bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of online knowledge base in primary health care and correlation to health care quality: an observational study
Authors: Gerdesköld Christian , Toth-Pal Eva , Wårdh Inger , Nilsson Gunnar H. , Nager Anna
Published: November 2020

Background

Evidence-based information available at the point of care improves patient care outcomes. Online knowledge bases can increase the application of evidence-based medicine and influence patient outcome data which may be captured in quality registries. The aim of this study was to explore the effect of use of an online knowledge base on patient experiences and health care quality.

Methods

The study was conducted as a retrospective, observational study of 24 primary health care centers in Sweden exploring their use of an online knowledge base. Frequency of use was compared to patient outcomes in two national quality registries. A socio-economic Care Need Index was applied to assess whether the burden of care influenced the results from those quality registries. Non-parametric statistical methods and linear regression were used.

Results

Frequency of knowledge base use showed two groups: frequent and non-frequent users, with a significant use difference between the groups (p < 0.001). Outcome data showed significant higher values for all seven National Primary Care Patient Survey dimensions in the frequent compared to the non-frequent knowledge base users (p < 0.001), whereas 10 out of 11 parameters in the National Diabetes Register showed no differences between the groups (p > 0.05). Adjusting for Care Need Index had almost no effect on the outcomes for the groups.

Conclusions

Frequent users of a national online knowledge base received higher ratings on patient experiences, but figures on health care quality in diabetes showed near to no correlation. The findings indicate that some effects may be attributed to the use of knowledge bases and requires a controlled evaluation.
Intervention to improve quality of sleep of palliative patient carers in the community: protocol for a multicentre randomised controlled trial
Authors: Valero-Cantero Inmaculada , Carrión-Velasco Yolanda , Casals Cristina , Martínez-Valero Francisco Javier , Barón-López Francisco Javier , Vázquez-Sánchez María Ángeles
Published: November 2020

Background

Sleep disorders are commonly experienced by community caregivers for persons with cancer, with at least 72% reporting moderate to severe disorders. A consequence of this condition, which is associated with the presence of overload in the caregiver, is the increased risk of clinical depression. The aim of this study is to evaluate the effects of music on the sleep quality achieved by informal caregivers for cancer patients receiving home palliative care. In addition, we will assess the influence of specific variables that could modify these effects, analyse the correlates related to nocturnal wakefulness and consider the diurnal consequences according to the sleep characteristics identified.

Methods

This single-blind, multicentre, randomised clinical trial will focus on informal providers of care for cancer patients. Two samples of 40 caregivers will be recruited. The first, intervention, group will receive seven music-based sessions. The control group will be masked with seven sessions of therapeutic education (reinforcing previous sessions). Outcomes will be evaluated using the Pittsburgh Sleep Quality Index, a triaxial accelerometer, EuroQol-5D-5L, the Caregiver Strain Index, the Epworth Sleepiness Scale and the Client Satisfaction Questionnaire. The caregivers’ satisfaction with the intervention performed will also be examined.

Discussion

This study is expected to extend our understanding of the efficacy of music therapy in enhancing the sleep quality of caregivers for patients receiving home palliative care. To our knowledge, no reliable scientific investigations of this subject have previously been undertaken. Music is believed to benefit certain aspects of sleep, but this has yet to be proven and, according to a Cochrane review, high-quality research in this field is necessary. One of the main strengths of our study, which heightens the quality of the randomised clinical trial design, is the objective assessment of physical activity by accelerometry and the use of both objective and subjective measures of sleep in caregivers. Music therapy for the caregivers addressed in this study is complementary, readily applicable, provokes no harmful side effects and may produce significant benefits.

Trial registration

The IMECA study is registered at Clinical Trials.gov, ClinicalTrials.gov Identifier: NCT04491110. Registered 29 July, 2020.
The compound role of a coordinator for home-dwelling persons with dementia and their informal caregivers: qualitative study
Authors: Fæø Stein Erik , Tranvåg Oscar , Samdal Rune , Husebo Bettina S. , Bruvik Frøydis K.
Published: November 2020

Background

As the number of persons with dementia is increasing, there has been a call for establishing sustainable clinical pathways for coordinating care and support for this group. The LIVE@Home.Path trial is a multicomponent, multi-disciplinary intervention combining learning, innovation, volunteer support and empowerment. To implement the intervention, a municipal coordinator has a crucial role. Implementation research on multicomponent interventions is complex and we conducted a qualitative study, aiming to explore the coordinator role and how a coordinator may empower persons with dementia in decision-making processes.

Methods

Qualitative program evaluation combined with a hermeneutic interpretive approach was chosen as methodological approach. Sixteen dyads, consisting of the person with dementia and their main informal caregiver received the intervention by two coordinators. Of these, six dyads, three informal caregivers alone and the two care coordinators along with their leader, in sum, eighteen persons, participated in in-depth or focus group interviews, sharing their experiences after 6 months intervention.

Results

We found that the coordinators fulfilled three functions for the participating dyads: being a safety net, meaning that the dyads might have little needs at the moment, but found safety in a relation to someone who might help if the situation should change; being a pathfinder, meaning that they supported the dyads in finding their way through the complicated system of care and support services; being a source for emotional care and support, meaning that they listened, acknowledged and gave counsel in times of distress. The coordinators emphasized that a trusting leader and work environment was crucial for them to fulfill these functions. We also found that it was challenging for the coordinators to build a relation to the persons with dementia in order to pursue genuine empowerment in decision-making processes.

