bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe sleep disturbance is associated with executive function impairment in patients with first-episode, treatment-naïve major depressive disorders
Authors: Cui Feihuan , Liu Qi , Lv Xiaozhen , Leonhart Rainer , Tian Hongjun , Wei Jing , Zhang Kerang , Zhu Gang , Chen Qiaoling , Wang Gang , Wang Xueyi , Zhang Nan , Huang Yu , Si Tianmei , Yu Xin
Published: April 2021

Background

Sleep disturbance and executive function impairment are common in patients with major depressive disorder (MDD), though the relationship between the two remains unclear. We investigated this association in first-episode, treatment-naïve patients with MDD.

Methods

We analyzed data from 242 patients with MDD. We divided the patients into 2 groups based on sleep disturbance severity and compared the executive function odds ratios between the groups.

Results

A total of 121 pairs of patients were matched (age 39.4 ± 10.1, 70.2% female). After propensity score matching, the odds ratios for cognitive impairment in patients with MDD and severe sleep disturbance were 1.922 (1.068–3.459, P = 0.029, q = 0.044) in executive functioning; 2.023 (1.211–3.379, P = 0.007, q = 0.021) in executive shifting.

Conclusions

Sleep disturbance is associated with executive functioning impairment in first-episode, treatment-naïve patients with MDD. Severe sleep disturbance can be a marker and aid in recognizing executive function impairment in patients with first-episode treatment-naïve MDD. Severe sleep disturbance can be a potential modifiable factor to improve executive function in MDD, as well as an effective measurement to improve cognition for sleep symptom management that should be enforced at initial treatment of first-episode MDD. Further study is required to confirm our results.

Trial registration

ClinicalTrials.gov: NCT02023567; registration date: December 2013.
Correction to: Implementation, efficacy, costs and processes of inpatient equivalent hometreatment in German mental health care (AKtiV): protocol of a mixed-method, participatory, quasi-experimental trial
Authors: Baumgardt Johanna , Schwarz Julian , Bechdolf Andreas , Nikolaidis Konstantinos , Heinze Martin , Hamann Johannes , Holzke Martin , Längle Gerhard , Richter Janina , Brieger Peter , Kilian Reinhold , Timm Jürgen , Hirschmeier Constance , Von Peter Sebastian , Weinmann Stefan
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
A systematic review of the latent structure of the Center for Epidemiologic Studies Depression Scale (CES-D) amongst adolescents
Authors: Blodgett Joanna M. , Lachance Chantelle C. , Stubbs Brendon , Co Melissa , Wu Yu-Tzu , Prina Matthew , Tsang Vivian W. L. , Cosco Theodore D.
Published: April 2021

Background

The Centre for Epidemiologic Studies Depression Scale (CES-D) is a commonly used psychometric scale of depression. A four-factor structure (depressed affect, positive affect, somatic symptoms, and interpersonal difficulties) was initially identified in an American sample aged 18 to 65. Despite emerging evidence, a latent structure has not been established in adolescents. This review aimed to investigate the factor structure of the CES-D in adolescents.

Methods

We searched Web of Science, PsychINFO and Scopus and included peer-reviewed, original studies assessing the factor structure of the 20-item CES-D in adolescents aged ≤18. Two independent researchers screened results and extracted data.

Results

Thirteen studies met the inclusion criteria and were primarily from school-based samples in the USA or Asia. Studies that conducted confirmatory factor analysis (CFA; n = 9) reported a four-factor structure consistent with the original factor structure; these studies were primarily USA-based. Conversely, studies that conducted exploratory factor analysis (EFA) reported distinct two or three factor structures (n = 4) and were primarily based in Asia.

Limitations

Studies in a non-English language and those that included individuals aged > 18 years were excluded. Ethnic or cultural differences as well as different analytical methods impacted generalisability of results. The use of CFA as the primary analysis may have biased towards a four-factor structure.

Conclusions

A four-factor CES-D structure was an appropriate fit for adolescents in Western countries; further research is required to determine the fit in in Asian countries. This has important implications for clinical use of the scale. Future research should consider how cultural differences shape the experience of depression in adolescents.
The impacts of collaboration between local health care and non-health care organizations and factors shaping how they work: a systematic review of reviews
Authors: Alderwick Hugh , Hutchings Andrew , Briggs Adam , Mays Nicholas
Published: April 2021

Background

Policymakers in many countries promote collaboration between health care organizations and other sectors as a route to improving population health. Local collaborations have been developed for decades. Yet little is known about the impact of cross-sector collaboration on health and health equity.

Methods

We carried out a systematic review of reviews to synthesize evidence on the health impacts of collaboration between local health care and non-health care organizations, and to understand the factors affecting how these partnerships functioned. We searched four databases and included 36 studies (reviews) in our review. We extracted data from these studies and used Nvivo 12 to help categorize the data. We assessed risk of bias in the studies using standardized tools. We used a narrative approach to synthesizing and reporting the data.

Results

The 36 studies we reviewed included evidence on varying forms of collaboration in diverse contexts. Some studies included data on collaborations with broad population health goals, such as preventing disease and reducing health inequalities. Others focused on collaborations with a narrower focus, such as better integration between health care and social services. Overall, there is little convincing evidence to suggest that collaboration between local health care and non-health care organizations improves health outcomes. Evidence of impact on health services is mixed. And evidence of impact on resource use and spending are limited and mixed. Despite this, many studies report on factors associated with better or worse collaboration. We grouped these into five domains: motivation and purpose, relationships and cultures, resources and capabilities, governance and leadership, and external factors. But data linking factors in these domains to collaboration outcomes is sparse.

