bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of CUB and sushi multiple domains 1 (CSMD1) expression by miRNA-190a-3p enhances hypertrophic scar-derived fibroblast migration in vitro
Authors: Gu Shuchen , Huang Xin , Xu Xiangwen , Liu Yunhan , Khoong Yimin , Zhang Zewei , Li Haizhou , Gao Yashan , Zan Tao
Published: August 2021

Background

Hypertrophic scar (HTS) is a fibroproliferative skin disorder characterized by excessive cell proliferation, migration, and extracellular matrix (ECM) deposition. The CUB and Sushi multiple domains 1 (CSMD1) has previously been identified as the key regulatory gene of hypertrophic scar by a large sample GWAS study. However, further research has not yet been conducted to verify this finding in other HTS patients and to determine the underlying mechanism.

Results

In this study, we verified that CSMD1 was downregulated in both HTS tissue and HTS-derived fibroblasts. The knockdown of CSMD1 resulted in enhanced migration and fibronectin1 (FN1) secretion in fibroblasts in vitro. In addition, the upstream and downstream regulatory mechanisms of CSMD1 were also investigated through microRNA (miRNA) databases screening and RNA-sequencing (RNA-seq) respectively. The screening of four common microRNA (miRNA) databases suggested that miR-190a-3p binds to the CSMD1 and may regulate its expression. We confirmed that miR-190a-3p directly targeted the CSMD1–3′-UTR using luciferase reporter assays. Furthermore, the overexpression of miR-190a-3p showed promotion of migratory activity and FN1 secretion in fibroblasts, resembling the effect of CSMD1 knockdown; whereas the knockdown of miR-190a-3p exerted the opposite effect. Finally, transcriptomic analysis showed activation of Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway in the CSMD1 knockdown fibroblasts.

Conclusions

This study has validated the conclusions of the previous GWAS study conducted in Chinese population. In vitro experiments have provided further evidence on the function of CSMD1 in the development of HTS, and have also revealed the underlying upstream and downstream regulating mechanisms. Additionally, the JAK/STAT signaling pathway identified using RNA-seq might provide a potential treatment approach, especially for HTS.
Ameliorative effect of melatonin improves drought tolerance by regulating growth, photosynthetic traits and leaf ultrastructure of maize seedlings
Authors: Ahmad Shakeel , Muhammad Ihsan , Wang Guo Yun , Zeeshan Muhammad , Yang Li , Ali Izhar , Zhou Xun Bo
Published: August 2021

Background

Melatonin is considered a potential plant growth regulator to enhance the growth of plants and increase tolerance to various abiotic stresses. Nevertheless, melatonin’s role in mediating stress response in different plant species and growth cycles still needs to be explored. This study was conducted to understand the impact of different melatonin concentrations (0, 50, 100, and 150 μM) applied as a soil drench to maize seedling under drought stress conditions. A decreased irrigation approach based on watering was exposed to maize seedling after drought stress was applied at 40–45% of field capacity.

Results

The results showed that drought stress negatively affected the growth behavior of maize seedlings, such as reduced biomass accumulation, decreased photosynthetic pigments, and enhanced the malondialdehyde and reactive oxygen species (ROS). However, melatonin application enhanced plant growth; alleviated ROS-induced oxidative damages by increasing the photosynthetic pigments, antioxidant enzyme activities, relative water content, and osmo-protectants of maize seedlings.

Conclusions

Melatonin treatment also enhanced the stomatal traits, such as stomatal length, width, area, and the number of pores under drought stress conditions. Our data suggested that 100 μM melatonin application as soil drenching could provide a valuable foundation for improving plant tolerance to drought stress conditions.
Clinical features and risk factors of postoperative in-hospital mortality following surgical repair of Stanford type A acute aortic dissection
Authors: Ke Chen , Wu Hao , Xi Min , Shi Wei , Huang Qihong , Lu Guirong
Published: August 2021

Background

To investigate the clinical features of patients with Stanford type A acute aortic dissection (AAD) and analyze the risk factors affecting postoperative in-hospital mortality rate.

Methods

The demographic and clinical data were retrospectively collected and analyzed from 118 AAD patients admitted to the Affiliated Hospital of Hangzhou Normal University from June 2016 to April 2019. All patients underwent surgical treatment and were grouped into death and survival groups. The risk factors affecting postoperative in-hospital death were analyzed using multivariate logistic regression analysis.

Results

The male to female ratio in the patients was 3.8:1 and the mean age was 50.11 ± 9.91 years. The patient’s main comorbidities were hypertension (70.33%) and coronary heart disease (10.17%). The main symptoms included chest pain and back pain (72.89%). The highest incidence of complications was pericardial effusion (48.31%), followed by pleural effusion (22.88%). The mean systolic blood pressure, white blood cell count and D-dimer in the patients were over the ranges of normal people. The incidences of cardiac and renal insufficiency were 18.64% and 16.95% respectively, and the postoperative in-hospital mortality rate was 12.71%. Univariable analysis showed that age, renal insufficiency, cardiac insufficiency, D-dimer level, cardiopulmonary bypass time, operation time, blood transfusion volume and postoperative hemostasis were significant factors leading to the death (P < 0.05). Multivariate logistic regression analysis showed that age > 65, renal insufficiency, cardiopulmonary bypass time ≥ 250 min and postoperative hemostasis were independent risk factors for the death (P < 0.05).