Conclusion

We found the framework for follow-up to be a feasible starting point for establishing empowering coordination and a sustainable care pathway for persons with dementia and their informal caregivers. More meeting points between coordinator and person with dementia should be pursued in order to fulfill the persons’ fundamental rights to participate in decision-making processes.
Parental income as a marker for socioeconomic position during childhood and later risk of developing a secondary care-diagnosed mental disorder examined across the full diagnostic spectrum: a national cohort study
Authors: Hakulinen Christian , Mok Pearl L. H. , Horsdal Henriette Thisted , Pedersen Carsten B. , Mortensen Preben B. , Agerbo Esben , Webb Roger T.
Published: November 2020

Background

Links between parental socioeconomic position during childhood and subsequent risks of developing mental disorders have rarely been examined across the diagnostic spectrum. We conducted a comprehensive analysis of parental income level, including income mobility, during childhood and risks for developing mental disorders diagnosed in secondary care in young adulthood.

Methods

National cohort study of persons born in Denmark 1980–2000 (N = 1,051,265). Parental income was measured during birth year and at ages 5, 10 and 15. Follow-up began from 15th birthday until mental disorder diagnosis or 31 December 2016, whichever occurred first. Hazard ratios and cumulative incidence were estimated.

Results

A quarter (25.2%; 95% CI 24.8–25.6%) of children born in the lowest income quintile families will have a secondary care-diagnosed mental disorder by age 37, versus 13.5% (13.2–13.9%) of those born in the highest income quintile. Longer time spent living in low-income families was associated with higher risks of developing mental disorders. Associations were strongest for substance misuse and personality disorders and weaker for mood disorders and anxiety/somatoform disorders. An exception was eating disorders, with low parental income being associated with attenuated risk. For all diagnostic categories examined except for eating disorders, downward socioeconomic mobility was linked with higher subsequent risk and upward socioeconomic mobility with lower subsequent risk of developing mental disorders.

Conclusions

Except for eating disorders, low parental income during childhood is associated with subsequent increased risk of mental disorders diagnosed in secondary care across the diagnostic spectrum. Early interventions to mitigate the disadvantages linked with low income, and better opportunities for upward socioeconomic mobility could reduce social and mental health inequalities.
Prognostic impact of the atherogenic index of plasma in type 2 diabetes mellitus patients with acute coronary syndrome undergoing percutaneous coronary intervention
Authors: Ma Xiaoteng , Sun Yan , Cheng Yujing , Shen Hua , Gao Fei , Qi Jing , Yang Lixia , Wang Zhijian , Shi Dongmei , Liu Yuyang , Liu Xiaoli , Zhou Yujie
Published: November 2020

Background

The association of the atherogenic index of plasma (AIP), an emerging lipid index that can predict the risk for cardiovascular disease, with adverse outcomes in type 2 diabetes mellitus (T2DM) patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has not been determined. Therefore, the aim of this study was to investigate whether the AIP could independently predict adverse cardiovascular events in T2DM patients with ACS undergoing PCI.

Methods

This study was a retrospective analysis of a single-centre prospective registry involving 826 consecutive T2DM patients who underwent primary or elective PCI for ACS from June 2016 to November 2017. This study ultimately included 798 patients (age, 61 ± 10 years; male, 72.7%). The AIP was calculated as the base 10 logarithm of the ratio of the plasma concentration of triglycerides to high-density lipoprotein-cholesterol (HDL-C). All the patients were divided into 4 groups based on the AIP quartiles. The primary endpoint was a composite of death from any cause, non-fatal spontaneous myocardial infarction (MI), non-fatal ischaemic stroke, and unplanned repeat revascularization. The key secondary endpoint was a composite of cardiovascular death, non-fatal MI, and non-fatal ischaemic stroke.

Results

During a median follow-up period of 927 days, 198 patients developed at least one event. An unadjusted Kaplan-Meier analysis showed that the incidence of the primary endpoint increased gradually with rising AIP quartiles (log-rank test,P = 0.001). A multivariate Cox proportional hazards analysis revealed that compared with the lowest AIP quartile, the top AIP quartile was associated with significantly increased risk for the primary and key secondary endpoints (hazard ratio [HR]: 2.249, 95% confidence interval [CI]: 1.438 to 3.517,P < 0.001; and HR: 2.571, 95% CI: 1.027 to 6.440,P = 0.044, respectively).

Conclusions

A higher AIPvalue on admission was independently and strongly associated with adverse cardiovascular events in T2DM patients with ACS undergoing PCI.
Calibration of the food parenting practice (FPP) item bank: tools for improving the measurement of food parenting practices of parents of 5–12-year-old children
Authors: Mâsse Louise C. , O’Connor Teresia M. , Lin Yingyi , Hughes Sheryl O. , Tugault-Lafleur Claire N. , Baranowski Tom , Beauchamp Mark R.
Published: November 2020

Purpose

There has been a call to improve measurement rigour and standardization of food parenting practices measures, as well as aligning the measurement of food parenting practices with the parenting literature. Drawing from an expert-informed conceptual framework assessing three key domains of food parenting practices (autonomy promotion, control, and structure), this study combined factor analytic methods with Item Response Modeling (IRM) methodology to psychometrically validate responses to the Food Parenting Practice item bank.