Conclusions

In theory, collaboration between local health care and non-health care organizations might contribute to better population health. But we know little about which kinds of collaborations work, for whom, and in what contexts. The benefits of collaboration may be hard to deliver, hard to measure, and overestimated by policymakers. Ultimately, local collaborations should be understood within their macro-level political and economic context, and as one component within a wider system of factors and interventions interacting to shape population health.
Impact of social capital, sex and education on the utilization of public health services: a cross sectional study based on the China migrant dynamic survey
Authors: Yang Zhen , Jiang Cheng-hua
Published: April 2021

Background

China is making efforts to promote the equalization of National Essential Public Health Services (NEPHS) for internal migrants. Studies have demonstrated that the impacts of social capital on health services are different among subgroups of people. Clarifying these differences will help China accurately promote the equalization of NEPHS for the internal migrants and provide reference for other countries.

Methods

Data from the China Migrant Dynamic Survey of 2017, involving 130,642 migrants in 31 provinces were used to clarify the complex relationship between social capital and the utilization of NEPHS. Social capital was divided into regional cognitive social capital (RCSC), regional structural social capital (RSSC), individual cognitive social capital (ICSC), and individual structural social capital (ISSC). Then, multi-level logistic regression was conducted to analyze their impacts on the utilization of NEPHS of the migrants, and whether such impacts are moderated by sex and education.

Results

(1) There are significant differences in the levels of CSC, SSC, and NEPHS utilization between different sexs and educational subgroups of the migrants, among which the educational difference is more prominent. (2) An interaction exists between the levels and dimensions of social capital and NEPHS projects. Also, the impact of SSC on NEPHS is always greater than that of CSC at the same level. (3) The effects of RCSC, RSSC, ICSC, and ISSC on NEPHS utilization by migrants are not moderated by sex. However, a high education could weaken the relationship between RCSC and health education, ISSC and health education, and RSSC and health records but strengthen the correlation between RSSC and health education.

Conclusion

Social capital plays an important role in the access of migrants to NEPHS. Governments should vigorously promote the construction of regional social capital, encourage migrants to actively participate in community activities, especially pay attention to the enhancement of the migrants with low SES to the destination identity.
Effects of a web-based rehabilitation aftercare on subjective health, work ability and motivation: a partially randomized controlled trial
Authors: Jekauc Darko , Rayling Sabine , Klopp Sara , Schmidt Detlef , Rittmann Lena-Marie , Fritsch Julian
Published: April 2021

Background

Rehabilitation is seen as crucial in dealing with the demographic change in many European countries. In Germany, for example, after having stayed in a rehabilitation center, patients have the possibility to participate in aftercare programs aimed at promoting long-term health behaviour. Despite the relevance of follow-up support for patients’ long-term health and work ability, participation rates in aftercare programs are quite low. Here, web-based aftercare programs can be a viable alternative to the traditional face-to-face programs due to their flexibility in time and location. This research project aims to use quantitative and qualitative methods to gain more insight into the potential of web-based aftercare programs.

Methods

The goal is to recruit up to 1150 patients at baseline in five rehabilitation centers across Germany. For ethical reasons, partially randomized experimental study design is used to quantitatively assess the effectiveness of web-based aftercare programs. All patients are offered the traditional face-to-face aftercare treatment (IRENA). When patients deny to participate in traditional face-to-face aftercare, they are randomly distributed into either web-based aftercare (digIRENA) or a control group. In all three groups, the SF-12, which measures subjective health, and the WAI, which measures working ability, will be used at baseline, 13 weeks, 26 weeks and 43 weeks after the patients have left the rehabilitation center. BREQ-2, which measures motivation, is used only in the traditional aftercare group and the web-based aftercare group. A multivariate analysis of variance with repeated measurement and latent growth curve models will be used to compare the development of the variables in the three groups. For the qualitative part of the study, interviews with patients and therapists will be conducted to shed light on the applicability, acceptance, and usability of web-based aftercare programs.

Discussion

This study may provide valuable insight into the potential of web-based rehabilitation aftercare programs as a way to supplement traditional face-to-face programs. This seems particularly promising if it can manage to reach those patients who do not currently participate in traditional face-to-face rehabilitation aftercare programs due to time and location constraints.

Trial registration

The trial has been registered at the German Register of Clinical Studies (DRKS) with the registration number:DRKS00022467.
Evaluating the long-term efficacy and effectiveness of Viscocanalostomy and combined phacoemulsification with Viscocanalostomy in the treatment of patients with uveitic glaucoma: 5-year follow up data
Authors: Salloukh Adonis El , Ansari Abdus Samad , Chiu Alexander , Mathews Divya
Published: April 2021

Background

Uveitic glaucoma commonly leads to a more intense optic nerve damage than other types of glaucoma, causing glaucomatous optic nerves and visual field defects. Anterior uveitis is the most commonly associated risk factor. Surgical intervention is usually indicated when all medical treatment has failed. We report five-year results for 16 eyes of uveitic glaucoma managed with viscocanalostomy (VC)/Phaco viscocanalostomy (PVC).

