bluuebunny/crossref_metadata_2025 huggingface dataset:
Atraumatic restorative treatment compared to the Hall Technique for occluso-proximal carious lesions in primary molars; 36-month follow-up of a randomised control trial in a school setting
Authors: Araujo Mariana Pinheiro , Innes Nicola Patricia , Bonifácio Clarissa Calil , Hesse Daniela , Olegário Isabel Cristina , Mendes Fausto Medeiros , Raggio Daniela Prócida
Published: November 2020

Background

Atraumatic Restorative Treatment (ART) and the Hall Technique (HT) are both minimally invasive, non-aerosol generating procedures (non-AGPs). They seem to have never been directly compared, nor has the HT been studied in a non-clinical setting. This study compared the HT and ART restorations placed in a school setting after 36 months.

Methods

Children (5–10 yo) who had a primary molar with a dentinal occluso-proximal, cavitated carious lesion were allocated to the ART (selective removal) or HT arms. Primary outcome: restoration survival over 36-months (using Kaplan–Meier survival analysis, log rank test, and Cox regression). Secondary outcomes: (1) occlusal vertical dimension (OVD) (1, 2, 3, 4 weeks) and (2) child self-reported discomfort; (3) treatment acceptability (immediately following interventions); (4) Child Oral Health Related Quality of Life (OHRQoL), before treatment and after 6 months and (5) a post hoc analysis of time to tooth exfoliation (1, 6, 12, 18, 24, 30, 36 months).

Results

One-hundred and thirty-one children (ART = 65; HT = 66) were included (mean age = 8.1 ± 1.2). At 36 months, 112 (85.5%) children were followed-up. Primary outcome: restoration survival rates ART = 32.7% (SE = 0.08; 95% CI 0.17–0.47); HT = 93.4% (0.05; 0.72–0.99), p < 0.001; Secondary outcomes: (1) OVD returned to pre-treatment state within 4 weeks; (2) treatment discomfort was higher for the HT (p = 0.018); (3) over 70% of children and parents showed a high acceptability for treatments, with crown aesthetics being a concern for around 23% of parents; (4) Child OHRQoL improved after 6 months; and (5) teeth treated with the HT exfoliated earlier than those in the ART group (p = 0.007).

Conclusions

Both ART and the HT were acceptable to child participants and their parents and all parents thought both restorations protected their child’s tooth. However, the crown appearance concerned almost a quarter of parents in the HT arm. Children experienced less discomfort in the ART group. Although both treatments can be performed in a non-clinical setting and have the advantage of being non-aerosol generating procedures (non-AGPs), the HT had almost three times higher survival rates (93.4%) for restoring primary molar occluso-proximal cavities compared to ART (32.7%).

Trial registration

This trial was registered in ClinicalTrials.gov (NCT02569047), 5th October 2015. https://clinicaltrials.gov/ct2/show/study/NCT02569047?cond=Hall+Technique+Atraumatic+Rest orative+Treatment&draw=2&rank=2.
A novel method for 3D face symmetry reference plane based on weighted Procrustes analysis algorithm
Authors: Zhu Yujia , Zheng Shengwen , Yang Guosheng , Fu Xiangling , Xiao Ning , Wen Aonan , Wang Yong , Zhao Yijiao
Published: November 2020

Background

We aimed to establish a novel method, using the weighted Procrustes analysis (WPA) algorithm, which assigns weight to facial anatomical landmarks, to construct a three-dimensional facial symmetry reference plane (SRP) for mandibular deviation patients.

Methods

Three-dimensional facial SRPs were independently extracted from 15 mandibular deviation patients using both our WPA algorithm and the standard PA algorithm. A reference plane was defined to serve as the ground truth. To determine whether the WPA SRP or the PA SRP was closer to the ground truth, we measured the position error of mirrored landmarks, the facial asymmetry index (FAI) error, and the angle error for the global face and each facial third partition.

Results

The average angle error between the WPA SRP and the ground truth was 1.66 ± 0.81°, which was smaller than that between the PA SRP and the ground truth. The position error of the mirrored landmarks constructed using the WPA algorithm in the global face (3.64 ± 1.53 mm) and each facial partition was lower than that constructed using the PA algorithm. The average FAI error of the WPA SRP was − 7.77 ± 17.02 mm, which was smaller than that of the PA SRP.