Methods

A sample of 799 Canadian parents of 5–12-year-old children completed the Food Parenting Practice item bank (129 items measuring 17 constructs). The factorial structure of the responses to the item bank was assessed with confirmatory factor analysis (CFA), confirmatory bi-factor item analysis, and IRM. Following these analyses, differential Item Functioning (DIF) and Differential Response Functioning (DRF) analyses were then used to test invariance properties by parents’ sex, income and ethnicity. Finally, the efficiency of the item bank was examined using computerized adaptive testing simulations to identify the items to include in a short form.

Results

Overall, the expert-informed conceptual framework was predominantly supported by the CFA as it retained the same 17 constructs included in the conceptual framework with the exception of the access/availability and permissive constructs which were respectively renamed covert control and accommodating the child to better reflect the content of the final solution. The bi-factor item analyses and IRM analyses revealed that the solution could be simplified to 11 unidimensional constructs and the full item bank included 86-items (empirical reliability from 0.78 to 0.96, except for 1 construct) and the short form had 48 items.

Conclusion

Overall the food parenting practice item bank has excellent psychometric properties. The item bank includes an expanded version and short version to meet various study needs. This study provides more efficient tools for assessing how food parenting practices influence child dietary behaviours. Next steps are to use the IRM calibrated item bank and draw on computerized adaptive testing methodology to administer the item bank and provide flexibility in item selection.
Molecular epidemiology of human papillomavirus among HIV infected women in developing countries: systematic review and meta-analysis
Authors: Bogale Agajie Likie , Belay Nega Berhe , Medhin Girmay , Ali Jemal Haidar
Published: November 2020

Background

Although, there is a variable burden of human papillomavirus (HPV) in women infected with HIV in developing countries, there are few studies that attempted to surmise such variable evidences. This review aimed to estimate the pooled prevalence of HPV genotype distribution and risk factors contributing to HPV infection among women infected with HIV in low- and middle-income countries.

Methods

We conducted a systematic review and meta-analysis of studies conducted in developing countries and reported HPV prevalence. We searched electronic databases: PubMed/Medline, SCOPUS, ScienceDirect, Excerpta Medical Database from Elsevier, Web of science, Cumulative Index of Nursing and allied Health Sciences and Google scholar databases to retrieve primary studies published in English language till 11th August 2019. We used random-effects model to estimate the pooled prevalence of HPV genotypes, and funnel plot to assess publication bias. The registration number of this review study protocol is CRD42019123549.

Results

We included nineteen studies with a total of 8,175 participants in this review. The prevalence of HPV was extremely heterogeneous across the studies (χ2=3782.80,pvalue < 0.001, I2 = 99.6%). The estimated pooled prevalence of all HPV genotypes was 63.0% (95% CI: 48.0–78.0) while the pooled prevalence of high risk and low risk HPV genotypes were 51.0% (95% CI: 38.0–63.0) and 28.0% (95% CI: 12.0–43.0), respectively. The pooled prevalence of HPV genotype 16 was 20%, while genotype 18 and 52 were 15% and 13%, respectively. Different risk factors reported for HPV infection and the frequently reported were low CD4 count below 200 cells/mm3and high HIV viral load.

Conclusion

The pooled prevalence of HPV among HIV infected women in low- and middle-income countries was considerable and the proportion of high risk HPV genotypes were high when compared with low risk genotypes. Therefore, it is essential for the HPV prevention program to prevent the double burden of HPV and HIV in women.
The recombinant pseudorabies virus expressing African swine fever virus CD2v protein is safe and effective in mice
Authors: Feng Zhihua , Chen Jianghua , Liang Wangwang , Chen Wenzhi , Li Zhaolong , Chen Qi , Cai Shaoli
Published: November 2020

Background

African swine fever (ASF) leads to high mortality in domestic pigs and wild boar and is caused by the African swine fever virus (ASFV). Currently, no vaccine is commercially available for prevention, and the epidemic is still spreading. Here, we constructed a recombinant pseudorabies virus (PRV) (PRV-ΔgE/ΔgI/ΔTK-(CD2v)) that expresses the CD2v protein of ASFV and evaluated its effectiveness and safety as a vaccine candidate in mice.

Methods

A homologous recombination fragment containing ASFV CD2v was synthesized and co-transfected into HEK 293 T cells, a knockout vector targeting the PRV TK gene. The transfected cells were infected with PRV-ΔgE/ΔgI, and the recombinant strain (PRV-ΔgE/ΔgI/ΔTK-(CD2v)) was obtained by plaque purification in Vero cells. The expression of ASFV CD2v in the recombinant virus was confirmed by sequencing, Western blotting, and immunofluorescence analysis, and the genetic stability was tested in Vero cells over 20 passages. The virulence, immunogenicity and protective ability of the recombinant virus were further tested in a mouse model.