Methods

Retrospective analysis on all uveitic glaucoma cases meeting a five-year follow up was completed. All patients were managed surgically with either viscocanalostomy (VC) or phacoviscocanalostomy (PVC). Outcomes evaluated included intraocular pressures measurement pre-listing, on day 1, year 1 to year 5. Complete success rate was defined as achieving an intraocular pressure (IOP) lower than 21 mmHg or reduced by 30% without medications, and qualified success was achieved when IOP was lower than 21 mmHg or a reduction in IOP of 30% with topical medical therapy ± Laser goniopuncture (LGP). If further surgeries were required to reduce IOP due to glaucoma progression then they were classified as a failure.

Results

A total of 16 patients with uveitic glaucoma were reviewed. Complete success was seen in 75% of patients at year 1, 50% of patients at year 3 and 19% of patients in year 5. Conversely qualified success was achieved in 94% of patients at year 1, 86% of patients at year 3 and 75% of patients at year 5. In the group of patients requiring further surgery, 50% of patients had previous surgeries, including cataract surgery, trabeculectomy and viscocanalostomy. There was a mean number of 4 pre-operative drops before their primary surgery and a mean drop in eye medications of 1.1 at 5 years follow-up. Success rates were prognostically linked to lower mean number of interventions and lower percentage of previous surgeries.

Conclusion

There remains a significant paucity of information in the utilization of PVC in uveitic glaucoma. The advantage of nonpenetrating glaucoma surgery (NPGS) includes the lack of entry into the anterior chamber and the avoidance of an iridectomy which may reduce intraocular inflammation and postoperative complications. Our study shows that non-penetrating surgery is successful in treating advanced uveitic glaucoma.
Ureteral distal ends combined and inserted into the ileum: a novel anastomotic technique for urinary diversion
Authors: Wang Qi , Tang Liang , Bi Liangkuan , Min Jie , Fang Lu , Sun Wei , Yu Dexin
Published: April 2021

Background

This study aimed to introduce a novel method for ureteroileal anastomosis, explore its clinical effectiveness, observe the incidence of postoperative anastomotic stricture, and compare the postoperative complications with those of other types of ureteroileal anastomosis reported in the literature.

Methods

Both ureters were first anastomosed at their distal ends and then inserted into the proximal end of the ileal loop. A postoperative follow-up analysis was performed to evaluate major complication indicators, including anastomotic stricture, anastomotic leak, and hydroureteronephrosis.

Results

We successfully performed ureteral distal ends anastomosis combined with end-to-end insertion into the ileum for 143 patients. The mean postoperative follow-up lasted 37 months (range: 10–68 months). There was no occurrence of an anastomotic leak. The incidence of anastomotic stricture combined with hydronephrosis, ileal conduit stones, urinary tract infection, and renal dysfunction were 2.1%, 0.7%, 2.1%, and 4.2%, respectively.

Conclusion

Ureteral distal ends combined and inserted into the ileum were simple to perform and helped achieve precise anastomosis with fewer postoperative complications.
Enamel interproximal reduction during treatment with clear aligners: digital planning versus OrthoCAD analysis
Authors: Laganà Giuseppina , Malara Arianna , Lione Roberta , Danesi Carlotta , Meuli Simonetta , Cozza Paola
Published: April 2021

Background

The aim of the study was to compare the amount of interproximal enamel reduction (IPR) provided on ClinCheck software with the amount of IPR carried out by the orthodontist during treatment with clear aligners.

Methods

30 subjects (14 males, 16 females; mean age of 24.53 ± 13.41 years) randomly recruited from the Invisalign account of the Department of Orthodontics at the University of Rome “Tor Vergata” from November 2018 to October 2019, were collected according to the following inclusion criteria: mild to moderate dento-alveolar discrepancy (1.5–6.5 mm); Class I canine and molar relationship; full permanent dentition (excluding third molars); both arches treated only using Comprehensive Package by Invisalign system; treatment plan including IPR. Pre- (T0) and post-treatment (T1) digital models (.stl files), created from an iTero scan, were collected from all selected patients. The OrthoCAD digital software was used to measure tooth mesiodistal width in upper and lower arches before (T0) and at the end of treatment (T1) before any refinement. The widest mesio-distal diameter was measured for each tooth excluding molars by “Diagnostic” OrthoCAD tool. The total amount of IPR performed during treatment was obtained comparing the sum of mesio-distal widths of all measured teeth at T0 and T1. Significant T1–T0 differences were tested with dependent sample t-test (P < 0.05).

Results

In the upper arch, IPR was digitally planned on average for 0.62 mm while in the lower arch was on average for 1.92 mm. As for the amount of enamel actually removed after IPR performing, it was on average 0.62 mm in the maxillary arch. In the mandibular arch, the mean of IPR carried out was 1.93 mm. The difference between planned IPR and performed IPR is described: this difference was on average 0.00 mm in the upper arch and 0.01 in the lower arch.

