bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneous neurodevelopmental disorders in children with Kawasaki disease: what is new today?
Authors: Lin Chien-Heng , Lin Wei-De , Chou I-Ching , Lee Inn-Chi , Hong Syuan-Yu
Published: November 2019

Background

Kawasaki disease (KD) is a common vasculitis of childhood in East Asia. The complications of KD ascribed to long-term cardiovascular sequelae are considerably diverse. Although studies have investigated neurodevelopmental problems following KD in the past few decades, they have reported inconsistent conclusions. This study investigated potential epilepsy and associated neurodevelopmental disorders (NDDs) following KD in Taiwanese children.

Methods

We retrospectively analyzed the data of children aged < 18 years with clinically diagnosed KD from January 1, 2005, to December 31, 2015. These patients were followed up to estimate the prevalence of epilepsy and associated NDDs in comparison with the prevalence in general pediatric population in Taiwan and worldwide.

Results

A total of 612 patients with an average age of 1.6 years were included. The prevalence of associated NDDs was 16.8% (n = 103/612) in the study group, which consisted of epilepsy, intellectual disability (ID), autism spectrum disorders, Tourette syndrome (TS), attention deficit hyperactivity disorder, (ADHD), and others. Moreover, children with KD had a higher prevalence of epilepsy and TS in both Taiwan and worldwide (epilepsy: 2.61% in the KD group vs 0.33% in Taiwan and 0.05–0.8% in worldwide, p < 0.05; TS: 2.77% in the KD group vs 0.56% in Taiwan and 0.3–1% in worldwide, p < 0.05). The prevalence of ID, ADHD, and developmental language disorders was not significantly different between our study patients and those in Taiwan or worldwide.

Conclusions

Results revealed a higher prevalence rate of NDDs, especially epilepsy and TS, in Taiwanese children with KD than in the general pediatric population in Taiwan. However, these NDDs could be heterogeneous. Children diagnosed with KD were followed up because they had a higher risk of heterogeneous NDDs.
Feasibility of a guided participation discharge program for very preterm infants in a neonatal intensive care unit: a randomized controlled trial
Authors: Lee S. Y. , Chau J. P. C. , Choi K. C. , Lo S. H. S.
Published: November 2019

Background

Previous studies showed that parents of very preterm infants expressed feelings of incompetence and experienced high levels of stress upon the discharge of their infants. We conducted a systematic review of seven studies and observed potential benefits for parental outcomes when using discharge interventions that adopted guided participation (GP). More evidence is needed on the effective doses of discharge interventions underpinned by the principles of GP.

Aim

To investigate the feasibility and preliminarily estimate the effects on parental competence and stress outcomes of a newly developed, nurse-led, GP discharge program for mothers of very preterm infants.

Methods

A two-arm randomized controlled trial was conducted in a neonatal intensive care unit (NICU). Mothers of infants with gestational ages of ≤32 weeks who had no congenital malformations and did not need to undergo major surgeries were recruited. All mothers were the primary caregivers to their infants. The intervention group received a nurse-led GP discharge intervention (three structured 30- to 60-min GP sessions and one follow-up phone call). The control group received usual care. The parental outcomes were measured using the Parenting Sense of Competence Scale (C-PSOC) and Perceived Stress Scale (C-PSS) at baseline (T0), on the day of discharge (T1), after the follow-up phone call (within 72 h after discharge) (T2), and 1 month after discharge (T3). The outcomes were analyzed using generalized estimating equations based on intention-to-treat principles.

Results

Thirty infant–mother dyads were recruited. Greater improvements in the C-PSOC score were observed in the intervention group than in the control group at T1 and T2, although these differences were statistically insignificant. The intervention group exhibited greater improvements than the control group in the C-PSS scores at T1, T2, and T3, although these differences were also not statistically significant.

Conclusions

The findings suggest that a GP discharge intervention could improve parenting competence and stress among mothers with very preterm infants. The absence of adverse events suggests that the GP discharge intervention could be feasibly implemented in NICU settings. This feasibility study was not powered to determine the effectiveness of the intervention but is anticipated to lay the foundation for a future full-scale study.

Trial registration

ClinicalTrials.gov Identifier: NCT03668912. Date of registration: 13 September 2018 (retrospectively registered).
The development of a brief screener for autism using item response theory
Authors: Mårland Caroline , Lubke Gitta , Degl’Innocenti Alessio , Råstam Maria , Gillberg Christopher , Nilsson Thomas , Lundström Sebastian
Published: November 2019

Background

Brief screening instruments focusing on autism spectrum disorder (ASD) that can be administered in primary care are scarce; there is a need for shorter and more precise instruments. The Autism–Tics, AD/HD and other Comorbidities inventory (A-TAC) has previously been validated for ASD reporting excellent validity. This study aims to determine the psychometric properties of each item in the ASD domain (17 items) in the A–TAC using item response theory (IRT), and thereby construct and validate a short form that could be used as a screening instrument in the general population.