Results

The PRV-ΔgE/ΔgI/ΔTK-(CD2v) recombinant strain is stable in Vero cells, and the processing of CD2v does not depend on ASFV infection. The vaccination of PRV-ΔgE/ΔgI/ΔTK-(CD2v) causes neither pruritus, not a systemic infection and inflammation (with the high expression of interleukin-6 (IL6)). Besides, the virus vaccination can produce anti-CD2v specific antibody and activate a specific cellular immune response, and 100% protect mice from the challenge of the virulent strain (PRV-Fa). The detoxification occurs much earlier upon the recombinant virus vaccination and the amount of detoxification is much lower as well.

Conclusions

The PRV-ΔgE/ΔgI/ΔTK-(CD2v) recombinant strain has strong immunogenicity, is safe and effective, and maybe a potential vaccine candidate for the prevention of ASF and Pseudorabies.
Special foods and local herbs used to enhance breastmilk production in Ghana: rate of use and beliefs of efficacy
Authors: Ali Zakari , Bukari Mohammed , Mwinisonaam Anita , Abdul-Rahaman Abdul-Latif , Abizari Abdul-Razak
Published: November 2020

Background

Inadequate breastmilk production is one of the key factors associated with suboptimal breastfeeding. In most local African homes, special herbs and some food items are commonly used to promote breastmilk production (known as lactogogue/galactogogue). We describe the use and characterize the herbs and food items used to promote breastmilk production in two regions of Ghana.

Methods

We conducted a cross-sectional study in 2018 involving 402 lactating mothers. The range of foods used as lactogogues was obtained from 20 participants through focus group discussions. Quantitative data on demographics, lactogogue use and feeding practices were obtained through questionnaire administration.

Results

The mean age of women was 29.2 years and children were 10 months. Breastmilk production problems were low (22.4%) and the majority of lactating mothers felt they had adequate breastmilk (70.4%) but awareness about lactogogues was widespread in both regions (88.8%) and highest in the Brong-Ahafo region (90.0%). Information about lactogogues was mainly from grandparents (24.6%), parents (31.6), health facilities (16.5%) and friends (12.8%), while the media had little influence (< 1%). The majority of the mothers used lactogogues to enhance breastmilk production (67.7%), and a quarter of them used lactogogues because of their tradition (25.2%). Prevalence of lactogogue use was 83.8%, lactogogues were prepared separate from household meals (59.4%) and consumed one to three times a day (89.6%). Users felt the effectiveness within 24 h of use (98.5%). The most common lactogogues included; groundnut/peanut soup prepared with Bra leaves (Hibiscus sabdariffa), hot black tea, Werewere/Agushi (Citrulus colocynthis) prepared with Bra leaves, and Abemudro (a polyherbal formulation). Only 13.2% of lactating mothers also used lactogogues during pregnancy.

Conclusions

Special foods and selected herbs are widely used to enhance breastmilk production in Ghana and constitute an important part of the diet of lactating mothers. These results could contribute to understanding breastfeeding behaviours and stimulate further research into evaluating the safety and scientific efficacy of these products in Ghana.
A rare cardiac phenotype of dextrocardia observed in a fetus with 1p36 deletion syndrome and a balanced translocation: a prenatal case report
Authors: Gao Li , Zhang Junyu , Han Xu , Hu Wenjing , Sun Jinling , Tan Yuru , Zhao Xinrong , Hua Renyi , Wang Shan , Zhang Yan , Wang Yanlin , Wu Yi
Published: November 2020

Background

Chromosome 1p36 deletion syndrome is a contiguous genetic disorder with multiple congenital anomalies and mental retardation. It has been emerging as one of the most common terminal deletion syndromes in humans with the rapid utility of microarray analysis. However, the prenatal findings of 1p36 deletion syndrome are still limited. We report a fetus with 1p36 deletion and cardiac phenotype of dextrocardia, combined with a balanced translocation between chromosome 5 and 6. The phenotype of dextrocardia is rarely reported in prenatal 1p36 deletion cases.

Case presentation

We present a prenatal 1p36 deletion case with congenital heart diseases and single umbilical artery. Fetal echocardiography showed dextrocardia, ventricular septal defect and pericardial effusion. Fetal karyotype revealed a de novo balanced translocation of 46,XY,t(5;6)(q11.2;q23.3). Chromosomal microarray analysis detected a pathogenic deletion in 1p36.21p36.12, with the size of 6.38 Mb. Further whole genome sequencing revealed that the balanced translocation disrupted the EYA4 and ITGA1 genes.

Conclusions

Although congenital heart diseases are very common clinical manifestations among patients with 1p36 deletion, dextrocardia is a quite rare cardiac phenotype. This is the second case with 1p36 deletion and dextrocardia, and the first prenatally diagnosed 1p36 deletion case with dextrocardia. Our case indicates that genes in 1p36 are associated with not only heart structural anomalies, but also cardiac laterality development. Our results also imply that the EYA4 gene disrupted by the balanced translocation might be related with the cardiac development.
Quality of life, function and disability in individuals with chronic ankle symptoms: a cross‐sectional online survey
Authors: Al Mahrouqi M. M. , MacDonald D. A. , Vicenzino B. , Smith M. D.
Published: November 2020

Background

Chronic ankle conditions affect approximately 20% of Australian adults. Although there is a plethora of research on chronic hip and knee conditions, there is limited understanding of the impact of ankle problems. Thus, the significance of chronic ankle conditions is not clear. The aim of this study was to compare self‐reported function, disability, instability, physical activity and quality of life (QoL) between adults with and without ankle symptoms. A secondary aim was to explore factors associated with QoL.