Conclusions

AAD patients frequently have underlying diseases with pain as the main symptom. Age > 65 years, renal insufficiency, cardiopulmonary bypass time ≥ 250 min and postoperative hemostasis are significantly risk factors for postoperative mortality.
Potential of high dimensional radiomic features to assess blood components in intraaortic vessels in non-contrast CT scans
Authors: Mahmoudi Scherwin , Martin Simon S. , Ackermann Jörg , Zhdanovich Yauheniya , Koch Ina , Vogl Thomas J. , Albrecht Moritz H. , Lenga Lukas , Bernatz Simon
Published: August 2021

Background

To assess the potential of radiomic features to quantify components of blood in intraaortic vessels to non-invasively predict moderate-to-severe anemia in non-contrast enhanced CT scans.

Methods

One hundred patients (median age, 69 years; range, 19–94 years) who received CT scans of the thoracolumbar spine and blood-testing for hemoglobin and hematocrit levels ± 24 h between 08/2018 and 11/2019 were retrospectively included. Intraaortic blood was segmented using a spherical volume of interest of 1 cm diameter with consecutive radiomic analysis applying PyRadiomics software. Feature selection was performed applying analysis of correlation and collinearity. The final feature set was obtained to differentiate moderate-to-severe anemia. Random forest machine learning was applied and predictive performance was assessed. A decision-tree was obtained to propose a cut-off value of CT Hounsfield units (HU).

Results

High correlation with hemoglobin and hematocrit levels was shown for first-order radiomic features (p < 0.001 to p = 0.032). The top 3 features showed high correlation to hemoglobin values (p) and minimal collinearity (r) to the top ranked feature Median (p < 0.001), Energy (p = 0.002, r = 0.387), Minimum (p = 0.032, r = 0.437). Median (p < 0.001) and Minimum (p = 0.003) differed in moderate-to-severe anemia compared to non-anemic state. Median yielded superiority to the combination of Median and Minimum (p(AUC) = 0.015, p(precision) = 0.017, p(accuracy) = 0.612) in the predictive performance employing random forest analysis. A Median HU value ≤ 36.5 indicated moderate-to-severe anemia (accuracy = 0.90, precision = 0.80).

Conclusions

First-order radiomic features correlate with hemoglobin levels and may be feasible for the prediction of moderate-to-severe anemia. High dimensional radiomic features did not aid augmenting the data in our exemplary use case of intraluminal blood component assessment.

Trial registration Retrospectively registered.
Interaction between DNMT3B and MYH11 via hypermethylation regulates gastric cancer progression
Authors: Wang Jianhua , Xu Ping , Hao Yanping , Yu Tingting , Liu Limin , Song Yan , Li Yan
Published: August 2021

Background

Gastric cancer (GC) has an unwelcoming prognosis when diagnosed at an advanced stage. The purpose of this study was to examine the expression of myosin heavy chain 11 (MYH11) in GC and mechanisms related.

Methods

The MYH11 expression in GC was investigated via the SangerBox platform. MYH11 expression in GC tissues and cell lines was examined by immunohistochemistry, RT-qPCR, and western blot. The relationship between MYH11 expression and patients’ prognosis was analyzed. The effects of MYH11 on the biological behaviors of GC cells were investigated by gain-of-function experiments. Bioinformatics analysis was used to find genes with relevance to MYH11 expression in GC. The relationship was verified by luciferase and ChIP-qPCR assays, followed by rescue assay validation. The causes of MYH11 downregulation in GC were verified by quantitative methylation-specific PCR. Finally, the effect of MYH11 on tumor growth was examined.

Results

MYH11 was downregulated in GC and predicted poor prognoses. MYH11 reverted the malignant phenotype of GC cells. MYH11 repressed the TNFRSF14 expression by binding to the TNFRSF14 promoter. TNFRSF14 reversed the inhibitory effect of MYH11 on the malignant phenotype of GC cells. The methylation of the MYH11 promoter was elevated in GC, which was correlated with the elevated DNMT3B in GC. Overexpression of DNMT3B repressed transcription of MYH11 by promoting its methylation. Also, MYH11 upregulation inhibited tumor growth.

Conclusion

DNMT3B inhibits MYH11 expression by promoting its DNA methylation, thereby attenuating the repressive effect of MYH11 on the transcriptional of TNFRSF14 and promoting the progression of GC.
Effect of using knee valgus brace on pain and activity level over different time intervals among patients with medial knee OA: systematic review
Authors: Alfatafta Huda , Onchonga David , Alfatafta Mahmoud , Zhang lu , Boncz Imre , Lohner Szimonetta , Molics Bálint
Published: August 2021

Background

The Knee valgus brace is one of the accepted conservative interventions for patients with medial compartment knee osteoarthritis to correct the knee varus and increase functional activity level. Nevertheless, comprehensive overview of the effects of using this brace on self-reported pain activity level over time is not available. Thus, this study aimed to systematically review the effect of using this brace on pain and activity levels in the last 20 years in patients with medial compartment knee osteoarthritis.