Methods

Since 2004, parents of all 9-year-old Swedish twins have been invited to participate in a telephone interview in the Child and Adolescent Twin Study in Sweden (CATSS). The CATSS is linked to the National Patient Register (NPR), which includes data from in- and outpatient care. Data on ASD (A-TAC) collected in CATSS were compared with diagnoses from the NPR. Diagnoses that had been made both before (previous validity) and after (predictive validity) the interviews were included. The sample was divided into a developmental sample and a validation sample. An IRT model was fitted to the developmental sample and item parameters were used to select a subset of items for the short form. The performance of the proposed short form was examined in the validation sample by the use of receiver operation characteristic curves.

Results

Four items which were able to discriminate among individuals with more autism traits were deemed sufficient for use in the short form. The values of the area under the receiver operating characteristic curve for a clinical diagnosis of ASD was .95 (previous validity) and .72 (predictive validity).

Conclusions

The proposed short form with 4 out of the original 17 items from A-TAC, showed excellent previous validity while the predictive validity was fair. The validity of the short form was in agreement with previous validations of the full ASD domain. The short form can be a valuable screening instrument in primary care settings in order to identify individuals in need for further assessment and for use in epidemiological studies.
From prospective clinical trial to reducing social inequalities in health: The DESSEIN trial, concept and design of a multidisciplinary study in precarious patients with breast cancer
Authors: Ngô Charlotte , Dinut Aurélia , Bochaton Audrey , Charreire Hélène , Desprès Caroline , Baffert Sandrine , Lécuru Fabrice , Chatellier Gilles
Published: November 2019

Background

In France during the last 15 years, precariousness among women has increased. In breast cancer, precariousness has been associated with an increase in mortality, but the links between precariousness, stage at diagnosis and care pathway are little explored. Our study aims to evaluate the impact of precariousness on care pathways, treatment and recovery phase according to a multidisciplinary analysis.

Methods and design

Comparative prospective observational multicenter study of exposed / unexposed category. Patients with breast cancer are recruited in the Ile de France area. Three scores are used to identify precarious patients. Precarious patients are matched to non-precarious patients by age group. Questionnaires are distributed to patients at different times of care. The main objective is to compare the stage of the disease at diagnosis between two groups. The secondary objectives are: comparison of socio-economic and geographical characteristics, direct and indirect costs, personal trajectories of care and health. Analysis include multidisciplinary approaches. A geographical information systems method will evaluate the accessibility to health facilities and the characteristics of the places of residence of the patients. An anthropological analysis will be conducted through observation of consultations and semi-directed interviews with patients. These methods will allow to analyze the diagnostic and therapeutic routes, placing it in a life history and an economic, socio-cultural and health environment. The economic analysis will include a comparison of direct, indirect costs and out-off pocket costs, from the patient’s point of view and from the societal perspective.

Discussion

Conducted in a clinical setting and coupled with a qualitative study, this study will provide a better understanding of how contextual factors, combined with individual factors, can influence the course of health and thus the stage of the disease at diagnosis. The multidisciplinary approach, involving clinicians, geographers, an anthropologist, an economist and a health epidemiologist, will allow a multidimensional approach to the impact of precariousness on breast cancer.

Trial registration

ClinicalTrials.gov Identifier: NCT02948478 registered October 28, 2016. ID RCB: 2016-A00589–42. protocol version: 2.1. decembre 13, 2018.
A systematic review of parent based programs to prevent or reduce alcohol consumption in adolescents
Authors: Hurley Erin , Dietrich Timo , Rundle-Thiele Sharyn
Published: November 2019

Background

Adolescent alcohol consumption is an issue of ongoing concern and programs targeting parents have been identified as an important component in minimizing and preventing alcohol related harm in adolescents. This paper aims to evaluate existing parent based alcohol education programs with a focus on understanding parent specific outcomes including parental attitudes, parent-child communication, alcohol specific rule setting and parental monitoring; study quality, the extent of stakeholder engagement in program design and the level of theory application.

Method

A systematic review of electronic databases EBSCO, Emerald, ProQuest, PubMed, Ovid, ScienceDirect, Taylor and Francis and Web of Science was conducted from database inception to August 2019. A total of 4288 unique records were retrieved from the eight databases. Studies were included if they evaluated school based alcohol education programs that included a parent component and detailed outcome measures associated with parent data. The methodological quality of the included studies was assessed using the Effective Public Health Practice Project (EPHPP) quality assessment tool.

Results

In total 17 studies qualified for assessment, detailing 13 individual parent programs. Of these, ten programs demonstrated positive effects in at least one parent reported outcome measure. Stakeholder engagement during the design of programs was lacking with the majority of programs. One third of the programs did not report theory use and when theory was used reporting was weak with three programs applying theory, five testing theory and none building theory. According to the EPHPP tool, overall ten programs were rated as weak, three as moderate and none as strong.

Conclusion

Future studies are recommended to further enhance the effectiveness of parental programs by improving study quality, increasing stakeholder engagement and increasing the level of theory application and reporting.
Health and educational aspirations in adolescence: a longitudinal study in Finland
Authors: Dobewall Henrik , Lindfors Pirjo , Karvonen Sakari , Koivusilta Leena , Vainikainen Mari-Pauliina , Hotulainen Risto , Rimpelä Arja
Published: November 2019

Background

The health selection hypothesis suggests that poor health leads to low educational attainment during the life course. Adolescence is an important period as poor health might prevent students from making the best educational choices. We test if health in adolescence is associated with educational aspirations and whether these associations persist over and above sociodemographic background and academic achievement.

