bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between sedentary behaviour and indicators of stress: a systematic review
Authors: Teychenne Megan , Stephens Lena D. , Costigan Sarah A. , Olstad Dana Lee , Stubbs Brendon , Turner Anne I.
Published: October 2019

Background

Emerging evidence shows sedentary behaviour may be associated with mental health outcomes. Yet, the strength of the evidence linking sedentary behaviour and stress is still unclear. This study aimed to synthesise evidence regarding associations between time spent in sedentary behaviour and stress in adults.

Methods

A systematic search was conducted (January 1990 – September 2019). Following PRISMA guidelines, an evaluation of methodological quality, and best-evidence synthesis of associations between time in sedentary behaviour (including sitting time, TV viewing, computer use) and stress were presented. Twenty-six studies reporting on data from n = 72,795 people (age 18-98y, 62.7% women) were included.

Results

Across the studies (n = 2 strong-, n = 10 moderate- and n = 14 weak-quality), there was insufficient evidence that overall time spent in sedentary behaviour and sitting time were associated with stress, particularly when using self-report measures of sedentary behaviour or stress. There was strong evidence of no association between TV viewing, or computer use and stress. Amongst studies using objective measures of sedentary behaviour and/or stress there was also strong evidence of no association.

Conclusion

Although previous research suggested sedentary behaviour may be linked to mental health outcomes such as depression and anxiety, the evidence for an association between various types of sedentary behaviour and stress is limited in quality, and associations are either inconsistent or null. High-quality longitudinal/interventional research is required to confirm findings and determine the direction of associations between different contexts (i.e. purpose) and domains (i.e. leisure, occupational, transport) of sedentary behaviour and stress.
Do various personal hygiene habits protect us against influenza-like illness?
Authors: Bin Abdulrahman Amro K. , Bin Abdulrahman Khalid A. , Almadi Mansour K. , Alharbi Abdulrahman M. , Mahmoud Mahmoud A. , Almasri Mohammed S. , Alanazi Tariq R. , Alarifi Rakan A. , Kilani Abdullah A. , Albluwi Omar S. , Al Fraih Muaath A. , Al Otabi Yaser T. , Alanazi Hani O. , Almufarih Waleed A. , Alokayli Abdullah M. , Alwhibi Omar A.
Published: October 2019

Background

Several studies have reported an association between improvements in hand hygiene and the reductions in rates of intestinal parasitic diseases. However, only a some have addressed its link to the frequency of influenza-like illness. The current study aimed to find the correlation between personal hygiene habits and the frequency of influenza-like illness.

Methods

A cross-sectional study targeting 3000 participants conducted in Riyadh city, Saudi Arabia. A systematic random sampling methodology was applied for participant from different part of Riyadh city using a computer generating system. The researcher first started by calling each participant. A full explanation was given to each participant in details (from the purpose of the research, consent to answer the questionnaire, to the explanation of the outcome definition). Each point of the questionnaire was explained to them to make sure they had excellent comprehension, and therefore, respond accurately. Descriptive statistics and Odds Ratio and its 95% confidence intervals were used to determine the association between frequency of influenza-like illness and the studied variables.

Results

Two thousand eighty-two (69.4%) completed the questionnaire. The participants who spent 5–10 s in handwashing with soap and rubbing were at increased risk of more frequent influenza-like illness (odds ratio = 1.37, 1.08–1.75). Handwashing with soap and rubbing after handshaking is an independent protective habit against frequent influenza-like illness (adjusted OR = 0.59, 0.37–0.94).

Conclusion

The decrease of the frequency of influenza-like illness could be done through the following: getting the influenza vaccine annually, washing hands with soap and hand rubbing not less than 15 s after getting out of the bathroom, before and after handshaking and before eating. Soap companies should invent soaps that take less rubbing time to kill bacteria, and subsequently may maximize compliance in the community.
Examining the relationships between parent experiences and youth self-reports of slapping/spanking: a population-based cross-sectional study
Authors: Afifi Tracie O. , Fortier Janique , MacMillan Harriet L. , Gonzalez Andrea , Kimber Melissa , Georgiades Katholiki , Duncan Laura , Taillieu Tamara , Davila Isabel Garces , Struck Shannon
Published: October 2019

Background

Slapping/spanking is related to a number of poor health outcomes. Understanding what factors are related to the increased or decreased use of spanking/slapping is necessary to inform prevention. This study used a population-based sample to determine the prevalence of slapping/spanking reported by youth; the relationship between sociodemographic factors and slapping/spanking; and the extent to which parental exposures to victimization and maltreatment in childhood and current parental mental health, substance use and family circumstances, are associated with youth reports of slapping/spanking.

Methods

Data were from the 2014 Ontario Child Health Study, a provincially representative sample of households with children and youth aged 4–17 years. Self-reported lifetime slapping/spanking prevalence was determined using a sub-sample of youth aged 14–17 years (n = 1883). Parents/primary caregivers (i.e., person most knowledgeable (PMK) of the youth) self-reported their own childhood experiences including bullying victimization, slapping/spanking and child maltreatment, and current mental health, substance use and family circumstances including mental health functioning and emotional well-being, alcohol use, smoking, marital conflict and family functioning. Analyses were conducted in 2018.