Method

Individuals with symptoms of ankle pain and stiffness (symptomatic individuals) and controls with no ankle pain or stiffness (asymptomatic individuals) completed a cross‐sectional online survey. The survey included the Ankle Osteoarthritis Scale (AOS), Foot and Ankle Ability Measure (FAAM), Cumberland Ankle Instability Tool (CAIT), International Physical Activity Questionnaire (IPAQ), Assessment of QoL (AQoL‐6D), and questions about ankle injury history.

Results

A total of 394 individuals (270 symptomatic and 124 asymptomatic) with mean age of 48.8 (standard deviation (SD): 12.1) years and body mass index of 28.7 (7.7) kgm− 2 completed the survey. Standardized mean differences (SMD) were large to very large (1.45 to 3.20) for greater disability (AOS) and instability (CAIT), and poorer function (FAAM) in symptomatic compared to asymptomatic individuals. Individuals with ankle symptoms had higher body mass index and lower QoL (medium effect: SMD > 1). There were no differences in self‐report physical activity between groups. Lower activities of daily living (ADL) function (FAAM‐ADL) best explained QoL in a multiple regression model (R2 = 0.66, p = 0.001).

Conclusion

Individuals with ankle symptoms reported ankle instability, greater disability, compromised function and worse QoL compared to asymptomatic individuals. There was a strong relationship between ankle function and QoL. Ankle‐specific ability during ADL best explained the reduced QoL in individuals with ankle symptoms. Clinicians and researchers should consider ankle function as an antecedent to poorer QoL in patients who have ankle symptoms.
Predictive values of neutrophil-to-lymphocyte ratio on disease severity and mortality in COVID-19 patients: a systematic review and meta-analysis
Authors: Li Xiaoming , Liu Chao , Mao Zhi , Xiao Minglu , Wang Li , Qi Shuang , Zhou Feihu
Published: November 2020

Background

Coronavirus disease 2019 (COVID-19), a highly infectious disease, has been rapidly spreading all over the world and remains a great threat to global public health. Patients diagnosed with severe or critical cases have a poor prognosis. Hence, it is crucial for us to identify potentially severe or critical cases early and give timely treatments for targeted patients. In the clinical practice of treating patients with COVID-19, we have observed that the neutrophil-to-lymphocyte ratio (NLR) of severe patients is higher than that in mild patients. We performed this systematic review and meta-analysis to evaluate the predictive values of NLR on disease severity and mortality in patients with COVID-19.

Methods

We searched PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases to identify eligible studies (up to August 11, 2020). Two authors independently screened studies and extracted data. The methodological quality of the included studies was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).

Results

Thirteen studies involving 1579 patients reported the predictive value of NLR on disease severity. The pooled sensitivity (SEN), specificity (SPE) and area under curve (AUC) were 0.78 (95% CI 0.70–0.84), 0.78 (95% CI 0.73–0.83) and 0.85 (95% CI 0.81–0.88), respectively. Ten studies involving 2967 patients reported the predictive value of NLR on mortality. The pooled SEN, SPE and AUC were 0.83 (95% CI 0.75–0.89), 0.83 (95% CI 0.74–0.89) and 0.90 (95% CI 0.87–0.92), respectively.

Conclusions

NLR has good predictive values on disease severity and mortality in patients with COVID-19 infection. Evaluating NLR can help clinicians identify potentially severe cases early, conduct early triage and initiate effective management in time, which may reduce the overall mortality of COVID-19.

Trial registry

This meta-analysis was prospectively registered on PROSPERO database (Registration number: CRD42020203612).
RETRACTED ARTICLE: MicroRNA-15b shuttled by bone marrow mesenchymal stem cell-derived extracellular vesicles binds to WWP1 and promotes osteogenic differentiation
Authors: Li Yanhong , Wang Jing , Ma Yanchao , Du Wenjia , Feng Haijun , Feng Kai , Li Guangjie , Wang Shuanke
Published: November 2020

Background

Osteogenic differentiation is an essential process for bone regeneration involving bone marrow mesenchymal stem cells (BMSCs). BMSC-secreted extracellular vesicles (EVs) enriched with microRNAs (miRs) have vital roles to play in mediating osteogenic differentiation. Therefore, this study aimed to explore the effect of BMSC-derived EVs loaded with miR-15b on osteogenic differentiation.

Methods

Human BMSCs (hBMSCs) were cultured and treated with plasmids overexpressing or knocking down KLF2, WWP1, and miR-15b to define the role of derived EVs in osteogenic differentiation in vitro. The expression of osteogenic differentiation-related marker was measured by Western blot analysis. The interaction among miR-15b, WWP1, and ubiquitination of KLF2 was investigated by dual-luciferase reporter, immunoprecipitation, and GST pull-down assays. Moreover, EVs from hBMSCs transfected with miR-15b inhibitor (EV-miR-15b inhibitor) were injected into ovariectomized rats to verify the effect of miR-15b on bone loss in vivo.