Methods

Using classroom surveys, a cohort of students (n = 5.614) from the Helsinki Metropolitan Region was followed from the 7th (12–13 years,) up to the 9th grade (15–16 years) when the choice between the academic and the vocational track is made in Finland. Health factors (Strengths and Difficulties Questionnaire (SDQ), self-rated health, daily health complaints, and long-term illness and medicine prescribed) and sociodemographic background were self-reported by the students. Students’ educational aspirations (applying for academic versus vocational track, or both) and their academic achievement were obtained from the Joint Application Registry held by the Finnish National Agency for Education. We conducted multilevel multinomial logistic regression analyses, taking into account that students are clustered within schools.

Results

All studied health factors were associated with adolescents’ educational aspirations. For the SDQ, daily health complaints, and self-rated health these associations persisted over and above sociodemographic background and academic achievement. Students with better health in adolescence were more likely to apply for the academic track, and those who were less healthy were more likely to apply for the vocational track. The health in the group of those students who had applied for both educational tracks was in between. Inconsistent results were observed for long-term illness. We also found robust associations between educational aspirations and worsening health from grade 7 to grade 9.

Conclusions

Our findings show that selection by health factors to different educational trajectories takes place at early teenage much before adolescents choose their educational track, thus supporting the health selection hypothesis in the creation of socioeconomic health inequalities. Our findings also show the importance of adolescence in this process. More studies are needed to reveal which measures would be effective in helping students with poor health to achieve their full educational potential.
Participatory learning and action to address type 2 diabetes in rural Bangladesh: a qualitative process evaluation
Authors: Morrison Joanna , Akter Kohenour , Jennings Hannah Maria , Nahar Tasmin , Kuddus Abdul , Shaha Sanjit Kumer , Ahmed Naveed , King Carina , Haghparast-Bidgoli Hassan , Costello Anthony , Khan A. K. Azad , Azad Kishwar , Fottrell Edward
Published: November 2019

Background

Diabetes is 7th largest cause of death worldwide, and prevalence is increasing rapidly in low-and middle-income countries. There is an urgent need to develop and test interventions to prevent and control diabetes and develop the theory about how such interventions can be effective. We conducted a participatory learning and action (PLA) intervention with community groups in rural Bangladesh which was evaluated through a cluster randomised controlled trial. There was a large reduction in the combined prevalence of type 2 diabetes and intermediate hyperglycaemia in the PLA group compared with the control group. We present findings from qualitative process evaluation research to explore how this intervention was effective.

Methods

We conducted group interviews and focus group discussions using photovoice with purposively sampled group attenders and non-attenders, and intervention implementers. Data were collected before the trial analysis. We used inductive content analysis to generate theory from the data.

Results

The intervention increased the health literacy of individuals and communities - developing their knowledge, capacity and self-confidence to enact healthy behaviours. Community, household and individual capacity increased through social support and social networks, which then created an enabling community context, further strengthening agency and enabling community action. This increased opportunities for healthy behaviour. Community actions addressed lack of awareness about diabetes, gendered barriers to physical activity and lack of access to blood glucose testing. The interaction between the individual, household, and community contexts amplified change, and yet there was limited engagement with macro level, or ‘state’, barriers to healthy behaviour.

Conclusions

The participatory approach enabled groups to analyse how context affected their ability to have healthy behaviours and participants engaged with issues as a community in the ways that they felt comfortable. We suggest measuring health literacy and social networks in future interventions and recommend specific capacity strengthening to develop public accountability mechanisms and health systems strengthening to complement community-based interventions.

Trial registration

Registered at ISRCTN on 30th March 2016 (Retrospectively Registered) Registration number: ISRCTN41083256.
Antimicrobial activity and pH measurement of calcium silicate cements versus new bioactive resin composite restorative material
Authors: ElReash Ashraf Abou , Hamama Hamdi , Eldars Waleed , Lingwei Gong , Zaen El-Din Ahmed M. , Xiaoli Xie
Published: November 2019

Background

The purpose of this in vitro study is to compare the antimicrobial effect and pH of two calcium silicate cements Mineral trioxide aggregate high plasticity (Angelus PR, Brazil) and iRoot BP Plus (BioCeramix Inc., Vancouver, BC, Canada) and new bioactive restorative resin composite restorative material (ACTIVA, MA, Pulpdent, USA) against aerobic bacteria, strictly anaerobic bacteria and a yeast by using an agar diffusion test.

Methods

The materials were tested immediately after manipulation and were applied to the agar plates. Sodium hypochlorite (NaOCl) 5.25% was used as a positive control group. The dry filter paper acted as a negative control group for this study. The size of the inhibition zone for each material was measured after 12, 24 and 48 h. At the time of pH measurement; materials were prepared, crushed then dispersed in distilled water.