Results

Living in urban compared to rural residence and family poverty were associated with decreased odds of slapping/spanking. PMK childhood experiences of physical and verbal bullying victimization, spanking, sexual abuse, emotional abuse, and exposure to physical intimate partner violence were associated with increased odds of youth reported slapping/spanking (adjusted odds ratio [AOR] ranged from 1.33–1.77). PMK experiences of physical abuse and exposure to emotional/verbal intimate partner violence in childhood was associated with decreased odds of youth reported slapping/spanking (AOR = 0.72 and 0.88, respectively). PMK’s higher levels of marital conflict, languishing to moderate mental health functioning and emotional well-being, and moderate or greater alcohol use were associated with increased odds of youth reported slapping/spanking (AOR ranged from 1.36–1.61).

Conclusions

It may be important to consider parent/primary caregiver’s childhood experiences with victimization and maltreatment along with their current parental mental health, substance use and family circumstances when developing and testing strategies to prevent slapping/spanking.
Functional variations of the TLR4 gene in association with chronic obstructive pulmonary disease and pulmonary tuberculosis
Authors: Li Zhongqi , Mao Xuhua , Liu Qiao , Song Huan , He Biyu , Shi Peiyi , Zhang Qun , Li Xiaona , Wang Jianming
Published: October 2019

Objective

Chronic obstructive pulmonary disease (COPD) and pulmonary tuberculosis (PTB) share a number of common risk factors, including innate immunity-related genetic factors. In the present study, we compared the role of genetic variations of theTLR4gene in susceptibility to COPD and PTB and illuminated the underlying molecular mechanism of functional single-nucleotide polymorphisms (SNPs).

Methods

A population-based case control study was performed in a Chinese Han population and included 152 COPD cases, 1601 PTB cases and 1727 controls. Five SNPs in theTLR4gene (rs10759932, rs2737190, rs7873784, rs11536889, and rs10983755) were genotyped using TaqMan allelic discrimination technology. We estimated the effects of SNPs using the odds ratio (OR) together with 95% confidence interval (CI). Dual-luciferase reporter vectors expressing different genotypes of SNPs were constructed and transfected into the human HEK 293 T cell line to explore their effects on potential transcription activity.

Results

After Bonferroni correction, the genetic polymorphisms of all five SNPs remained significantly associated with COPD, while rs10759932 and rs2737190 were also associated with PTB. Compared with rs10759932-TT, individuals carrying TC (OR: 0.42, 95% CI: 0.28–0.64) or CC (OR: 0.24, 95% CI: 0.09–0.63) had a significantly reduced risk of COPD. However, individuals carrying TC (OR: 1.28, 95% CI: 1.11–1.49) or CC (OR: 1.26, 95% CI: 0.98–1.62) had an increased risk of PTB. The OR (95% CI) for allele rs10759932-C was 0.45 (0.32–0.62) for COPD and 1.18 (1.07–1.32) for PTB. For rs2737190, heterozygous AG was related to a decreased risk of COPD (OR: 0.32, 95% CI: 0.21–0.49) and an increased risk of PTB (OR: 1.30, 95% CI: 1.11–1.52). The dual-luciferase reporter assay showed decreased transcription activity caused by rs10759932-C and rs2737190-G.

Conclusion

Genetic polymorphisms of rs10759932 and rs2737190 inTLR4are significantly related to both COPD and PTB but with inverse effects. The altered transcription activity caused by mutations in these two loci may partly explain the observed relationship.
Transfer of abductor hallucis tendon combined with scarf osteotomy versus single scarf osteotomy in moderate to severe hallux valgus deformity: a comparative retrospective cohort study
Authors: Xiong Yuan , Shen Bo , Hao Cheng , Xiao Kai , Wang Junwen , Fang Zhenhua
Published: October 2019

Background

Scarf osteotomy (SO) was broadly applied in moderate to severe hallux valgus (MSHV), and the results were satisfactory. However, due to the complicated pathologic changes in hallux valgus, the ideal surgical treatment is still controversial. Transfer of the abductor hallucis tendon combined with Scarf osteotomy (TAHTCSO) was an innovative alternative technique. This retrospective cohort study aimed to define if TAHTCSO mode resulted in improved outcomes as compared with the single SO in MSHV.

Methods

Of 73 patients (92 ft) with MSHV, 36 (45 ft) were treated through TAHTCSO and 37 ones (47 ft) through SO. The patients were assessed clinically and radiographically with a 24-month follow-up. They were assessed pre-operatively and post-operatively with intermetatarsal angle (IMA), hallux valgus angle (HVA), distal metatarsal articular angle (DMAA), first metatarsophalangeal joint range of motion (1#MTP ROM), as well as American Orthopaedic Foot and Ankle Society (AOFAS) forefoot scores and postoperative complications of surgery.

Results

Both cohorts had the same baseline feathures. All patients were followed up from 24 to 40 months, with a mean of 28.3 months. Patients in the TAHTCSO cohort had significantly decreased HVA at 6 months (p < 0.0001), 12 months (p < 0.0001), and 24 months (p < 0.0001) after surgery. 1#MTP had been increased slightly with non-statistic sense (p>0.05). IMA, DMAA and AOFAS also had not significantly difference at all followed time after surgery as compared with the SO cohort. The healing of osteotomies was observed within 8 weeks in the two cohorts. Two cases of hallus varus had been found in SO cohort and there were no cases of delayed healing and bone non-union in both cohorts.