Methods

Five databases were searched to find articles from the year 2000 to the end of November 2020: Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, PubMed, Web of Science, and Scopus. Two reviewers independently evaluated the available articles for eligibility and assessed quality. The risk of bias in each study was assessed by two reviewers independently according to the Strengthening the Reporting of Observational Studies in Epidemiology tool (STROBE) for the non-randomized controlled studies and the Cochrane risk-of-bias tool for the randomized controlled studies.

Results

Seven randomized controlled studies and 17 cohort studies (in total 579 participants) were included in the systematic review. Most of these studies found using a knee valgus brace effective in reducing pain and improving activity level over different time intervals. The majority of the included studies (14 studies) evaluated the impact of the brace for a considerably short-term (less than 6 months). Thus, limited evidence is available on the long-term use of the knee valgus brace and its associated complications.

Conclusion

The knee valgus brace is an effective conservative intervention to improve the quality of life and reduce pain during daily activities for some patients. However, the long term of using this brace is still not very convenient, and the patients who benefit most from using the brace should be identified with high methodological quality studies.
Finite element analysis of the kinematic coupling effect of the joints around talus when Ponseti manipulation
Authors: Li Song-Jian , Shi Ben-Chao , Liu Cheng-Long , Liu Yu-Bin
Published: August 2021

Background

Little information was obtained from the published papers about the kinematic coupling effect between tarsal bones during Ponseti manipulation. The aim was to explore the kinematic coupling effect of the joints around talus, to investigate the kinematic rhythm and coupling relationship of tarsal joints; to clarify the pulling effect on medial ligament of the ankle during the process of Ponseti manipulation.

Methods

The model of foot and ankle was reconstructed from the Chinese digital human girl No.1 (CDH-G1) image database. Finite element analysis was applied to explore the kinematic coupling effect of the joints around talus. The distal tibia and fibula bone and the head of talus were fixed in all six degrees of freedom; outward pressure was added to the first metatarsal head to simulate the Ponseti manipulation. Kinematic coupling of each tarsal joint was investigated using the method of whole model splitting, and medial ligament pulling of the ankle was studied by designing the model of medial ligament deletion during the Ponseti manipulation.

Results

All the tarsal joints produced significant displacement in kinematic coupling effect, and the talus itself produced great displacement in the joint of ankle. Quantitative analysis revealed that the maximum displacement was found in the joints of talonavicular (12.01mm), cuneonavicular (10.50mm), calcaneocuboid (7.97mm), and subtalar(6.99mm).The kinematic coupling rhythm between talus and navicular, talus and calcaneus, calcaneus and cuboid, navicular and cuneiform 1 were 1:12, 1:7, 1:2 and 1:1.6. The results of ligaments pulling showed that the maximum displacement was presented in the ligaments of tibionavicular (mean 27.99mm), talonavicular (21.03mm), and calcaneonavicular (19.18 mm).

Conclusions

All the tarsal joints around talus were involved in the process of Ponseti manipulation, and the strongest kinematic coupling effect was found in the joints of talonavicular, subtalar, calcaneocuboid, and cuneonavicular. The ligaments of tibionavicular, talonavicular, and calcaneonavicular were stretched greatly. It was suggested that the method of Ponseti management was a complex deformity correction processes involved all the tarsal joints. The present study contributed to better understanding the principle of Ponseti manipulation and the pathoanatomy of clubfoot. Also, the importance of cuneonavicular joint should be stressed in clinical practice.
Effectiveness and cost-effectiveness of primary arthrodesis versus open reduction and internal fixation in patients with Lisfranc fracture instability (The BFF Study) study protocol for a multicenter randomized controlled trial
Authors: van den Boom N. A. C. , Stollenwerck G. A. N. L. , Evers S. M. A. A. , Poeze M.
Published: August 2021

Background

The Lisfranc injury is a complex injury of the midfoot. It can result in persistent pain and functional impairment if treated inappropriately. In Lisfranc fracture dislocation, treatment options are primary arthrodesis of the midfoot joints or open reduction and internal fixation. The purpose of the proposed study is to define the optimal treatment for the Lisfranc fracture dislocation, either primary arthrodesis or open reduction and internal fixation, in regard to quality of life, complications, functional outcomes, and cost effectiveness.

Methods

Study design: A prospective multicenter RCT. Study population: All patients of 18 years and older with an acute (< 6 weeks) traumatic fracture dislocation in the Lisfranc midfoot joints, displaced on static radiographic evaluation or unstable with dynamic evaluation, weight bearing radiographs or fluoroscopic stress testing under anesthesia, and eligible for either one of the surgical procedures. In total, this study will include n = 112 patients with Lisfranc fracture dislocation. Interventions: Patients with Lisfranc fracture dislocation will be randomly allocated to treatment in “The Better to Fix or Fuse Study” (The BFF Study) with either PA or ORIF. Main study parameters/endpoints: Primary outcome parameter: the quality of life. Secondary outcomes: complications, functional outcomes, secondary surgical interventions and cost effectiveness. Nature and extent of the burden: PA is expected to have a better outcome, however both treatments are accepted for this injury with a similar low risk of complications. Follow up is standardized and therefore this study will not add extra burden to the patient.

Discussion

This study protocol provides a comprehensive overview of the aims and methods of the attached clinical study. Limitations of this study are the absence of patient blinding since it is impossible in surgical intervention, and the outcome measure (AOFAS) that has limited validity not for these injuries. This study will be the first with enough power to define optimal treatment for Lisfranc fracture dislocations. This is necessary since current literature is unclear on this topic.