Results

The one-way Anova test revealed that iRoot BP Plus significantly showed superior antimicrobial efficacy compared to MTA-HP against the following species; Staphylococcus aureus, Streptococcus mutans, Enterococcus faecalis, Enterococcus faecium, Peptostreptococcus anaerobius and Candida albicans (P < 0.05). All of the tested materials did not show any antimicrobial effect against Porphyromonas gingivalis and Actinomyces israelii. The new bioactive resin composite material (ACTIVA) showed the least antimicrobial activity against the previously mentioned microorganisms except E. faecalis. NaOCl significantly showed the highest antimicrobial activity among the test group (P < 0.05). iRoot BP Plus was more alkaline (pH 12.1 ± 0.14/ 11.9 ± 0.25) in comparison to MTA-HP (pH 11.6 ± 0.16/ 11.2 ± 0.10) while ACTIVA was slightly acidic (pH 5.4 ± 0.09/ 6.5 ± 0.08).

Conclusions

According to the findings of this study, it was concluded that calcium silicate- based cements showed a potential antimicrobial activity mainly due to its high alkalinity. The new bioactive resin composite restorative material exhibits less antimicrobial activity due to its resinous ingredients and slightly acidic nature. Antimicrobial effect of calcium silicate cements against strictly anaerobic bacterial species is still questionable.
Aspirin for primary prevention of cardiovascular disease: a meta-analysis with a particular focus on subgroups
Authors: Gelbenegger Georg , Postula Marek , Pecen Ladislav , Halvorsen Sigrun , Lesiak Maciej , Schoergenhofer Christian , Jilma Bernd , Hengstenberg Christian , Siller-Matula Jolanta M.
Published: November 2019

Background

The role of aspirin in primary prevention of cardiovascular disease (CVD) remains unclear. We aimed to investigate the benefit-risk ratio of aspirin for primary prevention of CVD with a particular focus on subgroups.

Methods

Randomized controlled trials comparing the effects of aspirin for primary prevention of CVD versus control and including at least 1000 patients were eligible for this meta-analysis. The primary efficacy outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, major adverse cardiovascular events (MACE), myocardial infarction, ischemic stroke, and net clinical benefit. The primary safety outcome was major bleeding. Subgroup analyses involving sex, concomitant statin treatment, diabetes, and smoking were performed.

Results

Thirteen randomized controlled trials comprising 164,225 patients were included. The risk of all-cause and cardiovascular mortality was similar for aspirin and control groups (RR 0.98; 95% CI, 0.93–1.02; RR 0.99; 95% CI, 0.90–1.08; respectively). Aspirin reduced the relative risk (RRR) of major adverse cardiovascular events (MACE) by 9% (RR 0.91; 95% CI, 0.86–0.95), myocardial infarction by 14% (RR 0.86; 95% CI, 0.77–0.95), and ischemic stroke by 10% (RR 0.90; 95% CI, 0.82–0.99), but was associated with a 46% relative risk increase of major bleeding events (RR 1.46; 95% CI, 1.30–1.64) compared with controls. Aspirin use did not translate into a net clinical benefit adjusted for event-associated mortality risk (mean 0.034%; 95% CI, − 0.18 to 0.25%). There was an interaction for aspirin effect in three patient subgroups: (i) in patients under statin treatment, aspirin was associated with a 12% RRR of MACE (RR 0.88; 95% CI, 0.80–0.96), and this effect was lacking in the no-statin group; (ii) in non-smokers, aspirin was associated with a 10% RRR of MACE (RR 0.90; 95% CI, 0.82–0.99), and this effect was not present in smokers; and (iii) in males, aspirin use resulted in a 11% RRR of MACE (RR 0.89; 95% CI, 0.83–0.95), with a non-significant effect in females.

Conclusions

Aspirin use does not reduce all-cause or cardiovascular mortality and results in an insufficient benefit-risk ratio for CVD primary prevention. Non-smokers, patients treated with statins, and males had the greatest risk reduction of MACE across subgroups.

Systematic review registration

PROSPERO CRD42019118474.
A 3-circular RNA signature as a noninvasive biomarker for diagnosis of colorectal cancer
Authors: Ye Dao-xiong , Wang Si-si , Huang Ying , Chi Pan
Published: November 2019

Background

Circular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and progression of cancer. Emerging studies also shows that circRNAs may function as potential markers for cancer diagnosis and treatment. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed.

Methods

CircRNA microarray was performed to detect the differentially expressed circRNAs in eight plasma samples, including four colorectal cancer (CRC) and four normal samples. Besides, the results of microarray were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, ROC curve evaluation was performed to calculate the diagnostic value of significantly dysregulated circRNAs. In order to predict the potential mechanism of the significant circRNAs, circRNA–miRNA–mRNA network was constructed based on the TargetScan, miRTarBase and MIRDB database, as well as CircInteractome online software. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to further predict the function of meaningful circRNAs.

Results

Totally three differentially expressed circRNAs were identified in CRC plasma compared to normal plasma by circRNA microarray analysis, and the results was validated by qRT-PCR. Hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445 were identified and ROC curves analysis was used to calculate the single and joint diagnostic value. Furthermore, GO and KEGG analyses revealed that functions were mainly cancer-related, which indicated that the circRNAs were meaningfully associated with CRC cell proliferation and metastasis.