Conclusions

The amount of enamel removed in vivo corresponded with the amount of IPR planned by the Orthodontist using ClinCheck software.
Associations between a history of sexual abuse and dental anxiety, caries experience and oral hygiene status among adolescents in sub-urban South West Nigeria
Authors: Folayan Morenike Oluwatoyin , El Tantawi Maha , Aly Nourhan M. , Adeniyi Abiola Adetokunbo , Oziegbe Elizabeth , Arowolo Olaniyi , Alade Michael , Mapayi Boladale , Chukwumah Nneka Maureen , Oginni Olakunle , Sam-Agudu Nadia A.
Published: April 2021

Introduction

Sexual and oral health are important areas of focus for adolescent wellbeing. We assessed for the prevalence of sexual abuse among adolescents, oral health factors associated with this history, and investigated whether sexual abuse was a risk indicator for dental anxiety, caries experience and poor oral hygiene.

Methods

This was a cross-sectional study conducted between December 2018 and January 2019 among adolescents 10–19 years old in Ile-Ife, Nigeria. Survey data collected included respondents’ age, sex, and socioeconomic status, oral health risk factors (dental anxiety, frequency of tooth brushing intake of refined carbohydrates in-between-meals, flossing, dental visits, smoking, alcohol intake, use of psychoactive substances), caries experience, oral hygiene status, history of sexual abuse, and sexual risk behaviors (age of sexual debut, history of transactional sex, last sexual act with or without condom, multiple sex partners). Regression models were constructed to determine the association between outcome variables (dental anxiety, presence of caries experience and poor oral hygiene) and explanatory variables (oral health risk factors and history of sexual abuse).

Results

The prevalence of sexual abuse in our cohort was 5.9%: 4.3% among males and 7.9% among females. A history of sexual abuse was associated with alcohol consumption (p = 0.009), cigarette smoking (p = 0.001), and a history of transactional sex (p = 0.01). High/severe dental anxiety was significantly associated with increased odds of a history of sexual abuse (AOR = 1.81; 95% CI 1.10, 2.98), but not with caries experience (AOR = 0.66; 95% CI 0.15, 2.97) nor poor oral hygiene (AOR = 1.68; 95% CI 0.95, 2.96). Dental anxiety was associated with increased odds of alcohol intake (AOR = 1.74; 95% CI 1.19, 2.56), twice daily tooth brushing (AOR = 1.48; 95% CI 1.01, 2.17) and daily consumption of refined carbohydrates in-between-meals (AOR = 2.01; 95% CI 1.60, 2.54). Caries experience was associated with increased odds of using psychoactive substances (AOR = 4.83; 95% CI 1.49, 15.62) and having low socioeconomic status (AOR = 0.40; 95% CI 0.18, 0.92). Poor oral hygiene was associated with increased odds of having middle socioeconomic status (AOR = 1.43; 95% CI 1.05, 1.93) and daily consumption of refined carbohydrates in-between-meals (AOR = 1.38; 95% CI 1.08, 1.78).

Conclusion

Adolescents who are highly dentally anxious need to be screened for a history of sexual abuse to facilitate access to professional care and support.
Examination of resident characteristics associated with interest in primary care and identification of barriers to cross-cultural care
Authors: Abrahams Sara , Kim Eun Ji , Marrast Lyndonna , Uwemedimo Omolara , Conigliaro Joseph , Martinez Johanna
Published: April 2021

Background

There is an increasing shortage of primary care physicians in the U.S. The difficult task of addressing patients’ sociocultural needs is one reason residents do not pursue primary care. However, associations between residents’ perceived barriers to cross-cultural care provision and career interest in primary care have not been investigated.

Objective

We examined residents’ career interest in primary care and associations with resident characteristics and their perceived barriers in providing cross-cultural care.

Methods

We conducted a cross-sectional analysis of a resident survey from the 2018–2019 academic year. We first described residents’ sociodemographic characteristics based on their career interest in primary care (Chi-square test). Our primary outcome was high career interest in primary care. We further examined associations between residents’ characteristics and perceived barriers to cross-cultural care.

Results

The study included 155 family medicine, pediatrics, and internal medicine residents (response rate 68.2%), with 17 expressing high career interest in primary care. There were significant differences in high career interest by race/ethnicity, as Non-White race was associated with high career interest in primary care (p < 0.01). Resident characteristics associated with identifying multiple barriers to cross-cultural care included disadvantaged background, multilingualism, and foreign-born parents (all p-values< 0.05). There were no significant associations between high career interest in primary care and barriers to cross-cultural care.

Conclusion

Residents from diverse racial/ethnic and socioeconomic backgrounds demonstrated higher career interest in primary care and perceived more barriers to cross-cultural care, underscoring the importance of increasing physician workforce diversity to address the primary care shortage and to improve cross-cultural care.
Compared with the monocyte to high-density lipoprotein ratio (MHR) and the neutrophil to lymphocyte ratio (NLR), the neutrophil to high-density lipoprotein ratio (NHR) is more valuable for assessing the inflammatory process in Parkinson’s disease
Authors: Liu Zhu , Fan Qingli , Wu Shizheng , Wan Yaqi , Lei Yancheng
Published: April 2021

Background

The inflammatory response plays essential roles in the pathological process and prognosis of Parkinson’s disease (PD). This research investigated the predictive value of the neutrophil to high-density lipoprotein ratio (NHR), neutrophil to lymphocyte ratio (NLR), and monocyte to high-density lipoprotein ratio (MHR) for PD.

Methods

Patients with PD (n = 98) were divided into three groups according to disease duration: < 6 years (n = 55), 6–10 years (n = 29) and > 10 years (n = 14). Based on the classification system of Hoehn and Yahr, grades 1 ~ 2.5 were considered early-stage PD (n = 44), and grades 3 ~ 5 were considered advanced-stage PD (n = 54). In addition, healthy subjects (n = 98) matched to the above PD patients in the same period were selected as the control group. Differences in the NHR, NLR, MHR and other indicators among the groups were evaluated.