Results

WWP1 was downregulated, and KLF2 was upregulated during osteogenic differentiation. After co-culture with EVs, miR-15b expression was elevated and WWP1 expression was reduced in hBMSCs. Upregulation of miR-15b or KLF2 or downregulation of WWP1 or NF-κB increased ALP activity and cell mineralization, as well as osteogenic differentiation-related marker expression in hBMSCs. Mechanistically, miR-15b targeted and inhibited WWP1, thus attenuating KLF2 degradation and inhibiting NF-κB activity. Co-culture of EVs increased the bone volume and trabecular number, but decreased bone loss in ovariectomized rats, which could be reversed after treatment with EV-miR-15b inhibitor.

Conclusion

Collectively, BMSC-derived EVs loaded with miR-15b promoted osteogenic differentiation by impairing WWP1-mediated KLF2 ubiquitination and inactivating the NF-κB signaling pathway.

Graphical abstract
What is the size of Australia’s sexual minority population?
Authors: Wilson Tom , Temple Jeromey , Lyons Anthony , Shalley Fiona
Published: November 2020

Objectives

The aim is to present updated estimates of the size of Australia’s sexual minority adult population (gay, lesbian, bisexual, and other sexual minority identities). No estimate of this population is currently available from the Australian Bureau of Statistics, and very little is available from other sources. We obtained data on sexual minority identities from three data collections of two national surveys of recent years. Combining averaged prevalence rates from these surveys with official Estimated Resident Population data, we produce estimates of Australia’s sexual minority population for recent years.

Results

According to percentages averaged across the three survey datasets, 3.6% of males and 3.4% of females described themselves with a minority sexual identity. When applied to Estimated Resident Populations, this gives a sexual minority population at ages 18 + in Australia of 599,500 in 2011 and 651,800 in 2016. Population estimates were also produced by sex and broad age group, revealing larger numbers and higher sexual minority percentages in the younger age groups, and smaller numbers and percentages in the oldest age group. Separate population estimates were also prepared for lesbian, gay, bisexual, and other sexual minority identities.
Predictors of short-term thrombocytopenia after transcatheter aortic valve implantation: a retrospective study at a single Japanese center
Authors: Yamada Yasutaka , Miura Daisuke , Takamori Ayako , Nogami Eijiro , Yunoki Junji , Sakaguchi Yoshiro
Published: November 2020

Objective

Thrombocytopenia is common after transcatheter aortic valve implantation (TAVI) and is associated with mortality and major complications, although the underlying mechanisms are unclear. This retrospective single-center study aimed to identify factors associated with the decrease in platelet count (DPC) after TAVI in Japanese patients. Patients with severe aortic valve stenosis who underwent transfemoral TAVI between March 2014 and August 2019 were grouped according to DPC values of < 50% or ≥ 50% (DPC = 100% × [baseline platelet count–nadir platelet count]/[baseline platelet count]). Multivariable logistic regression analysis was performed to identify factors associated with a DPC of ≥ 50%.

Results

Among the 131 patients who underwent transfemoral TAVI, 74 patients (56%) had a DPC of ≥ 50%, and 57 patients (44%) had a DPC of < 50%. Significant risk factors for a DPC of ≥ 50% were older age, lower body mass index (BMI), and use of balloon-expandable valves (BEV). The multivariable analysis revealed that a DPC of ≥ 50% was independently predicted by low BMI (adjusted odds ratio: 0.884, 95% confidence interval: 0.785–0.997; P = 0.039) and BEV use (adjusted odds ratio: 3.014, 95% confidence interval: 1.003–9.056; P = 0.045). Platelet count monitoring after TAVI, especially when using BEV devices, is essential for Japanese patients with low BMI.
TREM2 Alzheimer’s variant R47H causes similar transcriptional dysregulation to knockout, yet only subtle functional phenotypes in human iPSC-derived macrophages
Authors: Hall-Roberts Hazel , Agarwal Devika , Obst Juliane , Smith Thomas B. , Monzón-Sandoval Jimena , Di Daniel Elena , Webber Caleb , James William S. , Mead Emma , Davis John B. , Cowley Sally A.
Published: November 2020

Background

TREM2 is a microglial cell surface receptor, with risk mutations linked to Alzheimer’s disease (AD), including R47H. TREM2 signalling via SYK aids phagocytosis, chemotaxis, survival, and changes to microglial activation state. In AD mouse models, knockout (KO) of TREM2 impairs microglial clustering around amyloid and prevents microglial activation. The R47H mutation is proposed to reduce TREM2 ligand binding. We investigated cell phenotypes of the R47H mutant and TREM2 KO in a model of human microglia, and compared their transcriptional signatures, to determine the mechanism by which R47H TREM2 disrupts function.