Conclusion

In conclusion, we have identified three circRNAs that are dysregulated in CRC plasma, including hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445. ROC curves showed that these circRNAs might have diagnostic value for colorectal cancer. Furthermore, bioinformatics analysis indicated that the above-mentioned circRNAs might be involved in the development of CRC.
Does the inflammatory potential of diet affect disease activity in patients with inflammatory bowel disease?
Authors: Mirmiran Parvin , Moslehi Nazanin , Morshedzadeh Nava , Shivappa Nitin , Hébert James R. , Farsi Farnaz , Daryani Naser Ebrahimi
Published: November 2019

Background

Diet is an important modulator of inflammation, which is associated with inflammatory bowel disease (IBD). In this study, we examined whether the inflammatory properties of diets are associated with disease activity in patients with IBD.

Methods

A cross-sectional study was conducted on 143 IBD patients, including 32 patients with Crohn’s disease (CD) and 111 patients with ulcerative colitis (UC). Dietary intakes were assessed by a valid 168-item food frequency questionnaire (FFQ). The inflammatory potential of the diet was assessed by calculating the two scores of Dietary Inflammatory Index (DII®), and the Empirical Dietary Inflammatory Pattern (EDIP), and CD and UC disease activity were determined by the Crohn’s disease activity index (CDAI) and the Mayo score, respectively. Associations of the inflammatory indices as median and as tertiles with disease activity were analyzed using logistic regression in a univariate model and after adjusting for total energy intake (continuous), type of disease (CD and UC) and drug consumption (no drugs, single drug, and multiple drugs).

Results

Sixty-four IBD patients (44.8%) in this study had active disease.The DII® score and the EDIP did not differ significantly between active and inactive patients (− 1.45 ± 1.04 vs.− 1.20 ± 1.24; 0.56 ± 0.22 vs. 0.53 ± 0.28, respectively). After adjusting for energy intake, drug use, and IBD type, the odds (95%CIs) of active disease among patients in tertile 3 compared to those in tertile 1 were 0.84 (0.32–2.17) for DII and 1.50 (0.61–3.72) for EDIP; neither of which were statistically significantly different from the rates in tertile 1.

Conclusions

Although point estimates were in the expected direction of increased risk, the inflammatory potential of diet, assessed using DII or EDIP, was not associated with severity of disease in IBD patients. Whether diet-related inflammation affects disease activity in patients with IBD deserves further investigations.
Overcoming a travel burden to high-volume centers for treatment of retroperitoneal sarcomas is associated with improved survival
Authors: Schmitz Robin , Adam Mohamed A. , Blazer Dan G.
Published: November 2019

Background

Guidelines recommend treatment of retroperitoneal sarcomas (RPS) at high-volume centers. However, high-volume centers may not be accessible locally. This national study compared outcomes of RPS resection between local low-volume centers and more distant high-volume centers.

Methods

Patients treated for RPS were identified from the National Cancer Database (1998–2012). Travel distance and annual hospital volume were divided into quartiles. Two groups were identified: (1) short travel to low-volume hospitals (ST/LV), (2) long travel to high-volume hospitals (LT/HV). Outcomes were adjusted for clinical, tumor, and treatment characteristics.

Results

Two thousand five hundred ninety-nine patients met the inclusion criteria. The LT/HV cohort was younger and more often white (p < 0.01). The LT/HV group had more comorbidities, higher tumor grade, and more often radical resections and radiotherapy (all p < 0.05). The ST/LV group underwent significantly more R2 resections (4.4% vs. 2.6%, p = 0.003). Thirty-day mortality was significantly lower in the LT/HV group (1.2% vs. 2.8%, p = 0.0026). Five-year survival was better among the LT/HV group (63% vs. 53%, p < 0.0001). After adjustment, the LT/HV group had a 27% improvement in overall survival (HR 0.73, p = 0.0009).

Conclusions

This national study suggests that traveling to high-volume centers for the treatment of RPS confers a significant short-term and long-term survival advantage, supporting centralized care for RPS.
Detecting compensatory movements of stroke survivors using pressure distribution data and machine learning algorithms
Authors: Cai Siqi , Li Guofeng , Zhang Xiaoya , Huang Shuangyuan , Zheng Haiqing , Ma Ke , Xie Longhan
Published: November 2019

Background

Compensatory movements are commonly employed by stroke survivors during seated reaching and may have negative effects on their long-term recovery. Detecting compensation is useful for coaching the patient to reduce compensatory trunk movements and improving the motor function of the paretic arm. Sensor-based and camera-based systems have been developed to detect compensatory movements, but they still have some limitations, such as causing object obstructions, requiring complex setups and raising privacy concerns. To overcome these drawbacks, this paper proposes a compensatory movement detection system based on pressure distribution data and is unobtrusive, simple and practical. Machine learning algorithms were applied to classify compensatory movements automatically. Therefore, the purpose of this study was to develop and test a pressure distribution-based system for the automatic detection of compensation movements of stroke survivors using machine learning algorithms.