Trial registration Current controlled Trial: NCT04519242 with registration date: 08/13/2020. Retrospectively registered; Protocol date and version: Version 4 05/06/2020
Three-dimensional reduction method with a modified C2 isthmus screw in irreducible atlantoaxial dislocation: a technical note
Authors: Zhou Shengyuan , Yuan Bo , Liu Weicong , Tang Yifan , Chen Xiongsheng , Jia Lianshun
Published: August 2021

Background

Three-dimensional reduction plays a vital role in surgical reduction of irreversible atlantoaxial dislocation (IAAD). However, the most commonly used combination of C1 pedicle screw (PS) or lateral mass screw (LMS) and C2 PS or isthmus screw often fails to achieve satisfactory reduction at one time. The difficulty is usually caused by short anteroposterior and vertical distance between heads of C1 and C2 screws, which lack enough space for reduction operation. The objective of this study is to describe a three-dimensional reduction method with a modified C2 isthmus screw and to illustrate its advantage and effectiveness for IAAD.

Methods

Twelve patients with IAAD underwent reduction and fixation with modified C2 isthmus screw combined with C1 PS or LMS, fusion with autologous bone graft. The insertion point was lateral to the intersection of caudal edge of C2 lamina and lateral mass, with a trajectory towards C2 isthmus, via lateral mass. The three-dimensional reduction was achieved through pulling and distracting. Radiographic evaluation included anteroposterior and direct distance between different insertion points, the occipitoaxial angle (O-C2A), clivus-canal angle (CCA) and cervicomedullary angle (CMA). Clinical outcomes evaluation included the Japanese Orthopaedic Association (JOA) score, Visual analog scale (VAS) and Neck Disability Index (NDI).

Results

All the patients maintained effective reduction during the follow-up. The anteroposterior and direct distance was significantly higher in modified C2 isthmus screw than C2 PS whether combined with C1 PS or LMS (P < 0.05). The degree of O-C2A, CCA and CMA, JOA score, NDI, and VAS were significantly improved after the surgery (P < 0.05).

Conclusions

Three-dimensional reduction method with a modified C2 isthmus screw is effective and safe in managing IAAD. It can increase the anteroposterior and vertical distance between the heads of C1 and C2 screws, which is benefit for the three-dimensional reduction operation of IAAD.
Concurrence of overt Cushing’s syndrome and primary aldosteronism accompanied by aldosterone-producing cell cluster in adjacent adrenal cortex: case report
Authors: Fushimi Yoshiro , Tatsumi Fuminori , Sanada Junpei , Shimoda Masashi , Kamei Shinji , Nakanishi Shuhei , Kaku Kohei , Mune Tomoatsu , Kaneto Hideaki
Published: August 2021

Background

Various adrenal disorders including primary aldosteronism and Cushing’s syndrome lead to the cause of hypertension. Although primary aldosteronism is sometimes complicated with preclinical Cushing’s syndrome, concurrence of overt Cushing’s syndrome and primary aldosteronism is very rare. In addition, it has been drawing attention recently that primary aldosteronism is brought about by the presence of aldosterone-producing cell cluster in adjacent adrenal cortex rather than the presence of aldosterone-producing adenoma.

Case presentation

A 67-year-old Japanese female was referred to our institution due to moon face and central obesity. Based on various clinical findings and data, we diagnosed this subject as overt Cushing’s syndrome and primary aldosteronism. Furthermore, in immunostaining for cytochrome P450 (CYP) 11B1, a cortisol-producing enzyme, diffuse staining was observed in tumorous lesion. Also, in immunostaining for CYP11B2, an aldosterone-producing enzyme, CYP11B2 expression was not observed in tumorous lesion, but strong CYP11B2 expression was observed in adjacent adrenal cortex, indicating the presence of aldosterone-producing cell cluster.

Conclusions

We should bear in mind the possibility that concurrence of overt Cushing’s syndrome and primary aldosteronism is accompanied by aldosterone-producing cell cluster in adjacent adrenal cortex.
Association between vitamin D and glycaemic parameters in a multi-ethnic cohort of postmenopausal women with type 2 diabetes in Saudi Arabia
Authors: Alharazy Shatha , Alissa Eman , Lanham-New Susan , Naseer Muhammad Imran , Chaudhary Adeel G. , Robertson M Denise
Published: August 2021

Background

The relationship between vitamin D (VitD) and insulin sensitivity and secretion in type 2 diabetes mellitus (T2D) has been shown to be different amongst different ethnic populations. In Saudi Arabia, where both T2D and VitD deficiency are highly prevalent health concerns, little is known about the relationship between VitD, insulin sensitivity, resistance and the relative importance of ethnicity. Our primary aim in this study was to investigate influence of ethnicity on VitD association with glycaemic profile and to measures of obesity as a secondary outcome, among multiethnic postmenopausal women with T2D in Saudi Arabia.

Methods

A cross-sectional study was conducted at King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. Postmenopausal females (n = 173, age ≥ 50 years) with T2D were randomly selected in this study. Anthropometric measures and fasting blood samples were obtained for all study participants. Several biochemical parameters were measured including 25-hydroxyvitamin D (25(OH)D), glycosylated hemoglobin (HbA1c), insulin, glucose and c-peptide. Surrogate markers for insulin resistance were calculated using Homeostasis Model Assessment 2 for insulin resistance and beta cell activity (HOMA2-IR, HOMA2-β).