Conclusions

This novel automatic algorithm, based on weighted anatomic landmarks, can provide a more adaptable SRP than the standard PA algorithm when applied to severe mandibular deviation patients and can better simulate the diagnosis strategies of clinical experts.
Assessment of oral health status and treatment needs among people of Foklyan area, Dharan, Nepal
Authors: Singh A. , Shrestha A. , Bhagat T. K. , Baral D. D.
Published: November 2020

Background

Oral diseases are a major public health problem globally due to high prevalence and significant social impact. Foklyan is a peri urban area with people belonging to indigenous population of low socioeconomic status. This study was conducted to assess the oral health status and treatment needs among the people of Foklyan area, Dharan.

Methods

Cross-sectional house to house survey was conducted on 310 randomly selected participants. The participants were stratified into five age groups as per WHO Basic Oral Health Survey Methods 1997 and further categorized by gender. WHO Oral Health Assessment form 1997, WHO oral health assessment questionnaire for adult/children 2013 and questionnaire for oral hygiene practice and cost as a treatment barrier were used. The examinations were done as per WHO standard guidelines.

Results

Most of the participants were from low socioeconomic background (71.3%). About 40% of the participants deferred dental visit due to financial burden. Although 99% of the participants brushed their teeth, there was high caries experience (DMFT: 3.18 ± 5.85; dft: 2.40 ± 2.65). Mean sextant score for bleeding was 5.58 in 35–44 years age group and 5.61 in 65–74 years age group. Tobacco consumption was seen in 70.9% of the adults. Prevalence of alcohol consumption was 58.8% among adult age groups.

Conclusion

The prevalence of dental caries, periodontal diseases, and prosthetic needs were more compared to national data. There is a need for oral health promotion in this area.
Factors associated with underrepresented minority physician scientist trainee career choices
Authors: Siebert Aisha L. , Chou Shinnyi , Toubat Omar , Adami Alexander J. , Kim Hajwa , Daye Dania , Kwan Jennifer M.
Published: November 2020

Background

Recently, there have been concerted efforts to improve racial and ethnic diversity in the physician-scientist workforce. Identifying factors associated with career choices among those underrepresented in medicine and science is a necessary first step to advance this objective. The aim of the present study was to assess the attitudes and factors associated with academic and research career interests among underrepresented predoctoral physician-scientists.

Methods

A cross-sectional 70-question survey was distributed to all predoctoral single degree (MD or DO) and dual degree (MD/PhD or DO/PhD) trainees at 32 medical schools in the United States from 2012 to 2014. Main outcomes included factors important to advancement in academic medicine, intended medical specialty, and future career plans. To test the post-hoc hypothesis of whether trainees from underrepresented groups have differing perceptions of career trajectories and obstacles than their counterparts, we evaluated responses according to self-identified race/ethnic status using Chi-square and Fisher’s exact tests. All tests were two-sided and significance level of < 0.05 was used.

Results

There were a total of 4433 responses representing all predoctoral training stages. The response rate was 27%. Most respondents were single degree trainees (MD/DO 79% vs MD/DO-PhD 21%). Most respondents self-identified as White (67%), followed by Multi-racial or Other (14.3%), Asian or Pacific Islander (10.4%), Hispanic (6%), and Black or African American (4.1%). Desired career sector, career intention, and clinical specialty interest differed across race/ethnic groups. With respect to career selection factors, anticipated non-work related responsibilities during residency were also significantly different between these groups. By multivariable regression analysis, Black or African American trainees were significantly less likely than White trainees to indicate a career in academia (OR 0.496, 95% CI 0.322–0.764) and basic research (OR 0.314, 95% CI 0.115–0.857), while Multi-racial or Other trainees were also less likely than White trainees to indicate a career in academia (OR 0.763, 95% CI 0.594–0.980).