Methods

Eight stroke survivors performed three types of reaching tasks (back-and-forth, side-to-side, and up-and-down reaching tasks) with both the healthy side and the affected side. The pressure distribution data were recorded, and five features were extracted for classification. The k-nearest neighbor (k-NN) and support vector machine (SVM) algorithms were applied to detect and categorize the compensatory movements. The surface electromyography (sEMG) signals of nine trunk muscles were acquired to provide a detailed description and explanation of compensatory movements.

Results

Cross-validation yielded high classification accuracies (F1-score>0.95) for both the k-NN and SVM classifiers in detecting compensation movements during all the reaching tasks. In detail, an excellent performance was achieved in discriminating between compensation and noncompensation (NC) movements, with an average F1-score of 0.993. For the multiclass classification of compensatory movement patterns, an average F1-score of 0.981 was achieved in recognizing the NC, trunk lean-forward (TLF), trunk rotation (TR) and shoulder elevation (SE) movements.

Conclusions

Good classification performance in detecting and categorizing compensatory movements validated the feasibility of the proposed pressure distribution-based system. Reliable classification accuracy achieved by the machine learning algorithms indicated the potential to monitor compensation movements automatically by using the pressure distribution-based system when stroke survivors perform seated reaching tasks.
Implementation of a behavioral medicine approach in physiotherapy: a process evaluation of facilitation methods
Authors: Fritz Johanna , Wallin Lars , Söderlund Anne , Almqvist Lena , Sandborgh Maria
Published: November 2019

Background

In a quasi-experimental study, facilitation was used to support implementation of the behavioral medicine approach in physiotherapy. The facilitation consisted of an individually tailored multifaceted intervention including outreach visits, peer coaching, educational materials, individual goal-setting, video feedback, self-monitoring in a diary, manager support, and information leaflets to patients. A behavioral medicine approach implies a focus on health related behavior change. Clinical behavioral change was initiated but not maintained among the participating physiotherapists. To explain these findings, a deeper understanding of the implementation process is necessary. The aim was therefore to explore the impact mechanisms in the implementation of a behavioral medicine approach in physiotherapy by examining dose, reach, and participant experiences.

Methods

An explorative mixed-methods design was used as a part of a quasi-experimental trial. Twenty four physiotherapists working in primary health care were included in the quasi-experimental trial, and all physiotherapists in the experimental group (n = 15) were included in the current study. A facilitation intervention based mainly on social cognitive theory was tested during a 6-month period. Data were collected during and after the implementation period by self-reports of time allocation regarding participation in different implementation methods, documentation of individual goals, ranking of the most important implementation methods, and semi-structured interviews. Descriptive statistical methods and inductive content analysis were used.

Results

The physiotherapists participated most frequently in the following implementation methods: outreach visits, peer coaching, educational materials, and individual goal-setting. They also considered these methods to be the most important for implementation, contributing to support for learning, practice, memory, emotions, self-management, and time management. However, time management support from the manager was lacking.

Conclusions

The findings indicate that different mechanisms govern the initiation and maintenance of clinical behavior change. The impact mechanisms for initiation of clinical behavior change refers to the use of externally initiated multiple methods, such as feedback on practice, time management, and extrinsic motivation. The lack of self-regulation capability, intrinsic motivation, and continued support after the implementation intervention period were interpreted as possible mechanisms for the failure of maintaining the behavioral change over time.
Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective
Authors: Beerepoot Shanice , Nierkens Stefan , Boelens Jaap Jan , Lindemans Caroline , Bugiani Marianna , Wolf Nicole I.
Published: November 2019

Metachromatic leukodystrophy (MLD) is an autosomal recessively inherited metabolic disease characterized by deficient activity of the lysosomal enzyme arylsulfatase A. Its deficiency results in accumulation of sulfatides in neural and visceral tissues, and causes demyelination of the central and peripheral nervous system. This leads to a broad range of neurological symptoms and eventually premature death. In asymptomatic patients with juvenile and adult MLD, treatment with allogeneic hematopoietic stem cell transplantation (HCT) provides a symptomatic and survival benefit. However, this treatment mainly impacts brain white matter, whereas the peripheral neuropathy shows no or only limited response. Data about the impact of peripheral neuropathy in MLD patients are currently lacking, although in our experience peripheral neuropathy causes significant morbidity due to neuropathic pain, foot deformities and neurogenic bladder disturbances. Besides, the reasons for residual and often progressive peripheral neuropathy after HCT are not fully understood. Preliminary studies suggest that peripheral neuropathy might respond better to gene therapy due to higher enzyme levels achieved than with HCT. However, histopathological and clinical findings also suggest a role of neuroinflammation in the pathology of peripheral neuropathy in MLD. In this literature review, we discuss clinical aspects, pathological findings, distribution of mutations, and treatment approaches in MLD with particular emphasis on peripheral neuropathy. We believe that future therapies need more emphasis on the management of peripheral neuropathy, and additional research is needed to optimize care strategies.
The work, goals, challenges, achievements, and recommendations of orphan medicinal product organizations in India: an interview-based study
Authors: Choudhury Mohua Chakraborty , Saberwal Gayatri
Published: November 2019

Background

Orphan medicinal products (OMPs) are intended for the diagnosis, prevention, management or treatment of rare diseases (RDs). Each RD affects only a small fraction of the population,and therefore, historically, industry hesitated to undertake relevant research and development (R&D). In response, the governments of many countries came up with orphan drug policies and RD policies which were hugely successful in incentivizing companies to do so. In India, in the absence of any such policy until recently, there are very few organizations involved in RD R&D.