Methods

We generated human microglia-like iPSC-macrophages (pMac) from isogenic induced pluripotent stem cell (iPSC) lines, with homozygous R47H mutation or TREM2 knockout (KO). We firstly validated the effect of the R47H mutant on TREM2 surface and subcellular localization in pMac. To assess microglial phenotypic function, we measured phagocytosis of dead neurons, cell morphology, directed migration, survival, and LPS-induced inflammation. We performed bulk RNA-seq, comparing significant differentially expressed genes (DEGs; p < 0.05) between the R47H and KO versus WT, and bioinformatically predicted potential upstream regulators of TREM2-mediated gene expression.

Results

R47H modified surface expression and shedding of TREM2, but did not impair TREM2-mediated signalling, or gross phenotypes that were dysregulated in the TREM2 KO (phagocytosis, motility, survival). However, altered gene expression in the R47H TREM2 pMac overlapped by 90% with the TREM2 KO and was characterised by dysregulation of genes involved with immunity, proliferation, activation, chemotaxis, and adhesion. Downregulated mediators of ECM adhesion included the vitronectin receptor αVβ3, and consequently, R47H TREM2 pMac adhered weakly to vitronectin compared with WT pMac. To counteract these transcriptional defects, we investigated TGFβ1, as a candidate upstream regulator. TGFβ1 failed to rescue vitronectin adhesion of pMac, although it improved αVβ3 expression.

Conclusions

The R47H mutation is not sufficient to cause gross phenotypic defects of human pMac under standard culture conditions. However, overlapping transcriptional defects with TREM2 KO supports the hypothesised partial loss-of-function effects of the R47H mutation. Furthermore, transcriptomics can guide us to more subtle phenotypic defects in the R47H cells, such as reduced cell adhesion, and can be used to predict targets for therapeutic intervention.
Ryanodine receptor 1-related disorders: an historical perspective and proposal for a unified nomenclature
Authors: Lawal Tokunbor A. , Todd Joshua J. , Witherspoon Jessica W. , Bönnemann Carsten G. , Dowling James J. , Hamilton Susan L. , Meilleur Katherine G. , Dirksen Robert T.
Published: November 2020

TheRYR1gene, which encodes the sarcoplasmic reticulum calcium release channel or type 1 ryanodine receptor (RyR1) of skeletal muscle, was sequenced in 1988 andRYR1variations that impair calcium homeostasis and increase susceptibility to malignant hyperthermia were first identified in 1991. Since then,RYR1-related myopathies (RYR1-RM) have been described as rare, histopathologically and clinically heterogeneous, and slowly progressive neuromuscular disorders.RYR1variants can lead to dysfunctional RyR1-mediated calcium release, malignant hyperthermia susceptibility, elevated oxidative stress, deleterious post-translational modifications, and decreased RyR1 expression.RYR1-RM-affected individuals can present with delayed motor milestones, contractures, scoliosis, ophthalmoplegia, and respiratory insufficiency.

Historically,RYR1-RM-affected individuals were diagnosed based on morphologic features observed in muscle biopsies including central cores, cores and rods, central nuclei, fiber type disproportion, and multi-minicores. However, these histopathologic features are not always specific toRYR1-RM and often change over time. As additional phenotypes were associated withRYR1variations (including King-Denborough syndrome, exercise-induced rhabdomyolysis, lethal multiple pterygium syndrome, adult-onset distal myopathy, atypical periodic paralysis with or without myalgia, mild calf-predominant myopathy, and dusty core disease) the overlap among diagnostic categories is ever increasing. With the continuing emergence of new clinical subtypes along theRYR1disease spectrum and reports of adult-onset phenotypes, nuanced nomenclatures have been reported (RYR1- [related, related congenital, congenital] myopathies). In this narrative review, we provide historical highlights ofRYR1research, accounts of the main diagnostic disease subtypes and proposeRYR1-related disorders (RYR1-RD) as a unified nomenclature to describe this complex and evolving disease spectrum.
MyoSight—semi-automated image analysis of skeletal muscle cross sections
Authors: Babcock Lyle W. , Hanna Amy D. , Agha Nadia H. , Hamilton Susan L.
Published: November 2020

Background

Manual analysis of cross-sectional area, fiber-type distribution, and total and centralized nuclei in skeletal muscle cross sections is tedious and time consuming, necessitating an accurate, automated method of analysis. While several excellent programs are available, our analyses of skeletal muscle disease models suggest the need for additional features and flexibility to adequately describe disease pathology. We introduce a new semi-automated analysis program, MyoSight, which is designed to facilitate image analysis of skeletal muscle cross sections and provide additional flexibility in the analyses.

Results

We describe staining and imaging methods that generate high-quality images of immunofluorescent-labelled cross sections from mouse skeletal muscle. Using these methods, we can analyze up to 5 different fluorophores in a single image, allowing simultaneous analyses of perinuclei, central nuclei, fiber size, and fiber-type distribution. MyoSight displays high reproducibility among users, and the data generated are in close agreement with data obtained from manual analyses of cross-sectional area (CSA), fiber number, fiber-type distribution, and number and localization of myonuclei. Furthermore, MyoSight clearly delineates changes in these parameters in muscle sections from a mouse model of Duchenne muscular dystrophy (mdx).