Conclusion

In this retrospective cohort study, TAHTCSO had sufficient maintenance of the correction and improved functional performance thereby was a good alternative for MSHV, though it did not display a better result for MSHV compared to SO.
Standardized mounting method of (zebrafish) embryos using a 3D-printed stamp for high-content, semi-automated confocal imaging
Authors: Kleinhans David Simon , Lecaudey Virginie
Published: October 2019

Background

Developmental biology relies to a large extent on the observation and comparison of phenotypic traits through time using high resolution microscopes. In this context, transparent model organisms such as the zebrafish Danio rerio in which developing tissues and organs can be easily observed and imaged using fluorescent proteins have become very popular. One limiting factor however is the acquisition of a sufficient amount of data, in standardized and reproducible conditions, to allow robust quantitative analysis. One way to improve this is by developing mounting methods to increase the number of embryos that can be imaged simultaneously in near-to-identical orientation.

Results

Here we present an improved mounting method allowing semi-automated and high-content imaging of zebrafish embryos. It is based on a 3D-printed stamp which is used to create a 2D coordinate system of multiple μ-wells in an agarose cast. Each μ-well models a negative of the average zebrafish embryo morphology between 22 and 96 h-post-fertilization. Due to this standardized and reproducible arrangement, it is possible to define a custom well plate in the respective imaging software that allows for a semi-automated imaging process. Furthermore, the improvement in Z-orientation significantly reduces post-processing and improves comparability of volumetric data while reducing light exposure and thus photo-bleaching and photo-toxicity, and improving signal-to-noise ratio (SNR).

Conclusions

We present here a new method that allows to standardize and improve mounting and imaging of embryos. The 3D-printed stamp creates a 2D coordinate system of μ-wells in an agarose cast thus standardizing specimen mounting and allowing high-content imaging of up to 44 live or mounted zebrafish embryos simultaneously in a semi-automated, well-plate like manner on inverted confocal microscopes. In summary, image data quality and acquisition efficiency (amount of data per time) are significantly improved. The latter might also be crucial when using the services of a microscopy facility.
Impact of toothpaste on oral health-related quality of life in people with dentine hypersensitivity
Authors: Mason Stephen , Burnett Gary R. , Patel Nisha , Patil Avinash , Maclure Robert
Published: October 2019

Background

Dentine hypersensitivity can impact functional status and everyday activities such as eating and talking. This study aimed to assess changes in oral health-related quality of life measures in individuals with dentine hypersensitivity following long-term use (24 weeks) of a commercially available toothpaste marketed for dentine hypersensitivity relief.

Methods

This study was conducted across two sites and enrolled 75 adults with ≥2 non-adjacent sensitive teeth. Participants were assigned to twice-daily brushing with toothpaste containing 0.454% w/w stannous fluoride (1100 ppm fluoride). Every 4 weeks, participant-reported outcomes were assessed using the Dentine Hypersensitivity Experience Questionnaire (DHEQ), a condition specific oral health-related quality of life scale that has five domains and includes questions on social and emotional impact, restrictions, adaptations and effect on life overall. Responses to a clinically applied evaporative (air) stimulus were assessed using the examiner-observed Schiff sensitivity scale and Labelled Magnitude Scales (LMS), which included dentine hypersensitivity-specific descriptors of intensity, duration, tolerability and descriptive qualities of the participant’s response.

Results

Participant-reported outcomes demonstrated reduction of the impact of dentine hypersensitivity over time on health-related quality of life, as measured by the DHEQ. This reached statistical significance from Week 8 onwards (p < 0.0001 versus baseline) for the Total DHEQ score, with scores continually decreasing at each timepoint. Most domain scores followed a similar pattern. Statistically significant reductions were also detected for the examiner-observed Schiff Sensitivity Scale scores at all timepoints (including at 4 weeks) (p < 0.05), which were mirrored by LMS responses. The toothpaste was generally well-tolerated.

Conclusions

These results show that long-term use of a sensitivity toothpaste containing 0.454% w/w stannous fluoride has a beneficial, ongoing, impact on the oral health-related quality of life of people with dentine hypersensitivity.

Trial registration

This study was registered at Clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT02752958) on April 27, 2016.
Completion rate of physician orders for life-sustaining treatment for patients with metastatic or recurrent cancer: a preliminary, cross-sectional study
Authors: Kim Ju Won , Choi Jung Yoon , Jang Won Jin , Choi Yoon Ji , Choi Youn Seon , Shin Sang Won , Kim Yeul Hong , Park Kyong Hwa
Published: October 2019

Background

“End of life” is a difficult topic of conversation in East Asian cultures, even among patients and doctors who share a good rapport. In 2016, the Hospice, Palliative Care, and Life-Sustaining Treatment Decision-Making Act, which took the form of “Physician Orders for Life-Sustaining Treatment,” was introduced in South Korea. This study was conducted to investigate the completion rate of Physician Orders for Life-Sustaining Treatment in patients with advanced cancer on the active recommendation of physicians, as well as patients’ general attitudes toward end-of-life care.

Methods

We conducted a preliminary, cross-sectional descriptive survey on patients with advanced cancer. A total of 101 patients with advanced solid cancer agreed to participate in the study. The primary endpoint was the rate of completion of Physician Orders for Life-Sustaining Treatment based on a doctor’s suggestion. Written interviews were conducted to understand the perceptions and factors influencing patients’ decisions.