Conclusions

These data represent the first in-depth survey of career aspirations, perceptions, and interests between demographically underrepresented and non-underrepresented predoctoral physician-scientist trainees. Our results identify key differences between these cohorts, which may guide efforts to improve diversity within the physician-scientist workforce.
Health care utilization and HIV clinical outcomes among newly enrolled patients following Affordable Care Act implementation in a California integrated health system: a longitudinal study
Authors: Satre Derek D. , Parthasarathy Sujaya , Silverberg Michael J. , Horberg Michael , Young-Wolff Kelly C. , Williams Emily C. , Volberding Paul , Campbell Cynthia I.
Published: November 2020

Background

The Affordable Care Act (ACA) has increased insurance coverage for people with HIV (PWH) in the United States. To inform health policy, it is useful to investigate how enrollment through ACA Exchanges, deductible levels, and demographic factors are associated with health care utilization and HIV clinical outcomes among individuals newly enrolled in insurance coverage following implementation of the ACA.

Methods

Among PWH newly enrolled in an integrated health care system (Kaiser Permanente Northern California) in 2014 (N = 880), we examined use of health care and modeled associations between enrollment mechanisms (enrolled in a Qualified Health Plan through the California Exchange vs. other sources), deductibles (none, $1–$999 and > = $1000), receipt of benefits from the California AIDS Drug Assistance Program (ADAP), demographic factors, and three-year patterns of health service utilization (primary care, psychiatry, substance treatment, emergency, inpatient) and HIV outcomes (CD4 counts; viral suppression at HIV RNA < 75 copies/mL).

Results

Health care use was greatest immediately after enrollment and decreased over 3 years. Those with high deductibles were less likely to use primary care (OR = 0.64, 95% CI = 0.49–0.84, p < 0.01) or psychiatry OR = 0.59, 95% CI = 0.37, 0.94, p = 0.03) than those with no deductible. Enrollment via the Exchange was associated with fewer psychiatry visits (rate ratio [RR] = 0.40, 95% CI = 0.18–0.86; p = 0.02), but ADAP was associated with more psychiatry visits (RR = 2.22, 95% CI = 1.24–4.71; p = 0.01). Those with high deductibles were less likely to have viral suppression (OR = 0.65, 95% CI = 0.42–1.00; p = 0.05), but ADAP enrollment was associated with viral suppression (OR = 2.20, 95% CI = 1.32–3.66, p < 0.01). Black (OR = 0.35, 95% CI = 0.21–0.58, p < 0.01) and Hispanic (OR = 0.50, 95% CI = 0.29–0.85, p = 0.01) PWH were less likely to be virally suppressed.

Conclusions

In this sample of PWH newly enrolled in an integrated health care system in California, findings suggest that enrollment via the Exchange and higher deductibles were negatively associated with some aspects of service utilization, high deductibles were associated with worse HIV outcomes, but support from ADAP appeared to help patients achieve viral suppression. Race/ethnic disparities remain important to address even among those with access to insurance coverage.
Health variations among breast-cancer patients from different disease states: evidence from China
Authors: Yang Qing , Yu Xuexin , Zhang Wei
Published: November 2020

Background

This study aimed to obtain health utility parameters among Chinese breast cancer patients in different disease states for subsequent health economics model. In addition, we aimed to explore the feasibility of establishing a breast cancer health utility mapping model in China.

Methods

Multiple patient-reported health attributes were assessed, including quality of life, which was measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument; health utility and self-rated health, which were measured by the EuroQol-5 Dimension-5 Level (EQ-5D-5L) questionnaire. Multivariate regression models, including a linear regression model, an ordinal logistic regression model and a Tobit model, were employed to analyze health differences among 446 breast cancer patients. Subgroup analyses were performed to examine differences in multiple dimensions of health derived from the FACT-B and EQ-5D-5L instruments. A mapping function was used to estimate health utility from quality of life. Rank correlation analyses were employed to examine the correlation between estimated and observed health utility values.

Results

A total of 446 breast cancer patients with different disease states were analyzed. The health utility values of breast cancer patients in the P state (without cancer recurrence and metastasis), R state (with cancer recurrence within a year), S state (with primary and recurrent breast cancer for the second year and above), and M state (metastatic cancer) were 0.81 (SD ± 0.23), 0.90 (SD ± 0.12), 0.78 (SD ± 0.31), and 0.74 (SD ± 0.27), respectively. There were positive correlations between all scores, including every domain of the FACT-B instrument (p < 0.001). Results from multivariate analysis suggested that patients in the R and M states had lower scores for overall quality of life (R, β = − 9.45, p < 0.01; M, β = − 6.72, p < 0.05). Patients in the M state had lower health utility values than patients in the P state (β = − 0.11, p < 0.05). Estimated health utility values, which were derived from quality of life by using a mapping function, were significantly correlated with directly measured health utility values (p < 0.001).