Results

Smoking, drinking, the neutrophil count and the NHR and NLR were remarkably greater and hypertension, index of body mass, the lymphocyte count, and the levels of cholesterol in total, triglycerides, lipoprotein cholesterol with low density and uric acid were sharply lower in the PD group compared with in the control group. Analysis of multifactor logistic regression indicated that the NHR (odds ratio (adjusted OR) = 1.576, 95% CI: 1.053 ~ 2.358, P = 0.027) and NLR (adjusted OR = 1.734, 95% CI: 1.046 ~ 2.876, P = 0.033) were factors of risk for PD, while the MHR was not significantly correlated with PD. The areas under the receiver operating characteristic (ROC) curve (AUCs) for the prediction of PD by the NHR and NLR were 0.654 (95% CI: 0.583 ~ 0.721, P = 0.0001) and 0.69 (95% CI: 0.62 ~ 0.754, P < 0.0001), respectively, and the optimal cutoff values were 1.848 × 109/mmol and 2.62 × 109/mmol. Spearman’s correlation analysis indicated that the NHR was correlated with the disease duration significantly negatively and that the MHR was positively correlated with disease severity.

Conclusions

In summary, the NHR not only has strong predictive value for PD but is also closely related to disease duration. The NHR may be a better prediction for the long-period clinical results in PD patients than the MHR and NLR.

Trial registration

Clinical medical reserach center project of Qinghai Province (2017-SF-L1).
WAPL orchestrates porcine oocyte meiotic progression via control of spindle assembly checkpoint activity
Authors: Zhou Changyin , Miao Yilong , Zhang Xue , Xiong Bo
Published: April 2021

Background

In mitotic cells, WAPL acts as a cohesin release factor to remove cohesin complexes from chromosome arms during prophase to allow the accurate chromosome segregation in anaphase. However, we have recently documented that Wapl exerts a unique meiotic function in the spindle assembly checkpoint (SAC) control through maintaining Bub3 stability during mouse oocyte meiosis I. Whether this noncanonical function is conserved among species is still unknown.

Methods

We applied RNAi-based gene silencing approach to deplete WAPL in porcine oocytes, validating the conserved roles of WAPL in the regulation of SAC activity during mammalian oocyte maturation. We also employed immunostaining, immunoblotting and image quantification analyses to test the WAPL depletion on the meiotic progression, spindle assembly, chromosome alignment and dynamics of SAC protein in porcine oocytes.

Results

We showed that depletion of WAPL resulted in the accelerated meiotic progression by displaying the precocious polar body extrusion and compromised spindle assembly and chromosome alignment. Notably, we observed that the protein level of BUB3 was substantially reduced in WAPL-depleted oocytes, especially at kinetochores.

Conclusions

Collectively, our data demonstrate that WAPL participates in the porcine oocyte meiotic progression through maintenance of BUB3 protein levels and SAC activity. This meiotic function of WAPL in oocytes is highly conserved between pigs and mice.
Interprofessional collaboration and barriers among health and social workers caring for older adults: a Philippine case study
Authors: Moncatar TJ Robinson T. , Nakamura Keiko , Siongco Kathryn Lizbeth L. , Seino Kaoruko , Carlson Rebecca , Canila Carmelita C. , Javier Richard S. , Lorenzo Fely Marilyn E.
Published: April 2021

Background

There is limited information on how the barriers to interprofessional collaboration (IPC) across various professionals, organizations, and care facilities influence the health and welfare of older adults. This study aimed to describe the status of IPC practices among health and social workers providing care for older adults in the Philippines; investigate the perceived barriers to its implementation and perceived effects on geriatric care; and identify possible solutions to address the barriers limiting collaborative practice.

Methods

A case study approach was utilized employing 12 semi-structured in-depth interviews and 29 focus group discussions with care workers from selected primary health care units, public and private hospitals, and nursing homes that are directly involved in geriatric care delivery in two cities in the Philippines. Overall, 174 health and social workers consented to participate in this study. All interviews were audio-recorded and transcribed verbatim. An inductive thematic analysis using NVivo 12® was used to identify and categorize relevant thematic codes.

Results

Interprofessional geriatric care provided by health and social workers was observed to be currently limited to ad hoc communications typically addressing only administrative concerns. This limitation is imposed by a confluence of barriers such as personal values and beliefs, organizational resource constraints, and a silo system care culture which practitioners say negatively influences care delivery. This in turn results in inability of care providers to access adequate care information, as well as delays and renders inaccessible available care provided to vulnerable older adults. Uncoordinated care of older adults also led to reported inefficient duplication and overlap of interventions.