Results

Overall, 25(OH)D was inversely associated with fasting glucose (r=-0.165,P = 0.037), insulin (r=-0.184,P = 0.02), C-peptide (r=-0.19,P = 0.015) and HOMA2- IR C-peptide (r=-0.23, P = 0.004). Additionally, serum 25 (OH)D showed a negative correlation with body weight (r=-0.173P = 0.028), waist and hip circumferences (r=-0.167,P = 0.033;r=-0.22,P = 0.004 respectively) but not with body mass index (BMI) or waist hip ratio (WHR).

In the white ethnic group but not in black or Asian population groups, 25(OH)D level was also associated with only serum fasting C-peptide and HOMA2-IR C-peptide and BMI (P < 0.05).

Conclusions

Insulin resistance and obesity were associated with VitD status in T2D in this cohort. Our findings also suggest that these VitD associations in women from white ethnic background are different than in those from black/Asian ethnic backgrounds. Whether VitD supplements are able to improve either obesity and/or insulin sensitivity should be further investigated in different ethnic population groups.
Peer review in team-based learning: influencing feedback literacy
Authors: Burgess Annette , Roberts Chris , Lane Andrew Stuart , Haq Inam , Clark Tyler , Kalman Eszter , Pappalardo Nicole , Bleasel Jane
Published: August 2021

Background

Peer review in Team-based learning (TBL) exists for three key reasons: to promote reflection on individual behaviours; provide opportunities to develop professional skills; and prevent ‘free riders’ who fail to contribute effectively to team discussions. A well-developed process that engages students is needed. However, evidence suggests it remains a difficult task to effectively incorporate into TBL. The purpose of this study was to assess medical students’ ability to provide written feedback to their peers in TBL, and to explore students’ perception of the process, using the conceptual framework of Biggs ‘3P model’.

Methods

Year 2 students (n = 255) participated in peer review twice during 2019. We evaluated the quality of feedback using a theoretically derived rubric, and undertook a qualitative analysis of focus group data to seek explanations for feedback behaviors.

Results

Students demonstrated reasonable ability to provide positive feedback, but were less prepared to identify areas for improvement. Their ability did not improve over time, and was influenced by the perceived task difficulty; social discomfort; and sense of responsibility in providing written feedback.

Conclusions

To increase student engagement, we require a transparent process that incorporates verbal feedback and team discussion, with monitoring of outcomes by faculty and adequate training.
Designing a system for performance appraisal: balancing physicians’ accountability and professional development
Authors: Bindels Elisa , Boerebach Benjamin , Scheepers Renée , Nooteboom Annemiek , Scherpbier Albert , Heeneman Sylvia , Lombarts Kiki
Published: August 2021

Background

In many healthcare systems, physicians are accustomed to periodically participate in individual performance appraisals to guide their professional development. For the purpose of revalidation, or maintenance of certification, they need to demonstrate that they have engaged with the outcomes of these appraisals. The combination of taking ownership in professional development and meeting accountability requirements may cause undesirable interference of purposes. To support physicians in their professional development, new Dutch legislation requires that they discuss their performance data with a non-hierarchical (peer)coach and draft a personal development plan. In this study, we report on the design of this system for performance appraisal in a Dutch academic medical center.

Methods

Using a design-based research approach, a hospital-based research group had the lead in drafting and implementing a performance appraisal protocol, selecting a multisource feedback tool, co-developing and piloting a coaching approach, implementing a planning tool, recruiting peer coaches and facilitating their training and peer group debriefings.

Results

The system consisted of a two-hour peer-to-peer conversation based on the principles of appreciative inquiry and solution-focused coaching. Sessions were rated as highly motivating, development-oriented, concrete and valuable. Peer coaches were considered suitable, although occasionally physicians preferred a professional coach because of their expertise. The system honored both accountability and professional development purposes. By integrating the performance appraisal system with an already existing internal performance system, physicians were enabled to openly and safely discuss their professional development with a peer, while also being supported by their superior in their self-defined developmental goals. Although the peer-to-peer conversation was mandatory and participation in the process was documented, it was up to the physician whether or not to share its results with others, including their superior.

Conclusions

In the context of mandatory revalidation, professional development can be supported when the appraisal process involves three characteristics: the appraisal process is appreciative and explores developmental opportunities; coaches are trustworthy and skilled; and the physician has control over the disclosure of the appraisal output. Although the peer-to-peer conversations were positively evaluated, the effects on physicians’ professional development have yet to be investigated in longitudinal research designs.
Cultural determinants of health for Aboriginal and Torres Strait Islander people – a narrative overview of reviews
Authors: Verbunt Ebony , Luke Joanne , Paradies Yin , Bamblett Muriel , Salamone Connie , Jones Amanda , Kelaher Margaret
Published: August 2021

Introduction

The cultural determinants of health centre an Indigenous definition of health, and have been linked to positive health and wellbeing outcomes. There is growing evidence for the importance of the cultural determinants of health; however, to date, no high-level overview of the evidence-base has been provided. Synthesising existing literature on cultural determinants of health for Aboriginal peoples in a single manuscript will highlight what we know, and what needs to be explored in future research. It will also contribute to global efforts to capture the evidence of cultural determinant approaches amongst Indigenous populations. We therefore endeavoured to identify cultural determinants and highlight their impact on Aboriginal health and wellbeing outcomes, and outline the relationship and interconnection of different cultural determinants of health.