Conclusions

We obtained the health utility and health-related quality of life (HRQoL) scores of Chinese breast cancer patients in different disease states. Mapping health utility values from quality of life using four disease states could be feasible in health economic modelling, but the mapping function may need further revision.
Pain is a common problem in patients with ILD
Authors: Shen Qinxue , Guo Ting , Song Min , Guo Wei , Zhang Yi , Duan Wang , Peng Yating , Ni Shanshan , Ouyang Xiaoli , Peng Hong
Published: November 2020

Background

As it is less known about the prevalence and characteristics of pain in the patients with interstitial lung disease (ILD), this paper aims at determining the characteristics of the pain in the patients with ILD.

Methods

Subjects with ILD and health controls with the matched ages and genders completed Short Form McGill Pain Questionnaire (SF-MPQ) and part of the Brief Pain Inventory (BPI) Short Form to elicit the characteristics of the pain. The patients with ILD were also assessed through Pulmonary Function Test, Six Minutes Walking Test (6MWT), modified Medical Research Council Dyspnea Scale (mMRC) for state of the illness and measured health-related quality of life (HRQoL) by Short Form-36 (SF-36) and psychological associations by Hospital Anxiety and Depression Scale (HADS).

Results

A total of 63 subjects with ILD and 63 healthy controls (HC) were recruited in our study. The prevalence of the pain was 61.9% in ILD versus 25.3% in HC (P = 0.005) and the median score of the pain rank index (PRI) in ILD was higher than that in HC (P = 0.014). Chest (46.1%) accounted for the highest of overall pain locations in subjects with ILD. Associated clinical factors for pain intensity in the patients with ILD included exposure history of risk factors of ILD, with a longer distance of 6MWD (≥ 250 m), and a higher mMRC score (2–4). The patients with ILD and pain are more likely to suffer impaired HRQoL (P = 0.0014) and psychological problems (P = 0.0017, P = 0.044).

Conclusion

The pain is common in those with ILD and the pain intensity is associated with exposure history, 6MWD, and mMRC score. The patients with ILD and pain were possibly to suffer depression, anxiety, and impaired HRQoL.
Association between serum calcium and prognosis in patients with acute pulmonary embolism and the optimization of pulmonary embolism severity index
Authors: Wang Xin , Xiang Yongbo , Zhang Ting , Yang Yuqing , Sun Xuefeng , Shi Juhong
Published: November 2020

Introduction

Calcium is an important coagulation factor and hypocalcemia is related to progression and poor prognosis of many cardiopulmonary diseases. However, influence of hypocalcemia on pulmonary thromboembolism (PTE) prognosis has never been reported. This study aimed to explore its prognostic value and optimize the pulmonary embolism severity index (PESI), the widely used prognosis assessment model, based on the value.

Methods

PTE patients’ variables in PESI and other related clinical characteristics including admission serum calcium were collected. Associations between these variables and PTE mortality were assessed by logistic regression and cox analysis. Variables significantly associated with 30-day PTE mortality were included to develop a new prognosis prediction rule and then its validity was compared with PESI and simplified PESI (sPESI).

Results

496 PTE patients were included and 49.48% patients had hypocalcemia (serum calcium ≤ 2.13 mmol/L) in admission, showing higher 7-day (P = 0.021), 14-day (P = 0.002), 30-day (13.03% vs 4.98%, P = 0.002) mortalities than patients without hypocalcemia. Adjusting for variables in PESI, hypocalcemia was further revealed to be an independent predictor of 30-day mortality (P = 0.014).

The optimal prediction rule contained hypocalcemia and 5 variables in PESI and sPESI, showing higher predictive validity [sensitivity (Sen): 0.930, specificity (Spec): 0.390, area under curve (AUC): 0.800] than PESI (Sen: 0.814, Spec: 0.367, AUC: 0.716) and sPESI (Sen: 0.907, Spec: 0.216, AUC: 0.703).