Results

Of the 101 patients, 72 (71.3%) agreed to prepare Physician Orders for Life-Sustaining Treatment. Patients who had an educational level of high school or higher were more likely to agree to complete Physician Orders for Life-Sustaining Treatment documentation as compared to the lower educational status group. More than half of the respondents who completed Physician Orders for Life-Sustaining Treatment documentation reported that they had more than a fair understanding of “life-sustaining care” or “Physician Orders for Life-Sustaining Treatment.” Participants’ reasons for Physician Orders for Life-Sustaining Treatment completion were diverse.

Conclusions

We found that highly educated patients, who understood the concept behind the policy well, tended to accept Physician Orders for Life-Sustaining Treatment without hesitation. Better education, information shared through the media, and conversations with health care providers might improve understanding of Physician Orders for Life-Sustaining Treatment in patients with cancer.
Glucose and lipid lowering effects of Enhydra fluctuans extract in cadmium treated normal and type-2 diabetic model rats
Authors: Hasan Mohammad Nazmul , Sabrin Farah , Rokeya Begum , Khan Md Shahinul Haque , Ahmed Mahtab Uddin , Matondo Abel , Billah Md Morsaline , Akter Salima
Published: October 2019

Background

Recent epidemiological and experimental studies suggest that cadmium and diabetes-related hyperglycemia may act synergistically to worsen metabolic regulation. The present study aims to evaluate the potential effects ofEnhydra fluctuansextract in diabetes and dyslipidemia in cadmium (CdCl2) induced- normal and type 2 diabetic model rats.

Method

Forty-eight Long-Evans rats were divided equally into the following six groups: Normal Control (N-C), Normal treated with CdCl2(N-Cd), Normal treated with plant extract (N-P), Normal treated with both plant extract and CdCl2(N-PCd), Diabetic treated with plant extract (DM-P) and Diabetic treated with both plant extract and CdCl2 (DM-PCd). Blood glucose and other biochemical parameters were estimated by the enzymatic colorimetric method. Histological analysis of liver and heart was done by the hematoxylin-eosin (H & E) method.

Results

Twenty-one days treatment ofE. fluctuansextracts at a dose of 200 mg/kg significantly reduced blood glucose level in N-PCd and DM-PCd (p < 0.05), and DM-P (p < 0.01) group. The plant extract had no direct effects on total blood lipids but, it had beneficial effects on TG/HDL-C ratio in N-P and DM-PCd groups (p < 0.05). Cd induction significantly reduced body weight [(N-Cd, N-PCd, DM-PCd) (p < 0.01)], and induced liver [N-Cd (p < 0.05), N-PCd,p < 0.001] and renal impairment [N-Cd (p < 0.05)]. In bi-variate association, a significant positive correlation between serum glucose and SGPT (p < 0.05) as well as SGPT and TG/HDL ratio (p = 0.019) was found in DM-P and in the merged group. The histology of liver and heart showed severe damages including inflammation, nuclear pyknosis, loss of myocardial fibers, necrosis and fibrosis in the Cd treated groups compared to plant treated groups.

Conclusion

E. fluctuansseems to have potent antihyperglycemic effects in diabetes and Cd toxicity along with partial antidyslipidemic properties in euglycemic and diabetic rats. Our study suggests a novel oral antihyperglycemic agent in the present environmental context.
Are there decision support tools that might strengthen the health system for perinatal care in South African district hospitals? A review of the literature
Authors: Nkwanyana Ntombifikile Maureen , Voce Anna Silvia
Published: October 2019

Background

South Africa has a high burden of perinatal deaths in spite of the availability of evidence-based interventions. The majority of preventable perinatal deaths occur in district hospitals and are mainly related to the functioning of the health system. Particularly, leadership in district hospitals needs to be strengthened in order to decrease the burden of perinatal mortality. Decision-making is a key function of leaders, however leaders in district hospitals are not supported to make evidence-based decisions. The aim of this research was to identify health system decision support tools that can be applied at district hospital level to strengthen decision-making in the health system for perinatal care in South Africa.

Methods

A structured approach, the systematic quantitative literature review method, was conducted to find published articles that reported on decision support tools to strengthen decision-making in a health system for perinatal, maternal, neonatal and child health. Articles published in English between 2003 and 2017 were sought through the following search engines: Google Scholar, EBSCOhost and Science Direct. Furthermore, the electronic databases searched were: Academic Search Complete, Health Source – Consumer Edition, Health Source – Nursing/Academic Edition and MEDLINE.

Results

The search yielded 6366 articles of which 43 met the inclusion criteria for review. Four decision support tools identified in the articles that met the inclusion criteria were the Lives Saved Tool, Maternal and Neonatal Directed Assessment of Technology model, OneHealth Tool, and Discrete Event Simulation. The analysis reflected that none of the identified decision support tools could be adopted at district hospital level to strengthen decision-making in the health system for perinatal care in South Africa.

Conclusion

There is a need to either adapt an existing decision support tool or to develop a tool that will support decision-making at district hospital level towards strengthening the health system for perinatal care in South Africa.
Life satisfaction in Norwegian medical doctors: a 15-year longitudinal study of work-related predictors
Authors: Mahmood Javed Iqbal , Grotmol Kjersti Støen , Tesli Martin , Moum Torbjørn , Andreassen Ole , Tyssen Reidar
Published: October 2019

Background

Despite many recent studies on burn-out and dissatisfaction among American medical doctors, less is known about doctors in the Scandinavian public health service. The aims of this study were to analyse long-term work-related predictors of life satisfaction among established doctors in Norway and to identify predictors in a subgroup of doctors who reported a decline in life satisfaction.