Objectives

We wished to understand (i) the OMP Organizations’ (OMPOs’) areas of work and the nature of their work, (ii) their goals, (iii) the challenges they faced and how they were overcoming them, (iv) their achievements, and (v) their recommendations to the government to help their R&D, their success as commercial entities (where applicable), and patients’ access to their products or services.

Results

Ten of the 14 OMPOs are companies, whereas four are not-for-profit organizations. Almost all of the OMPOs are heavily into R&D. Six have already made their products or services available to patients. Four plan to out-license their products after the pre-clinical phase or phase 1 trials, eight plan to cater to patients directly and two of the OMPOs have been established only recently and thus do not yet have any product or service to offer patients. Nine OMPOs import about 90% of the components in the production process, which comprises either capital or recurrent expenditure. For most, locally manufactured alternatives are not available or are of inadequate quality. Most of the OMPOs have had productive collaborations with local or foreign academics or hospitals for R&D, animal efficacy studies, clinical trials or providing services to patients. The main challenges for the OMPOs are the lack of adequate funding, supportive government policies, and a conducive ecosystem.

Conclusions

These OMPOs are pioneers in their respective fields in India, and despite the challenges, have achieved new levels of innovation. With suitable government policies, they could scale up and provide relevant products and services to the large number of RD patients in the country whose medical needs are largely unmet.
Neurofilament light chain is a promising serum biomarker in spinocerebellar ataxia type 3
Authors: Li Quan-Fu , Dong Yi , Yang Lu , Xie Juan-Juan , Ma Yin , Du Yi-Chu , Cheng Hao-Ling , Ni Wang , Wu Zhi-Ying
Published: November 2019

Background

Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of autosomal dominantly inherited spinocerebellar ataxias (SCAs). No validated blood biomarker is available to assess either disease progression or therapeutic response. Neurofilament light chain (NfL) was recently proposed as a serum biomarker for many neurodegenerative disorders. The present study investigated whether NfL was a promising serum biomarker for SCA3.

Methods

Seventeen SCA3 patients and 9 controls were enrolled in cohort A, and 116 SCA3 individuals (preclinical and patients) and 91 controls were recruited as cohort B. We assessed whether serum NfL correlated with cerebrospinal fluid (CSF) NfL in cohort A and correlations between serum NfL levels and clinical features and brain volumes were determined in cohort B. The single-molecule array method was used to measure serum NfL levels. Disease severity was determined using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). Cerebellar and brainstem volumes were assessed using MRI neuroimaging measurements.

Results

Serum/CSF NfL levels in cohort A were elevated in SCA3 patients, and serum and CSF NfL exhibited a significant positive correlation (r = 0.9179, p < 0.0001). Levels of serum NfL in cohort B were significantly higher in preclinical SCA3 (15.03 ± 7.49 vs 6.88 ± 2.72 pg/ mL, p < 0.0001) and manifest SCA3 subjects (37.56 ± 13.47 vs 9.07 ± 6.02 pg/ mL, p < 0.0001) compared to those in controls. Serum NfL concentrations increased from early disease stage to the next stage. Levels of serum NfL in ATXN3 mutation carriers were positively associated with SARA (r = 0.5458, p < 0.0001) and ICARS scores (r = 0.5522, p < 0.0001). Significant negative associations with cerebellar volumes (r = − 0.4217, p = 0.0003) and brainstem volumes (r = − 0.4263, p = 0.0003) were observed. All changes remained significant after adjustment for age and CAG repeat.

Conclusions

Levels of serum NfL were significantly elevated in SCA3 individuals and correlated with disease severity. Serum NfL is a promising serum biomarker of disease onset and progression, and a potential candidate biomarker of treatment response in SCA3.
Molecular cytogenetic analysis and genetic counseling: a case report of eight 46,XX males and a literature review
Authors: Yue Fagui , Zhang Hongguo , Xi Qi , Jiang Yuting , Li Leilei , Liu Ruizhi , Wang Ruixue
Published: November 2019

Background

46,XX male syndrome is a rare disorder that usually causes infertility. This study was established to identify the genetic causes of this condition in a series of 46,XX males through the combined application of cytogenetic and molecular genetic techniques.

Case presentation

We identified eight azoospermic 46,XX males who underwent infertility-related consultations at our center. They all presented normal male phenotypes. In seven of the eight 46,XX males (87.5%), translocation of theSRYgene to the terminal short arm of the X chromosome was clearly involved in their condition, which illustrated that this translocation is the main mechanism of 46,XX sex reversal, in line with previous reports. However, one patient presented a homozygousDAX1mutation (c.498G > A, p.R166R), which was not previously reported inSRY-negative XX males.