Methods

An overview of reviews was conducted. Medline (Ovid) and Scopus were searched using terms related to ‘cultural determinants of health’ and an ‘Aboriginal definition of health’. The database search was complemented by a web-based search of grey literature. Nine reviews were retrieved and included in our overview.

Results

Family/community, Country and place, cultural identity and self-determination were strongly identified across reviews as having a positive impact on the health and wellbeing outcomes of Aboriginal peoples. Family/community and Country and place were found to be components of ‘culture’ that shaped cultural identity. Self-determination was outlined as a requirement for Aboriginal peoples to pursue their cultural, social, and economic rights.

Discussion/conclusions

Cultural determinants are associated with health benefits for Indigenous peoples. A causal framework, developed to discuss the relationship and interconnection of the cultural determinants of health, demonstrates that cultural identity at an individual-level is important to benefiting from other cultural determinants of health. While self-determination and connection to culture and community-controlled organisations are integral factors to increase Aboriginal resilience and resistance and improve health and wellbeing outcomes. Further research is required to shift towards a multi-level understanding of the cultural determinants of health and to develop an Indigenous-led evidence-base around causal pathways. Such a shift would ensure priorities important to Indigenous peoples are captured in policy and practice.
Apoptotic investigation of brain tissue cells in dogs naturally infected by canine distemper virus
Authors: Pan Yaoqian , Wang Shuai , Li Peng , Yue Feng , Zhang Yanfang , Pan Bo , Liu Xingyou
Published: August 2021

Background

Canine distemper caused by canine distemper virus that belongs to the Morbillivirus genus of the Paramyxoviridae family is still a global epidemic significant infectious disease, especially in pet dogs in China and serious harm to the development of the dog industry. It has been known that apoptosis caused by the canine distemper virus can show in culture cells, lymphoid tissues, and the cerebellum. However, its occurrence in brain tissue cells remains unclear. To investigate the relationship among canine distemper infecting brain tissues, apoptosis in brain tissue cells, and demyelinating pathogenesis was investigated.

Methods

16 naturally infected dogs that exhibited clinical signs of CD and tested positive for the anti-CDV monoclonal antibody and six healthy dogs that served as the control, were used in the research. Brain specimens were divided into the cerebrum, brain stem, and cerebellum embedded in paraffin and made the sections respectively. Approximately 5 µm-thick sections were stained by hematoxylin–eosin, methyl green pyronin, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique, and immunohistochemistry. CDV nucleocapsid protein was detected by immune streptavidin-biotinylated peroxidase complex.

Results

Alterations in the brain tissues of CDV-infected dogs involved both various cells and nerve fibers. CDV had varying degrees of cytotropism to all brain tissue cells; apoptosis also occurred in all brain cells, especially in the endothelia of cerebral vessels, astrocytes, oligodendrocytes, and ependymal cells, the more serious infection, the more obvious apoptosis. Serious infections also involved the pyramidal and Purkinje cells. The nervous fibers exhibited demyelinating lesions (showed small multifocal vacuole), and some axonal neuron atrophy gradually disappeared (formed large vacuole).

Conclusions

Apoptosis in brain tissue cells was mainly related to the propagation path and cytotropism of CDV. The apoptosis of astrocytes, oligodendrocytes, and some neurons may play a significant role in the demyelinating pathogenesis in dogs with acute canine distemper. A lot of diverse nervous signs shown in the clinic may be related to different neuron apoptosis.
Stereotactic ablative body radiotherapy boost for cervical cancer when brachytherapy boost is not feasible
Authors: Lee Tae Hoon , Song Changhoon , Kim In Ah , Kim Jae-Sung , Kim Yong Beom , Kim Kidong , No Jae Hong , Suh Dong Hoon , Chung Jin-Beom , Eom Keun-Yong
Published: August 2021

Background

The purpose of this study was to analyze the treatment efficacy and safety of stereotactic ablative body radiotherapy (SABR) boost for cervical cancer patients not amenable to brachytherapy.

Methods

A retrospective review of the medical records from single institution of 25 eligible patients was performed. The patients underwent pelvic radiotherapy (RT) in 25 or 28 fractions with a median dose of 45 Gy (range 44–50.4 Gy). SABR boost was delivered after pelvic RT, with a median dose of 25 Gy (range 20–33 Gy), and a median fraction number of 5 (range 4–6). 21 patients with a follow-up period of more than one year were included in the toxicity analysis, and hematuria and hematochezia that occurred later than 3 months after the RT were graded.

Results

The median follow-up period after radiotherapy was 2.85 years (range 0.33–6.60). The 3-year local control, locoregional control, disease-free survival, and overall survival rates were 80.9%, 75.8%, 40.9%, and 77.1%, respectively. 5 patients experienced grade 3 toxicity (3 genitourinary, 3 gastrointestinal), and no grade 4–5 toxicity was reported. Univariate analysis showed that cumulative D2cc in equivalent dose in 2 Gy fractions (EQD2) of rectum was marginally predictive for any grade of hematochezia (P = 0.051). Cumulative D2cc EQD2 of bladder was not predictive for hematuria. In the receiver operating characteristic (ROC) curve analysis, the optimal threshold of cumulative rectal D2cc EQD2 was 81.2 Gy for any grade of hematochezia.