Methods

Two nationwide cohorts of doctors (n = 1052), who graduated medical school 6 years apart, were surveyed at graduation from medical school (T1, 1993/94 and 1999), and 4 (T2), 10 (T3), and 15 (T4) years later. Work-related predictors of life satisfaction (three items) obtained at T2 to T4 were analysed. Individual and lifestyle confounders were controlled for using mixed-models repeated-measures analyses, and logistic regression analyses were applied to identify predictors of the decrease in life satisfaction.

Results

Ninety per cent (947/1052) responded at least once, and 42% (450/1052) responded at all four times. Work-related predictors of higher life satisfaction in the adjusted model were work–home stress (β = − 0.20, 95% confidence interval [CI] = − 0.25 to − 0.16,p < 0.001), perceived job demands (β = − 0.10, CI = − 0.15 to − 0.05,p < 0.001), and colleague support (β = 0.05, CI = 0.04 to 0.07,p < 0.001). The new adjusted individual predictors that we identified included female gender, reality weakness trait, and problematic drinking behaviour. Neuroticism trait and low colleague support predicted a decrease in life satisfaction.

Conclusions

Work–home stress, perceived job demands, and colleague support were the most important predictors of life satisfaction related to doctors’ work. When personality traits were controlled for, female doctors were more satisfied with their life than male doctors. These findings suggest that improving work-related factors with targeted interventions, including a supportive work environment, may increase life satisfaction among doctors.
Development and validation of a novel MR imaging predictor of response to induction chemotherapy in locoregionally advanced nasopharyngeal cancer: a randomized controlled trial substudy (NCT01245959)
Authors: Dong Di , Zhang Fan , Zhong Lian-Zhen , Fang Meng-Jie , Huang Cheng-Long , Yao Ji-Jin , Sun Ying , Tian Jie , Ma Jun , Tang Ling-Long
Published: October 2019

Background

In locoregionally advanced nasopharyngeal carcinoma (LANPC) patients, variance of tumor response to induction chemotherapy (ICT) was observed. We developed and validated a novel imaging biomarker to predict which patients will benefit most from additional ICT compared with chemoradiotherapy (CCRT) alone.

Methods

All patients, including retrospective training (n = 254) and prospective randomized controlled validation cohorts (a substudy of NCT01245959,n = 248), received ICT+CCRT or CCRT alone. Primary endpoint was failure-free survival (FFS). From the multi-parameter magnetic resonance images of the primary tumor at baseline, 819 quantitative 2D imaging features were extracted. Selected key features (according to their interaction effect between the two treatments) were combined into an Induction Chemotherapy Outcome Score (ICTOS) with a multivariable Cox proportional hazards model using modified covariate method. Kaplan-Meier curves and significance test for treatment interaction were used to evaluate ICTOS, in both cohorts.

Results

Three imaging features were selected and combined into ICTOS to predict treatment outcome for additional ICT. In the matched training cohort, patients with a high ICTOS had higher 3-year and 5-year FFS in ICT+CCRT than CCRT subgroup (69.3% vs. 45.6% for 3-year FFS, and 64.0% vs. 36.5% for 5-year FFS; HR = 0.43, 95% CI = 0.25–0.74,p = 0.002), whereas patients with a low ICTOS had no significant difference in FFS between the subgroups (p = 0.063), with a significant treatment interaction (pinteraction <  0.001). This trend was also found in the validation cohort with high (n = 73, ICT+CCRT 89.7% and 89.7% vs. CCRT 61.8% and 52.8% at 3-year and 5-year; HR = 0.17, 95% CI = 0.06–0.51,p <  0.001) and low ICTOS (n = 175,p = 0.31), with a significant treatment interaction (pinteraction = 0.019). Compared with 12.5% and 16.6% absolute benefit in the validation cohort (3-year FFS from 69.9 to 82.4% and 5-year FFS from 63.4 to 80.0% from additional ICT), high ICTOS group in this cohort had 27.9% and 36.9% absolute benefit. Furthermore, no significant survival improvement was found from additional ICT in both groups after stratifying low ICTOS patients into low-risk and high-risks groups, by clinical risk factors.

Conclusion

An imaging biomarker, ICTOS, as proposed, identified patients who were more likely to gain additional survival benefit from ICT+CCRT (high ICTOS), which could influence clinical decisions, such as the indication for ICT treatment.

Trial registration

ClinicalTrials.gov,NCT01245959. Registered 23 November 2010.
Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions
Authors: Ramsauer Anna Sophie , Wachoski-Dark Garrett Louis , Fraefel Cornel , Tobler Kurt , Brandt Sabine , Knight Cameron Greig , Favrot Claude , Grest Paula
Published: October 2019

Background

There is growing evidence that equine papillomavirus type 2 (EcPV2) infection is causally associated with the development of equine genital squamous cell carcinomas (SCCs). Early stages of disease present clinically as plaques or wart-like lesions which can gradually progress to tumoural lesions. Histologically these lesions are inconsistently described as benign hyperplasia, papilloma, penile intraepithelial neoplasia (PIN), carcinoma in situ (CIS) or SCC. Guidelines for histological classification of early SCC precursor lesions are not precisely defined, leading to potential misdiagnosis. The aim of this study was to identify histologic criteria and diagnostic markers allowing for a more accurate diagnosis of EcPV2-associated equine penile lesions.