Conclusions

MyoSight is a new program based on an algorithm that can be optimized by the user to obtain highly accurate fiber size, fiber-type identification, and perinuclei and central nuclei per fiber measurements. MyoSight combines features available separately in other programs, is user friendly, and provides visual outputs that allow the user to confirm the accuracy of the analyses and correct any inaccuracies. We present MyoSight as a new program to facilitate the analyses of fiber type and CSA changes arising from injury, disease, exercise, and therapeutic interventions.
Consistent independent low-rank matrix analysis for determined blind source separation
Authors: Kitamura Daichi , Yatabe Kohei
Published: November 2020

Independent low-rank matrix analysis (ILRMA) is the state-of-the-art algorithm for blind source separation (BSS) in the determined situation (the number of microphones is greater than or equal to that of source signals). ILRMA achieves a great separation performance by modeling the power spectrograms of the source signals via the nonnegative matrix factorization (NMF). Such a highly developed source model can solve the permutation problem of the frequency-domain BSS to a large extent, which is the reason for the excellence of ILRMA. In this paper, we further improve the separation performance of ILRMA by additionally considering the general structure of spectrograms, which is calledconsistency, and hence, we call the proposed methodConsistent ILRMA. Since a spectrogram is calculated by an overlapping window (and a window function induces spectral smearing called main- and side-lobes), the time-frequency bins depend on each other. In other words, the time-frequency components are related to each other via the uncertainty principle. Such co-occurrence among the spectral components can function as an assistant for solving the permutation problem, which has been demonstrated by a recent study. On the basis of these facts, we propose an algorithm for realizing Consistent ILRMA by slightly modifying the original algorithm. Its performance was extensively evaluated through experiments performed with various window lengths and shift lengths. The results indicated several tendencies of the original and proposed ILRMA that include some topics not fully discussed in the literature. For example, the proposed Consistent ILRMA tends to outperform the original ILRMA when the window length is sufficiently long compared to the reverberation time of the mixing system.
Can technology optimise the pre-operative pathway for elective hip and knee replacement surgery: a qualitative study
Authors: Sharif Faraz , Rahman Ammar , Tonner Emma , Ahmed Hanad , Haq Iqraa , Abbass Rami , Asinger Shad , Sbai Magda
Published: November 2020

Background

An ageing population has resulted in a rise in the number of hip and knee replacement surgeries in the UK. The pre-operative pathway is plagued with issues causing long delays and cancellations. Virtual healthcare technologies have a growing evidence base to help solve these issues. One problem of implementing these technologies is the resistance to change mentality from healthcare professionals. By getting their opinions on the place of these technologies within the pre-operative pathway, a united front can be formed to help deliver change.

Methods

Sixteen semi-structured interviews were conducted with key stakeholders within the orthopaedic pre-operative pathway at Imperial College Healthcare NHS Trust. General topics included the different technologies that could be used within the pathway, their uses and associated benefits and problems. Interviews were audio-recorded, before being manually transcribed and then analysed to form categories and themes.

Results

Various uses, benefits and problems were identified by healthcare professionals for each modality of technology. E-forms were seen as a high reward, low-risk intervention. Remote patient monitoring and teleconsultations had their bonuses, but feasibility was a primary concern. Web-based interventions were seen as an intervention of the past, whereas virtual reality was seen as perhaps being ahead of its time. M-health was very positively viewed due to its all-encompassing nature. Digital illiteracy emerged as a consistent problem for most technologies.

Conclusions

Current literature, the results from this study and technology trends within society highlight both M-health and E-forms as the 2 most promising virtual healthcare technologies for use in the pre-operative pathway for orthopaedics. Areas such as pre-operative assessment, triaging and prehabilitation are prime candidates for virtual intervention. Future research should also consider including patient opinions on any proposed interventions, as well as taking into account barriers to implementation.
Characterization of the materials and techniques of a birthday inscribed lacquer plaque of the Qing Dynasty
Authors: Zheng Liping , Wang Liqin , Zhao Xing , Yang Jiali , Zhang Mengxia , Wang Yunfu
Published: November 2020

In this study, in order to analyze the materials and techniques used for the production of the inscribed plaques, multi-analytical scientific approach, including optical microscopy (OM), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM–EDS), X-ray diffraction (XRD), micro-attenuated total reflection Fourier transform infrared spectroscopy (μ-ATR-FTIR), and micro-Raman spectroscopy (μ-Raman), were used to explore the materials and techniques utilized to create the “Chun Rong Xuan Mao” birthday inscribed plaque of the Qing Dynasty. The results showed that the plaque was made of cypress wood and decorative parts consisting of the surface lacquer layers, plaster lacquer layers and primer lacquer layers. Chinese lacquer was the principal material used in the surface lacquer layers; gypsum and Chinese lacquer were the materials used in the plaster lacquer layers; and the primer lacquer layers was composed of Chinese lacquer, calcite, and mixed pigments by cinnabar and minium. The surface lacquer layers of the inscribed plaque were lacquered black. Gypsum lacquer plaster has been commonly used in the ground layer of lacquerware in modern history. This study confirmed the existence of technology to make lacquerware using gypsum lacquer plaster in the Bashu area during the late Qing Dynasty. Moreover, this study not only provides new findings regarding the traditional production of inscribed plaques and offers technical support for the protection and restoration of such plaques but also has great significance to exploring the history of ancient techniques of lacquering and decorating lacquerware.