Conclusions

We proposed that this synonymousDAX1mutation in case 8 might not be associated with the activation of the male sex-determining pathway, and the male phenotype in this case might be regulated by some unidentified genetic or environmental factors. Hence, the detection of genetic variations associated with sex reversal in critical sex-determining genes should be recommended forSRY-negative XX males. Only after comprehensive cytogenetic and molecular genetic analyses can genetic counseling be offered to 46,XX males.
Prohibitin (PHB) expression is associated with aggressiveness in DLBCL and flavagline-mediated inhibition of cytoplasmic PHB functions induces anti-tumor effects
Authors: Bentayeb Hafidha , Aitamer Marine , Petit Barbara , Dubanet Lydie , Elderwish Sabria , Désaubry Laurent , de Gramont Armand , Raymond Eric , Olivrie Agnès , Abraham Julie , Jauberteau Marie-Odile , Troutaud Danielle
Published: November 2019

Background

Diffuse large B-cell lymphomas (DLBCLs) are aggressive lymphomas accounting for approximately a third of non-Hodgkin lymphomas. Prohibitin 1 (PHB1) and prohibitin 2 (PHB2) are scaffold proteins that promote mitochondria homeostasis and consequently cell survival, but biological functions of cytoplasmic PHBs remain largely unknown in DLBCL.

Methods

PHB expression was analyzed in 82 DLBCL biopsies and five DLBCL cell lines by immunohistochemistry (IHC) and Western blotting. Pharmacological inhibition of PHB using the synthetic flavagline FL3 was realized in vitro to gain insight PHB cellular functions. Effects of FL3 on DLBCL cell line viability, apoptosis, C-Raf-ERK–MNK–eIF4E signaling pathway and eIF4F complex formation and activity were evaluated by XTT assay, annexin V-FITC/PI dual staining and Western blotting respectively. Subcutaneous DLBCL xenograft model in SCID mice was also performed to determine in vivo FL3 effect.

Results

As in DLBCL cell lines, PHB1 and PHB2 were expressed in germinal center B-cell–like (GCB) and activated B-cell–like (ABC) subtypes. In patient samples, high PHB levels were associated with higher serum LDH (PHB1 and PHB2), IPIaa (PHB2), and Ki-67 (PHB2) expression. Higher PHB1 expression tends to be associated with shorter event-free survival (EFS) in patients, especially in male patients. FL3 induced apoptosis of DLBCL cell lines that was associated with inhibition of the ERK-MNK-eIF4E signaling pathway, including aggressive double/triple-hit DLBCL cell lines. This resulted in altered eIF4F complex formation and activity leading to a reduction of Bcl-2 and c-Myc expression levels. Moreover, FL3 strongly downregulated DLBCL cellular levels of Akt protein and AKT mRNA. FL3 antitumor activity was also confirmed in vivo in a murine xenograft model.

Conclusion

Our data indicate that PHB overexpression is associated with markers of tumor aggressiveness in DLBCL, and that targeting PHBs may be a therapeutic option, notably in aggressive subtypes.
SP600125 enhances C-2-induced cell death by the switch from autophagy to apoptosis in bladder cancer cells
Authors: Yu Haiyang , Wu Chun-Li , Wang Xiangyu , Ban Qianhong , Quan Chunhua , Liu Mengbo , Dong Hangqi , Li Jinfeng , Kim Gi-Young , Choi Yung Hyun , Wang Zhenya , Jin Cheng-Yun
Published: November 2019

Background

A natural compound Jaspine B and its derivative possess potential anti-cancer activities; However, little is known about the underlying mechanism. Here, the role of a new autophagy inducer Jaspine B derivative C-2 in suppressing bladder cancer cells was researched in vitro and in vivo.

Methods

The underlying mechanisms and anticancer effect of C-2 in bladder cancer cells were investigated by MTT, western blotting, immunoprecipitation and immunofluorescence assays. The key signaling components were investigated by using pharmacological inhibitors or specific siRNAs. In vivo, we designed a C-2 and SP600125 combination experiment to verify the effectiveness of compound.

Results

C-2 exhibits cytotoxic effect on bladder cancer cells, and JNK activated by C-2 triggers autophagy and up-regulates SQSTM1/p62 proteins, contributing to activation of Nrf2 pathway. Utilization of JNK inhibitor SP600125 or knockdown of JNK by siRNA potentiate the cytotoxicity of C-2 through down-regulation of p62 and LC3II proteins and up-regulation of active-Caspase3 proteins, enhance the cell death effect, facilitating the switch from autophagy to apoptosis. In vivo study, C-2 suppresses tumor growth in a xenograft mouse model of EJ cells without observed toxicity. Combined treatment with SP600125 further enhances tumor inhibition of C-2 associated with enhanced activation of caspase3 and reduction of autophagy.

Conclusions

It reveals a series of molecular mechanisms about SP600125 potentiate the cytotoxicity and tumor inhibition of C-2 in bladder cancer cells through promoting C-2-induced apoptosis, expecting it provides research basis and theoretical support for new drugs development.