Results

A total of 61 archived equine penile lesions were histologically re-assessed and classified as benign hyperplasia, papilloma, CIS or SCC. From these, 19 representative lesions and adjacent normal skin were comparatively analysed for the presence of EcPV2 DNA and transcripts using PCR and RNA in situ hybridisation (RISH). All lesional samples were positive by EcPV2 PCR and RISH, while adjacent normal skin was negative. RISH analysis yielded signal distribution patterns that allowed distinction of early (hyperplasia, papilloma) from late stage lesions (CIS, SCC). Subsequently, the 19 lesions were further assessed for expression of p53, Ki67, MCM7 and MMP1 by immunohistochemistry (IHC). All four proteins were expressed in both normal and lesional tissue. However, p53 expression was up-regulated in basal keratinocyte layers of papillomas, CIS and SCCs, as well as in upper keratinocyte layers of CIS and SCCs. MCM7 expression was only up-regulated in upper proliferating keratinocyte layers of papillomas, CIS and SCCs.

Conclusion

This study proposes combining a refined histological protocol for analysis of equine penile lesions with PCR- and/or RISH based EcPV2-screening and p53/MCM7 IHC to more accurately determine the type of lesion. This may help to guide the choice of optimum treatment strategy, especially at early stages of disease.
Characterization of five newly derived canine osteosarcoma cell lines
Authors: Wilson-Robles Heather , Franks Kelli , Pool Roy , Miller Tasha
Published: October 2019

Background

Canine and human osteosarcomas (OS) are notably similar and have a high rate of metastasis. There is a poor understanding of the tumor development process, predisposing causes, and varying levels of aggression among different cell lines. By characterizing newly developed canine osteosarcoma cell lines, treatments for people and pets can be developed. Of the seven subtypes of OS, three are represented in this group: osteoblastic (the most common), fibroblastic, and giant cell variant. To our knowledge, there are no other giant cell variant canine OS cell lines in the published literature and only one canine fibroblastic osteosarcoma cell line. Understanding the differences between the histologic subtypes in dogs will help to guide comparative research.

Results

Alkaline phosphatase expression was ubiquitous in all cell lines tested and invasiveness was variable between the cell lines tested. Invasiveness and oxidative damage were not correlated with in vivo growth rates, where TOT grew the fastest and had the higher percentage of mice with metastatic lesions. TOL was determined to be the most chemo-resistant during cisplatin chemotherapy while TOM was the most chemo-sensitive.

Conclusions

Further comparisons and studies using these cell lines may identify a variety of characteristics valuable for understanding the disease process and developing treatments for osteosarcoma in both species.

Some of this data was presented as a poster by KMF at the August 5th, 2017 National Veterinary Scholars Program in Bethesda, MA.

Characterization of 5 newly generated canine osteosarcoma cell lines.

Kelli Franks, Tasha Miller, Heather Wilson-Robles.
Role of XIAP gene overexpressed bone marrow mesenchymal stem cells in the treatment of cerebral injury in rats with cerebral palsy
Authors: Deng Wenjing , Fan Chenghe , Fang Yanbo , Zhao Yanan , Wei Yamin , Li Meng , Teng Junfang
Published: October 2019

Background

This study is performed to investigate the effects of adenovirus-mediated X-linked inhibitor of apoptosis protein (XIAP) overexpressed bone marrow mesenchymal stem cells (BMSCs) on brain injury in rats with cerebral palsy (CP).

Methods

Rat’s BMSCs were cultured and identified. The XIAP gene of BMSCs was modified by adenovirus expression vector Ad-XIAP-GFP. The rat model of CP with ischemia and anoxia was established by ligating the left common carotid artery and anoxia for 2 h, and BMSCs were intracerebroventricularly injected to the modeled rats. The mRNA and protein expression of XIAP in brain tissue of rats in each group was detected by RT-qPCR and western blot analysis. The neurobehavioral situation, content of acetylcholine (Ach), activity of acetylcholinesterase (AchE), brain pathological injury, apoptosis of brain nerve cells and the activation of astrocytes in CP rats were determined via a series of assays.

Results

Rats with CP exhibited obvious abnormalities, increased Ach content, decreased AchE activity, obvious pathological damage, increased brain nerve cell apoptosis, as well as elevated activation of astrocyte. XIAP overexpressed BMSCs improved the neurobehavioral situation, decreased Ach content and increased AchE activity, attenuated brain pathological injury, inhibited apoptosis of brain nerve cells and the activation of astrocytes in CP rats.

Conclusion

Our study demonstrates that XIAP overexpressed BMSCs can inhibit the apoptosis of brain nerve cells and the activation of astrocytes, increase AchE activity, and inhibit Ach content, so as to lower the CP caused by cerebral ischemia and hypoxia in rats.
The role of exosomal PD-L1 in tumor progression and immunotherapy
Authors: Xie Feiting , Xu Mengxue , Lu Jian , Mao Lingxiang , Wang Shengjun
Published: October 2019