Conclusion

Geriatric care workers fear such barriers may aggravate the increasing unmet needs of older adults. In order to address these potential negative outcomes, establishing a clear and committed system of governance that includes IPC is perceived as necessary to install a cohesive service delivery mechanism and provide holistic care for older adults. Future studies are needed to measure the effects of identified barriers on the potential of IPC to facilitate an integrated health and social service delivery system for the improvement of quality of life of older adults in the Philippines.
Collective reflections on the first cycle of a collaborative learning platform to strengthen rural primary healthcare in Mpumalanga, South Africa
Authors: van der Merwe Maria , D’Ambruoso Lucia , Witter Sophie , Twine Rhian , Mabetha Denny , Hove Jennifer , Byass Peter , Tollman Stephen , Kahn Kathleen ,   the Verbal Autopsy with Participatory Action Research (VAPAR)/Wits/Mpumalanga Department of Health Learning Platform
Published: April 2021

Background

Frontline managers and health service providers are constrained in many contexts from responding to community priorities due to organizational cultures focused on centrally defined outputs and targets. This paper presents an evaluation of the Verbal Autopsy with Participatory Action Research (VAPAR) programme—a collaborative learning platform embedded in the local health system in Mpumalanga, South Africa—for strengthening of rural primary healthcare (PHC) systems. The programme aims to address exclusion from access to health services by generating and acting on research evidence of practical, local relevance.

Methods

Drawing on existing links in the provincial and national health systems and applying rapid, participatory evaluation techniques, we evaluated the first action-learning cycle of the VAPAR programme (2017–19). We collected data in three phases: (1) 10 individual interviews with programme stakeholders, including from government departments and parastatals, nongovernmental organizations and local communities; (2) an evaluative/exploratory workshop with provincial and district Department of Health managers; and (3) feedback and discussion of findings during an interactive workshop with national child health experts.

Results

Individual programme stakeholders described early outcomes relating to effective research and stakeholder engagement, and organization and delivery of services, with potential further contributions to the establishment of an evidence base for local policy and planning, and improved health outcomes. These outcomes were verified with provincial managers. Provincial and national stakeholders identified the potential for VAPAR to support engagement between communities and health authorities for collective planning and implementation of services. Provincial stakeholders proposed that this could be achieved through a two-way integration, with VAPAR stakeholders participating in routine health planning and review activities and frontline health officials being involved in the VAPAR process. Findings were collated into a revised theory of change.

Conclusions

The VAPAR learning platform was regarded as a feasible, acceptable and relevant approach to facilitate cooperative learning and community participation in health systems. The evaluation provides support for a collaborative learning platform within routine health system processes and contributes to the limited evaluative evidence base on embedded health systems research.
Pirfenidone attenuates synovial fibrosis and postpones the progression of osteoarthritis by anti-fibrotic and anti-inflammatory properties in vivo and in vitro
Authors: Wei Qilu , Kong Ning , Liu Xiaohui , Tian Run , Jiao Ming , Li Yiyang , Guan Huanshuai , Wang Kunzheng , Yang Pei
Published: April 2021

Background

Osteoarthritis (OA) is a disease of the entire joint involving synovial fibrosis and inflammation. Pathological changes to the synovium can accelerate the progression of OA. Pirfenidone (PFD) is a potent anti-fibrotic drug with additional anti-inflammatory properties. However, the influence of PFD on OA is unknown.

Methods

Proliferation of human fibroblast-like synoviocytes (FLSs) after treatment with TGF-β1 or PFD was evaluated using a Cell Counting Kit-8 assay and their migration using a Transwell assay. The expression of fibrosis-related genes (COL1A1, TIMP-1, and ACTA-2) and those related to inflammation (IL-6 and TNF-α) was quantified by real-time quantitative PCR. The protein expression levels of COL1A1, α-SMA (coded by ACTA-2), IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay. A rabbit model of OA was established and then PFD was administered by gavage. The expression of genes related to fibrosis (COL1A1, TIMP-1, and ADAM-12) and inflammation (IL-6 and TNF-α) was measured using RNA extracted from the synovium. Synovial tissue was examined histologically after staining with H&E, Masson’s trichrome, and immunofluorescence. Synovitis scores, the volume fraction of collagen, and mean fluorescence intensity were calculated. Degeneration of articular cartilage was analyzed using a Safranin O-fast green stain and OARSI grading.

Results

The proliferation of FLSs was greatest when induced with 2.5 ng/ml TGF-β1 although it did not promote their migration. Therefore, 2.5 ng/ml TGF-β1 was used to stimulate the FLSs and evaluate the effects of PFD, which inhibited the migration of FLSs at concentrations as low as 1.0 mg/ml. PFD decreased the expression of COL1A1 while TGF-β1 increased both mRNA and protein expression levels of IL-6 but had no effect on α-SMA or TNF-α expression. PFD decreased mRNA expression levels of COL1A1, IL-6, and TNF-α in vivo. H&E staining and synovitis scores indicated that PFD reduced synovial inflammation, while Masson’s trichrome and immunofluorescence staining suggested that PFD decreased synovial fibrosis. Safranin O-Fast Green staining and the OARSI scores demonstrated that PFD delayed the progression of OA.