Conclusion

SABR boost for cervical cancer was effective and tolerable. Although it cannot substitute brachytherapy, it can be a treatment option when brachytherapy is not possible.
Application of unilateral external fixation by the “joystick technique” in the treatment of pediatric tibia shaft fractures: technical note
Authors: Wang Xinhui , Zhang Zhe , Hou Xizhi , Wang Bao , Li Yongdong , Zhang Tao
Published: August 2021

Background

The aims of current study were to present the clinical outcomes in patients with pediatric tibia shaft fractures who were treated with unilateral external fixation combined with joystick for fracture reduction and describe the details of our technique.

Methods

We retrospectively analyzed the patients with pediatric tibia shaft fractures who were treated with unilateral external fixation combined with joystick for fracture reduction between July 2018 and March 2020. The clinical outcomes were evaluated.

Results

A total of 23 patients were included in the current study with the average age of 8.0 years (ranged 4–14 years). The average duration of hospital and follow-up were 5.9 days (ranged 4–8 days) and 17.4 months (ranged 8–27 months), respectively. At postoperative 3 days, the visual analog scale (VAS) score was 3.1 ± 1.43, which was significantly lower than the preoperative score of 7.3 ± 1.5. Of these, 2 cases showed redness and swelling of pin-tract and exudation at postoperative 1 month, who improved after oral antibiotics without causing fixation failure. The average time to full weight-bearing without crutches was 5.1 weeks (ranged 3–8 weeks). All patients achieved fracture healing and good functional recovery. No complications including fixation failure, reoperation, epiphyseal injury occurred, infection around implants, vessel damage, nerve damage, and limitation of joint movement were observed. The Johner-Wruh scores showed that 21 cases (91.3%) were “excellent” and 2 cases (8.7%) were “good.”

Conclusions

This procedure had advantages of simple operation, minimum trauma, early recovery of lower limb function, and no risk of complications. It may provide a new choice for children with tibia shaft fractures who require surgical treatment.
Fast-track versus conventional surgery in relation to time of hospital discharge following total hip arthroplasty: a single-center prospective study
Authors: de Carvalho Almeida Raul Frankllim , Serra Humberto Oliveira , de Oliveira Liszt Palmeira
Published: August 2021

Background

Total hip arthroplasty (THA) has been used for over five decades for treating hip osteoarthritis. THA is a surgical procedure associated with prolonged hospital length of stay (LOS). The aim of this study was to analyze whether a protocol developed for fast-track THA could decrease the time taken to reach functional recovery after surgery and the hospital LOS. Blood transfusion and critical care requirements and the complication rate were evaluated as secondary endpoints.

Methods

Ninety-eight patients underwent THA at the University Hospital of the Federal University of Maranhão (São Luís, Brazil). The control group included 51 patients who underwent THA through the conventional method. The fast-track surgery (FTS) group included 47 patients who underwent THA through the FTS approach. The inclusion criteria were that the subjects needed to present hip osteoarthritis and at least one clinical indication for THA, and that their risk classification was in ASA category I or II. The following factors were evaluated: age, sex, diagnosis, laterality, type of arthroplasty, blood transfusion, critical care requirement, complications, LOS, and need for re-hospitalization for any reason. For spinal anesthesia, an opioid-free protocol was used. Comparison of categorical variables between the groups was performed using the chi-square test, Shapiro-Wilk test, Studentttest, and Poisson regression approach.

Results

The FTS and control groups were similar in age and sex distribution (p> 0.05). The majority of the patients in the control group required both blood transfusion and use of the critical care unit, thus differing from the patients who underwent FTS (p< 0.001). The mean hospital LOS in the FTS group was 2.3 ± 0.8 days, compared with 6.4 ± 1.5 days in the control group (p < 0.001).

Conclusion

Use of FTS was associated with decreased LOS, compared with conventional THA.

Trial registration

https://www.researchsquare.com/article/rs-369025/v1.
Soluble urokinase plasminogen activator receptor and lactate as prognostic biomarkers in patients presenting with non-specific chief complaints in the pre-hospital setting – the PRIUS-study
Authors: Ivic Robert , Nurmi Jouni , Kurland Lisa , Vicente Veronica , Lindström Veronica , Djärv Therese , Kaartinen Johanna , Castrén Maaret , Bohm Katarina
Published: August 2021

Background

Emergency Medical Services (EMS) are faced daily with patients presenting with non-specific chief complaints (NSC). Patients presenting with NSCs often have normal vital signs. It has previously been established that NSCs may have a serious underlying condition that has yet to be identified. The aim of the current study was to determine if soluble urokinase plasminogen activator receptor (suPAR) and lactate could be used to identify serious conditions among patients presenting with NSCs to the EMS. The secondary aim was to describe the prognostic value for mortality in the group.

Method

A blinded prospective observational cohort study was conducted of patients brought to the ED by ambulance after calling the national emergency number 112 and who were assessed as having NSC by the EMS. Biomarkers were measured during index EMS assessment before transportation to the ED. Patients were followed via EMS and hospital electronic health records. Descriptive and logistic regression analyses were used.