Programmed death ligand 1 (PD-L1), a type I transmembrane protein, binds to its receptor PD-1 to suppress the activation of T cells, thereby maintaining immunological homeostasis. In contrast, tumor cells highly express PD-L1, which binds to receptor PD-1 expressed on activated T cells, leading to immune escape. Anti-PD-1/PD-L1 immune checkpoint therapy blocks the binding of PD-1/PD-L1 to reinvigorate the exhausted T cells, thereby inhibiting tumor growth. Exosomes are biologically active lipid-bilayer nanovesicles secreted by various cell types that mediate intercellular signal communication. Numerous studies have shown that tumor cells are able to promote tumor epithelial-mesenchymal transition, angiogenesis, and immune escape by releasing exosomes. Recent studies imply that tumor-derived exosomes could carry PD-L1 in the same membrane topology as the cell surface, thereby resisting immune checkpoint therapy. In this review, we mainly discuss the role of exosomes in the regulation of tumor progression and the potential resistance mechanism to immunotherapy via exosomal PD-L1. In addition, we propose that exosomal PD-L1 may have the potential to be a target to overcome resistance to anti-PD-1/PD-L1 antibody therapy.
Differential placental ceramide levels during gestational diabetes mellitus (GDM)
Authors: Mejia Juan F. , Hirschi Kelsey M. , Tsai Kary Y. F. , Long Matthew G. , Tullis Benton C. , Bitter Eliza E. K. , Bikman Benjamin T. , Reynolds Paul R. , Arroyo Juan A.
Published: October 2019

Background

Gestational diabetes mellitus (GDM) is associated with important factors that influence fetal development. Sphingolipids are known to be associated with the development of diabetes. Our objective was to examine ceramide, a key sphingolipid, hyperosmolarity, and apoptosis in placentas from GDM patients treated with insulin or diet.

Methods

Ceramide levels were assessed in placental tissues using immunohistochemistry. Immunoblot was performed to quantify serine palmitoyltransferase (SPT), the rate-limiting enzyme in ceramide biosynthesis, NFAT5, SMIT, AR, caspase 3 and the X-linked inhibitor of apoptosis. Trophoblast cells were treated with insulin or ceramide and assessments for mitochondrial respiration, caspase 3 and XIAP were also performed.

Results

Immunohistochemistry showed increased ceramides in the placental villous trophoblasts of the insulin-treated GDM patients. Nuclear SPT was upregulated only in the insulin-treated GDM placenta when compared to controls. Nuclear NFAT5 was also increased in the GDM placenta. Active caspase 3 was elevated in placentas from both insulin- and diet-treated GDM patients. Mitochondrial respiration was decreased in trophoblasts treated with ceramide. Active caspase was not changed while XIAP protein was increased in trophoblasts treated with ceramide.

Conclusions

Our findings confirm the presence of ceramide in the human placenta of control and GDM patients. Furthermore, we conclude that ceramide is increased in the placental trophoblast during insulin treatment and that its upregulation correlates with elevated NFAT5, SMIT, increased apoptosis and decreased trophoblast mitochondrial respiration.
Tibial post fracture pain is reduced in kinin receptors deficient mice and blunted by kinin receptor antagonists
Authors: Minville Vincent , Mouledous Lionel , Jaafar Acil , Couture Réjean , Brouchet Anne , Frances Bernard , Tack Ivan , Girolami Jean-Pierre
Published: October 2019

Background

Tibial fracture is associated with inflammatory reaction leading to severe pain syndrome. Bradykinin receptor activation is involved in inflammatory reactions, but has never been investigated in fracture pain.

Methods

This study aims at defining the role of B1 and B2-kinin receptors (B1R and B2R) in a closed tibial fracture pain model by using knockout mice for B1R (B1KO) or B2R (B2KO) and wild-type (WT) mice treated with antagonists for B1R (SSR 240612 and R954) and B2R (HOE140) or vehicle. A cyclooxygenase (COX) inhibitor (ketoprofen) and an antagonist (SB366791) of Transient Receptor Potential Vaniloid1 (TRPV1) were also investigated since these pathways are associated with BK-induced pain in other models. The impact on mechanical and thermal hyperalgesia and locomotion was assessed by behavior tests. Gene expression of B1R and B2R and spinal cord expression of c-Fos were measured by RT-PCR and immunohistochemistry, respectively.

Results

B1KO and B2KO mice demonstrated a reduction in post-fracture pain sensitivity compared to WT mice that was associated with decreased c-Fos expression in the ipsilateral spinal dorsal horn in B2KO. B1R and B2R mRNA and protein levels were markedly enhanced at the fracture site. B1R and B2R antagonists and inhibition of COX and TRPV1 pathways reduced pain in WT. However, the analgesic effect of the COX-1/COX-2 inhibitor disappeared in B1KO and B2KO. In contrast, the analgesic effect of the TRPV1 antagonist persisted after gene deletion of either receptor.

Conclusions

It is suggested that B1R and B2R activation contributes significantly to tibial fracture pain through COX. Hence, B1R and B2R antagonists appear potential therapeutic agents to manage post fracture pain.
The impact on anatomical landmark identification after an ultrasound-guided palpation intervention: a pilot study
Authors: Cho John Chinsuk , Reckelhoff Kenneth
Published: October 2019

Background

To determine whether a discrepancy exists in identifying three musculoskeletal landmarks (medial meniscus, lateral malleolus and lateral epicondyle of the humerus) and whether ultrasound-guided (US-guided) palpation intervention can reduce that discrepancy and improve localization for chiropractic interns.

Methods

Sixteen chiropractic interns were asked to identify three subcutaneous anatomical landmarks before/ after the intervention and at a 3-day follow-up. The intervention was a three-minute US-guided demonstration of the landmarks after the intern’s initial localization. The primary outcome measure was the change in distance between the intern’s landmark identification. Non-normal data were analyzed with the Friedman’s and Wilcoxon signed rank tests. Discrepancy between examiner-determined landmarks and intern-identified landmarks at the initial time point was assessed with a 1-sample Wilcoxon signed rank test.

