , Zhao Jianjun , Li Zhiyu , Zhou Jianguo , Huang Zhen , Zhang Yefan , Mao Rui , Zhao Hong , Cai Jianqiang
Published: March 2021

Background

Recent studies suggest red blood cell distribution width (RDW) was a prognostic factor in various types of cancer patients, although the results are controversial. The objective of this study was to investigate the significance of RDW in patients with intrahepatic cholangiocarcinoma (ICC) after radical resection.

Method

The relationship between the preoperative serum RDW value and clinic pathological characteristics was analyzed in 157 ICC patients between January 2012 and June 2018 who underwent curative resection. X-tile software was used to determine 40.2 fl, 12.6% as the optimal cut-off value for RDW-SD and RDW-CV respectively. 153 patients were classified into the low RDW-SD (≤ 40.2, n = 53) group and the high RDW-SD (> 40.2, n = 104) group, low RDW-CV (≤ 12.6, n = 94) group and the high RDW-CV (> 12.6, n = 63). Based on the RDW-SD combined with RDW-CV (SCC), classified into SCC = 0, 1 and 2 group. Kaplan–Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival.

Results

Kaplan–Meier curve analysis showed that Patients with RDW-SD > 40.2 were significantly associated with better OS (P = 0.004, median OS: 68.0 months versus 17.0 months). Patients with RDW-CV > 12.6 were significantly associated with better OS (p = 0.030, median OS: not reach versus 22.0 months). Compared with a SCC = 0 or SCC = 1, SCC = 2 was significantly associated with better OS (p < 0.001, median OS: not reach versus 33.0 months versus 16, respectively). In the multivariate analysis, RDW-SD > 40.2 fl (HR = 0.446, 95% CI: 0.262–0.760, p = 0.003), RDW-CV > 12.6% (HR = 0.425, 95%CI: 0.230–0.783, p = 0.006), SCC = 2 (HR = 0.270, 95%CI: 0.133–0.549, p < 0.001) were associated with favorable OS. The multivariate analysis showed RDW-SD, RDW-CV and SCC level were not independent prognostic factors for DFS.

Conclusions

Preoperative low levels of RDW are associated with poor survival in ICC after curative resection. This provides a new way for predicting the prognosis of ICC patients and more targeted intervention measures.
The impact of a training programme incorporating the conceptual framework of the International Classification of Functioning (ICF) on knowledge and attitudes regarding interprofessional practice in Rwandan health professionals: a cluster randomized control trial
Authors: Sagahutu Jean Baptiste , Kagwiza Jeanne , Cilliers Francois , Jelsma Jennifer
Published: March 2021

Background

The first step in improving interprofessional teamwork entails training health professionals (HP) to acknowledge the role and value the contribution of each member of the team. The International Classification of Functioning, Disability and Health (ICF) has been developed by WHO to provide a common language to facilitate communication between HPs.

Objective

To determine whether ICF training programme would result in improved knowledge and attitudes regarding interprofessional practice within Rwandan district hospitals.

Design, setting and participants

A cluster randomised, single blinded, control trial design was used to select four district hospitals. Participants included physicians, social workers, physiotherapists, nutritionists, clinical psychologists/mental health nurses.

Intervention

Health professionals either received one day’s training in interprofessional practice (IPP) based on the ICF (experimental group) as a collaborative framework or a short talk on the topic (control group).

Outcome measures

Validated questionnaires were used to explore changes in knowledge and attitudes. Ethical approval was obtained from the relevant authorities.

Results

There were 103 participants in the experimental and 100 in the control group. There was no significant difference between Knowledge and Attitude scales at baseline. Post-intervention the experimental group (mean = 41.3, SD = 9.5) scored significantly higher on the knowledge scale than the control group (mean = 17.7, SD = 4.7 (t = 22.5; p < .001)). The median scores on the Attitude Scale improved in the Experimental group from 77.8 to 91.1%, whereas the median scores of the control remained approximately 80% (Adjusted Z = 10.72p < .001).

Conclusion

The ICF proved to be a useful framework for structuring the training of all HPs in IPP and the training resulted in a significant improvement in knowledge and attitudes regarding IPP. As suggested by the HPs, more training and refresher courses were needed for sustainability and the training should be extended to other hospitals in Rwanda. It is thus recommended that the framework can be used in interprofessional education and practice in Rwanda and possibly in other similar countries.

Trial registration

Name of the registry: Pan African Clinical Trial Registry.

Trial registration number:PACTR201604001185358.

Date of registration: 22/04/2016.

URL of trial registry record:www.pactr.org
Determining mutational burden and signature using RNA-seq from tumor-only samples
Authors: Jessen Erik , Liu Yuanhang , Davila Jaime , Kocher Jean-Pierre , Wang Chen
Published: March 2021

Background

Traditionally, mutational burden and mutational signatures have been assessed by tumor-normal pair DNA sequencing. The requirement of having both normal and tumor samples is not always feasible from a clinical perspective, and led us to investigate the efficacy of using RNA sequencing of only the tumor sample to determine the mutational burden and signatures, and subsequently molecular cause of the cancer. The potential advantages include reducing the cost of testing, and simultaneously providing information on the gene expression profile and gene fusions present in the tumor.

Results

In this study, we devised supervised and unsupervised learning methods to determine mutational signatures from tumor RNA-seq data. As applications, we applied the methods to a training set of 587 TCGA uterine cancer RNA-seq samples, and examined in an independent testing set of 521 TCGA colorectal cancer RNA-seq samples. Both diseases are known associated with microsatellite instable high (MSI-H) and driver defects in DNA polymerase ɛ (POLɛ). From RNA-seq called variants, we found majority (> 95%) are likely germline variants, leading to C > T enriched germline variants (dbSNP) widely applicable in tumor and normal RNA-seq samples. We found significant associations between RNA-derived mutational burdens and MSI/POLɛ status, and insignificant relationship between RNA-seq total coverage and derived mutational burdens. Additionally we found that over 80% of variants could be explained by using the COSMIC mutational signature-5, -6 and -10, which are implicated in natural aging, MSI-H, and POLɛ, respectively. For classifying tumor type, within UCEC we achieved a recall of 0.56 and 0.78, and specificity of 0.66 and 0.99 for MSI and POLɛ respectively. By applying learnt RNA signatures from UCEC to COAD, we were able to improve our classification of both MSI and POLɛ.

Conclusions

Taken together, our work provides a novel method to detect RNA-seq derived mutational signatures with effective procedures to remove likely germline variants. It can leads to accurate classification of underlying driving mechanisms of DNA damage deficiency.