Conclusions

PFD attenuated synovial fibrosis and inflammation, and postponed the progression of osteoarthritis in a modified Hulth model of OA in rabbits, which was related to its anti-fibrotic and anti-inflammatory properties.
4R-cembranoid confers neuroprotection against LPS-induced hippocampal inflammation in mice
Authors: Rojas-Colón Luis A. , Dash Pramod K. , Morales-Vías Fabiola A. , Lebrón-Dávila Madeline , Ferchmin Pedro A. , Redell John B. , Maldonado-Martínez Geronimo , Vélez-Torres Wanda I.
Published: April 2021

Background

Chronic brain inflammation has been implicated in the pathogenesis of various neurodegenerative diseases and disorders. For example, overexpression of pro-inflammatory cytokines has been associated with impairments in hippocampal-dependent memory. Lipopolysaccharide (LPS) injection is a widely used model to explore the pathobiology of inflammation. LPS injection into mice causes systemic inflammation, neuronal damage, and poor memory outcomes if the inflammation is not controlled. Activation of the alpha-7 nicotinic receptor (α7) plays an anti-inflammatory role in the brain through vagal efferent nerve signaling. 4R-cembranoid (4R) is a natural compound that crosses the blood-brain barrier, induces neuronal survival, and has been shown to modulate the activity of nicotinic receptors. The purpose of this study is to determine whether 4R reduces the deleterious effects of LPS-induced neuroinflammation and whether the α7 receptor plays a role in mediating these beneficial effects.

Methods

Ex vivo population spike recordings were performed in C57BL/6J wild-type (WT) and alpha-7-knockout (α7KO) mouse hippocampal slices in the presence of 4R and nicotinic receptor inhibitors. For in vivo studies, WT and α7KO mice were injected with LPS for 2 h, followed by 4R or vehicle for 22 h. Analyses of IL-1β, TNF-α, STAT3, CREB, Akt1, and the long-term novel object recognition test (NORT) were performed for both genotypes. In addition, RNA sequencing and RT-qPCR analyses were carried out for 12 mRNAs related to neuroinflammation and their modification by 4R.

Results

4R confers neuroprotection after NMDA-induced neurotoxicity in both WT and α7KO mice. Moreover, hippocampal TNF-α and IL-1β levels were decreased with 4R treatment following LPS exposure in both strains of mice. 4R restored LPS-induced cognitive decline in NORT. There was a significant increase in the phosphorylation of STAT3, CREB, and Akt1 with 4R treatment in the WT mouse hippocampus following LPS exposure. In α7KO mice, only pAkt levels were significantly elevated in the cortex. 4R significantly upregulated mRNA levels of ORM2, GDNF, and C3 following LPS exposure. These proteins are known to play a role in modulating microglial activation, neuronal survival, and memory.

Conclusion

Our results indicate that 4R decreases the levels of pro-inflammatory cytokines; improves memory function; activates STAT3, Akt1, and CREB phosphorylation; and upregulates the mRNA levels of ORM2, GDNF, and C3. These effects are independent of the α7 nicotinic receptor.
Influences of digital media use on children and adolescents with ADHD during COVID-19 pandemic
Authors: Shuai Lan , He Shan , Zheng Hong , Wang Zhouye , Qiu Meihui , Xia Weiping , Cao Xuan , Lu Lu , Zhang Jinsong
Published: April 2021

Objective

To explore the influences of digital media use on the core symptoms, emotional state, life events, learning motivation, executive function (EF) and family environment of children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) during the novel coronavirus disease 2019 (COVID-19) pandemic.

Method

A total of 192 participants aged 8–16 years who met the diagnostic criteria for ADHD were included in the study. Children scoring higher than predetermined cut-off point in self-rating questionnaires for problematic mobile phone use (SQPMPU) or Young’s internet addiction test (IAT), were defined as ADHD with problematic digital media use (PDMU), otherwise were defined as ADHD without PDMU. The differences between the two groups in ADHD symptoms, EF, anxiety and depression, stress from life events, learning motivation and family environment were compared respectively.

Results

When compared with ADHD group without PDMU, the group with PDMU showed significant worse symptoms of inattention, oppositional defiant, behavior and emotional problems by Swanson, Nolan, and Pelham Rating Scale (SNAP), more self-reported anxiety by screening child anxiety-related emotional disorders (SCARED) and depression by depression self-rating scale for children (DSRSC), more severe EF deficits by behavior rating scale of executive function (BRIEF), more stress from life events by adolescent self-rating life events checklist (ASLEC), lower learning motivation by students learning motivation scale (SLMS), and more impairment on cohesion by Chinese version of family environment scale (FES-CV). The ADHD with PDMU group spent significantly more time on both video game and social media with significantly less time spend on physical exercise as compared to the ADHD without PDMU group.

Conclusion

The ADHD children with PDMU suffered from more severe core symptoms, negative emotions, EF deficits, damage on family environment, pressure from life events, and a lower motivation to learn. Supervision of digital media usage, especially video game and social media, along with increased physical exercise, is essential to the management of core symptoms and associated problems encountered with ADHD.
Lack of the peroxiredoxin 6 gene causes impaired spatial memory and abnormal synaptic plasticity
Authors: Phasuk Sarayut , Jasmin Sureka , Pairojana Tanita , Chang Hsueh-Kai , Liang Kai-Chi , Liu Ingrid Y.
Published: April 2021

Peroxiredoxin 6 (PRDX6) is expressed dominantly in the astrocytes and exerts either neuroprotective or neurotoxic effects in the brain. Although PRDX6 can modulate several signaling cascades involving cognitive functions, its physiological role in spatial memory has not been investigated yet. This study aims to explore the function of the Prdx6 gene in spatial memory formation and synaptic plasticity. We first tested Prdx6−/− mice on a Morris water maze task and found that their memory performance was defective, along with reduced long-term potentiation (LTP) in CA3-CA1 hippocampal synapses recorded from hippocampal sections of home-caged mice. Surprisingly, after the probe test, these knockout mice exhibited elevated hippocampal LTP, higher phosphorylated ERK1/2 level, and decreased reactive astrocyte markers. We further reduced ERK1/2 phosphorylation by administering MEK inhibitor, U0126, into Prdx6−/− mice before the probe test, which reversed their spatial memory deficit. This study is the first one to report the role of PRDX6 in spatial memory and synaptic plasticity. Our results revealed that PRDX6 is necessary for maintaining spatial memory by modulating ERK1/2 phosphorylation and astrocyte activation.