Results

All locations demonstrated an initial discrepancy between examiner-determined landmarks and intern-identified landmarks at the initial time point. Overall, a statistically significant difference was noted in the identification of the medial meniscus (p = 0.012) and lateral malleolus (p = 0.001), but not at the lateral epicondyle (p = 0.086). For the before and immediately after comparison, a significant improvement was found with the medial meniscus (p = 0.005) and lateral malleolus (p = 0.002). The 3-day post-intervention comparison found an improvement only for the lateral malleolus (p = 0.008).

Conclusion

This pilot study demonstrated palpatory discrepancy at identifying all three landmarks. Our data suggests that US-guided palpation intervention seems to improve an intern’s ability to palpate two landmarks (medial meniscus and lateral malleolus) post-intervention.
Measurable residual disease at myeloablative allogeneic transplantation in adults with acute lymphoblastic leukemia: a retrospective registry study on 2780 patients from the acute leukemia working party of the EBMT
Authors: Pavlů Jiří , Labopin Myriam , Niittyvuopio Riitta , Socié Gerard , Yakoub-Agha Ibrahim , Wu Depei , Remenyi Peter , Passweg Jakob , Beelen Dietrich W. , Aljurf Mahmoud , Kröger Nicolaus , Labussière-Wallet Hélène , Perić Zinaida , Giebel Sebastian , Nagler Arnon , Mohty Mohamad
Published: October 2019

Background

Assessment of measurable residual disease (MRD) is rapidly transforming the therapeutic and prognostic landscape of a wide range of hematological malignancies. Its prognostic value in acute lymphoblastic leukemia (ALL) has been established and MRD measured at the end of induction is increasingly used to guide further therapy. Although MRD detectable immediately before allogeneic hematopoietic cell transplantation (HCT) is known to be associated with poor outcomes, it is unclear if or to what extent this differs with different types of conditioning.

Methods

In this retrospective registry study, we explored whether measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia is associated with different outcomes in recipients of myeloablative total body irradiation (TBI)-based versus chemotherapy-based conditioning. We analyzed outcomes of 2780 patients (median age 38 years, range 18–72) who underwent first HCT in complete remission between 2000 and 2017 using sibling or unrelated donors.

Results

In 1816 of patients, no disease was detectable, and in 964 patients, MRD was positive. Conditioning was TBI-based in 2122 (76%) transplants. In the whole cohort MRD positivity was a significant independent factor for lower overall survival (OS) and leukemia-free survival (LFS), and for higher relapse incidence (RI), with respective hazard ratios (HR, 95% confidence intervals) of 1.19 (1.02–1.39), 1.26 (1.1–1.44), and 1.51 (1.26–1.8). TBI was associated with a higher OS, LFS, and lower RI with HR of 0.75 (0.62–0.90), 0.70 (0.60–0.82), and 0.60 (0.49–0.74), respectively. No significant interaction was found between MRD status and conditioning. When investigating the impact of MRD separately in the TBI and chemotherapy-based conditioning cohorts by multivariate analysis, we found MRD positivity to be associated with lower OS and LFS and higher RI in the TBI group, and with higher RI in the chemotherapy group. TBI-based conditioning was associated with improved outcomes in both MRD-negative and MRD-positive patients.

Conclusions

In this large study, we confirmed that patients who are MRD-negative prior to HCT achieve superior outcomes. This is particularly apparent if TBI conditioning is used. All patients with ALL irrespective of MRD status benefit from TBI-based conditioning in the myeloablative setting.
Advances in omics-based methods to identify novel targets for malaria and other parasitic protozoan infections
Authors: Cowell Annie N. , Winzeler Elizabeth A.
Published: October 2019

A major advance in antimalarial drug discovery has been the shift towards cell-based phenotypic screening, with notable progress in the screening of compounds against the asexual blood stage, liver stage, and gametocytes. A primary method for drug target deconvolution in Plasmodium falciparum is in vitro evolution of compound-resistant parasites followed by whole-genome scans. Several of the most promising antimalarial drug targets, such as translation elongation factor 2 (eEF2) and phenylalanine tRNA synthetase (PheRS), have been identified or confirmed using this method. One drawback of this method is that if a mutated gene is uncharacterized, a substantial effort may be required to determine whether it is a drug target, a drug resistance gene, or if the mutation is merely a background mutation. Thus, the availability of high-throughput, functional genomic datasets can greatly assist with target deconvolution. Studies mapping genome-wide essentiality in P. falciparum or performing transcriptional profiling of the host and parasite during liver-stage infection with P. berghei have identified potentially druggable pathways. Advances in mapping the epigenomic regulation of the malaria parasite genome have also enabled the identification of key processes involved in parasite development. In addition, the examination of the host genome during infection has identified novel gene candidates associated with susceptibility to severe malaria. Here, we review recent studies that have used omics-based methods to identify novel targets for interventions against protozoan parasites, focusing on malaria, and we highlight the advantages and limitations of the approaches used. These approaches have also been extended to other protozoan pathogens, including Toxoplasma, Trypanosoma, and Leishmania spp., and these studies highlight how drug discovery efforts against these pathogens benefit from the utilization of diverse omics-based methods to identify promising drug targets.