Results

A total of 414 patients were included, with a median age of 82 years. A serious condition was present in 15.2% of the patients. Elevated suPAR above 3 ng/ml had a positive likelihood ratio (LR+) of 1.17 and a positive predictive value (PPV) of 17.3% as being predictive of a prevalent serious condition. Elevated suPAR above 9 ng/ml had LR+ 4.67 and a PPV of 16.7% as being predictive of 30-day mortality. Lactate was not significantly predictive.

Conclusion

Pre-hospital suPAR and lactate cannot differentiate serious conditions in need of urgent treatment and assessment in the ED among patients presenting with non-specific chief complaints. suPAR has shown to be predictive of 30-day mortality, which could add some value to the clinical assessment.

Trial registration

NCT03089359. Registered 20 March 2017, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03089359.
Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis
Authors: Poon Wynne Hsing , Ramanathan Kollengode , Ling Ryan Ruiyang , Yang Isabelle Xiaorui , Tan Chuen Seng , Schmidt Matthieu , Shekar Kiran
Published: August 2021

Background

Prone positioning (PP) improves oxygenation and respiratory mechanics and is associated with lower mortality in patients with moderate to severe acute respiratory distress syndrome (ARDS). Despite this, some patients develop refractory hypoxemia and hypercapnia requiring venovenous extracorporeal membrane oxygenation (VV ECMO) support and are usually cared for in supine position. The physiologic and outcome benefits of routine PP of patients during VV ECMO remains unclear. Hence, we conducted the systematic review and meta-analysis to evaluate the outcome benefits of PP for patients with ARDS being treated with VV ECMO.

Methods

After registration with PROSPERO (CRD42020199723), MEDLINE, EMBASE, Scopus and Cochrane databases were searched for relevant studies that reported PP in more than 10 adult patients supported with VV ECMO from origin to 1 March 2021. Studies were reviewed for quality using appropriate Joanna Briggs Institute (JBI) checklists, and certainty of evidence was assessed using the GRADE approach. The random-effects model (DerSimonian and Laird) was used. The primary outcome of interest was cumulative survival. Secondary outcomes were intensive care unit length of stay (ICU LOS) and ECMO duration. Changes in arterial blood gas (ABG) values, ventilator mechanics and complication rates were also studied.

Results

Of 812 potentially relevant publications, 12 studies (640 patients) met our inclusion criteria. Due to overlapping study populations, 11 studies were included in the final meta-analysis. Cumulative survival in patients that underwent PP was 57% (95% CI 41.9–71.4, high certainty). Patients that underwent PP had longer ICU LOS (+ 14.5 days, 95% CI 3.4–25.7, p = 0.01) and ECMO duration (+ 9.6 days, 95% CI 5.5–13.7, p < 0.0001). After PP, patients had significantly higher PaO2/FiO2 ratio, lower PaCO2 and reduced ventilator driving pressure, and no major complications were reported.

Conclusions

PP during VV ECMO appears safe with a cumulative survival of 57% and may result in longer ECMO runs and ICU LOS. However, evidence from appropriately designed randomized trials is needed prior to widespread adoption of PP on VV ECMO.
Transition from static culture to stirred tank bioreactor for the allogeneic production of therapeutic discogenic cell spheres
Authors: Rodriguez-Granrose Daniel , Zurawski Jeff , Heaton Will , Tandeski Terry , Dulatov Galina , Highsmith Angelica Adrian , Conen Mason , Clark Garrett , Jones Amanda , Loftus Hannah , LeBaron Cameron , Scull Erin , Farhang Niloo , Erickson Isaac , Bingham Justin , Decaria Paula , Jones Nephi , Foley Kevin T. , Silverman Lara
Published: August 2021

Background

Culturing cells as cell spheres results in a tissue-like environment that drives unique cell phenotypes, making it useful for generating cell populations intended for therapeutic use. Unfortunately, common methods that utilize static suspension culture have limited scalability, making commercialization of such cell therapies challenging. Our team is developing an allogeneic cell therapy for the treatment of lumbar disc degeneration comprised of discogenic cells, which are progenitor cells expanded from human nucleus pulposus cells that are grown in a sphere configuration.

Methods

We evaluate sphere production in Erlenmeyer, horizontal axis wheel, stirred tank bioreactor, and rocking bag format. We then explore the use of ramped agitation profiles and computational fluid dynamics to overcome obstacles related to cell settling and the undesired impact of mechanical forces on cell characteristics. Finally, we grow discogenic cells in stirred tank reactors (STRs) and test outcomes in vitro (potency via aggrecan production and identity) and in vivo (rabbit model of disc degeneration).

Results

Computation fluid dynamics were used to model hydrodynamic conditions in STR systems and develop statistically significant correlations to cell attributes including potency (measured by aggrecan production), cell doublings, cell settling, and sphere size. Subsequent model-based optimization and testing resulted in growth of cells with comparable attributes to the original static process, as measured using both in vitro and in vivo models. Maximum shear rate (1/s) was maintained between scales to demonstrate feasibility in a 50 L STR (200-fold scale-up).

Conclusions

Transition of discogenic cell production from static culture to a stirred-tank bioreactor enables cell sphere production in a scalable format. This work shows significant progress towards establishing a large-scale bioprocess methodology for this novel cell therapy that can be used for other, similar cell therapies.