Graphic Abstract
Intraperitoneal injection of lithium chloride induces lateralized activation of the insular cortex in adult mice
Authors: Qian Kai , Liu Jiaqi , Cao Yiqing , Yang Jing , Qiu Shuang
Published: April 2021

Insular cortex is a critical brain region that participates in the interoceptive sensations. Here, we combined the iDISCO + method and Fos immunostaining to confirm that the middle part of the right-side, but not the left-side, insular cortex in adult male mice is activated by intraperitoneal injection of lithium chloride. Lateralized activation of the insular cortex is also observed in adult female mice, but not in young or aged male mice. Furthermore, asymmetrical activation of the insular cortex was completely blocked when both sides of the vagal nerve are transected, whereas intravenous injection of lithium chloride has no effect on the insular activation. Combined together, these results indicate that the insular cortex unilaterally responds to aversive visceral stimuli in an age-dependent way and this process depends on the vagal afferent pathways.
Mobile App-based documentation of patient-reported outcomes — 3-months results from a proof-of-concept study on modern rheumatology patient management
Authors: Richter Jutta G. , Nannen Christina , Chehab Gamal , Acar Hasan , Becker Arnd , Willers Reinhart , Huscher Dörte , Schneider Matthias
Published: April 2021

Background

Mobile medical applications (Apps) offer innovative solutions for patients’ self-monitoring and new patient management opportunities. Prior to routine clinical application feasibility and acceptance of disease surveillance using an App that includes electronic (e) patient-reported outcome measures (PROMs) warrant evaluation. Therefore, we performed a proof-of-concept study in which rheumatoid arthritis (RA) patients used an App (RheumaLive) to document their disease.

Methods

Accurate PROM reporting via an App in comparison to paper-based versions was investigated to exclude media bias. Sixty participants recruited from 268 consecutive RA outpatients completed paper-based and electronic PROMs (Hannover Functional Questionnaire/derived HAQ; modified RA disease activity index) using the App at baseline and follow-up visits. Between visits, patients used their App on their own smartphone according to their preferences. The equivalence of PROM data and user experiences from patients and physicians were evaluated.

Results

Patients’ (78.3% female) mean (SD) age was 50.1 (13.1) years, disease duration 10.5 (9.1) years, and paper-based HAQ 0.78 (0.59). Mean confidence in Apps scored 3.5 (1.1, Likert scale 1 to 6). ePROMs’ scores obtained by patients’ data entry in the App were equivalent to paper-based ones and preferred by the patients. After 3 months, the App retention rate was 71.7%. Patients' overall satisfaction with the App was 2.2 (0.9, Likert scale 1 to 6). Patients and physicians valued the App, i.e., for patient-physician interaction: 87% reported that it was easier for them to document the course of the disease using the App than “only” answering questions about their current health during routine outpatient visits. Further App use was recommended in 77.3% of the patients, and according to physicians, in seven patients, the App use contributed to an increased adherence to therapy.

Conclusion

Our study provides an essential basis for the broader implementation of medical Apps in routine care. We demonstrated the feasibility and acceptance of disease surveillance using a smartphone App in RA. App use was convincing as a reliable option to perform continuous, remote monitoring of disease activity and treatment efficacy.

Trial registration

ClinicalTrials.gov, NCT02565225. Registered on September 16, 2015 (retrospectively registered).
Genetic variants of the EGFR ligand-binding domain and their association with structural alterations in Arab cancer patients
Authors: Marzouq Maryam , Nairouz Ali , Ben Khalaf Noureddine , Bourguiba-Hachemi Sonia , Quaddorah Raed , Ashoor Dana , Fathallah M. Dahmani
Published: April 2021

Objective

This study aimed to identify novel genetic variants in the CR2 extracellular domain of the epidermal growth factor receptor (EGFR) in healthy individuals and patients with six different types of adenocarcinoma, in Arabian peninsula populations. It also aimed to investigate the effects of these variants on the EGFR structure and their eventual relevance to tumorigenesis.

Results

We detected seven new EGFR genetic variants in 168 cancer patients and 114 controls. A SNP rs374670788 was more frequent in bladder cancer but not significantly associated to. However, a missense mutation (V550M) was significantly associated to colon, ovary, lung, bladder and thyroid cancer samples (p < 0.05). Three mutations (H590R, E602K and T605T) were found in the heterozygous form only in colon cancer patients. Genomic analysis of the synonymous mutation (G632G) showed that the T/A genotype could be associated to thyroid cancer in Arab patients (p < 0.05). An additional novel SNP rs571064657 was observed in control individuals. Computational analysis of the genetic variants revealed a reduction in the stabilization of the EGFR tethered form for both V550M and the common R521K variant with low energetic state (− ∆∆G). Molecular interactions analysis suggested that these mutations might affect the receptor’s function and promote tumorigenesis.