Conclusions

Hypocalcemia is an independent predictor of the mortality following acute PTE. Based on hypocalcemia, the optimal prediction rule showed higher validity than PESI and sPESI.
Association between recent overnight travel and use of long-lasting insecticidal nets in rural Uganda: a prospective cohort study in Tororo
Authors: Arinaitwe Emmanuel , Nankabirwa Joaniter I. , Krezanoski Paul , Rek John , Kamya Victor , Epstein Adrienne , Rosenthal Philip J. , Drakeley Chris , Kamya Moses R. , Dorsey Grant , Staedke Sarah G.
Published: November 2020

Background

The burden of malaria in Uganda remains high, but has become increasingly heterogenous following intensified malaria control. Travel within Uganda is recognized as a risk factor for malaria, but behaviours associated with travel are not well-understood. To address this knowledge gap, malaria-relevant behaviours of cohort participants were assessed during travel and at home in Uganda.

Methods

Residents from 80 randomly selected households in Nagongera sub-county, Tororo district were enrolled into a cohort to study malaria in rural Uganda. All participants were given long-lasting insecticidal nets (LLINs) at enrolment and were evaluated every 4 weeks at the study clinic. Participants were asked if they had travelled overnight from their home, and if so, a questionnaire was administered to capture information on travel details and behaviours. Behaviour while travelling was assessed within 4 weeks following travel during the study clinic visit. Behaviour while at home was assessed using a similar questionnaire during two-weekly home visits. Behaviours while travelling vs at home were compared using log binomial regression models with generalized estimating equations adjusting for repeated measures in the same individual. Analysis of factors associated with LLIN adherence, such as destination and duration of travel, time to bed during travel, gender and age at time of travel, were assessed using log binomial regression models with generalized estimating equations adjusting for repeated measures in the same individual.

Results

Between October 2017 and October 2019, 527 participants were enrolled and assessed for travel. Of these, 123 (23.2%) reported taking 211 overnight trips; 149 (70.6%) trips were within Tororo. Participants were less likely to use LLINs when travelling than when at home (41.0% vs. 56.2%, relative risk [RR] 0.73, 95% CI 0.60–0.89, p = 0.002); this difference was noted for women (38.8% vs 59.2%, RR 0.66, 95% CI 0.52–0.83, p = 0.001) but not men (48.3% vs 46.6%, RR 0.96, 95% CI 0.67–1.40, p = 0.85). In an adjusted analysis, factors associated with LLIN use when travelling included destination (travelling to districts not receiving indoor residual spraying [IRS] 65.8% vs Tororo district 32.2%, RR 1.80, 95% CI 1.31–2.46, p < 0.001) and duration of travel (> 7 nights 60.3% vs one night 24.4%, RR 1.97, 95% CI 1.07–3.64, p = 0.03).

Conclusions

Travellers, particularly women, were less likely to use LLINs when travelling than when at home. LLIN adherence was higher among those who travelled to non-IRS districts and for more than 1 week, suggesting that perceived malaria risk influences LLIN use. Strategies are needed to raise awareness of the importance of using LLINs while travelling.
Rural–urban variation in insecticide-treated net utilization among pregnant women: evidence from 2018 Nigeria Demographic and Health Survey
Authors: Ameyaw Edward Kwabena , Adde Kenneth Setorwu , Dare Shadrach , Yaya Sanni
Published: November 2020

Background

In 2018, Nigeria accounted for the highest prevalence of malaria worldwide. Pregnant women and children under five years bear the highest risk of malaria. Geographical factors affect utilization of insecticide-treated nets (ITN), yet existing literature have paid little attention to the rural–urban dimension of ITN utilization in Nigeria. This study aimed at investigating the rural–urban variation in ITN utilization among pregnant women in Nigeria using data from the 2018 Demographic and Health Survey.

Methods

A total of 2909 pregnant women were included in the study. The prevalence of ITN utilization for rural and urban pregnant women of Nigeria were presented with descriptive statistics. Chi-square test was employed to assess the association between residence, socio-demographic characteristics and ITN utilization at 95% level of significance. Subsequently, binary logistic regression was used to assess the influence of residence on ITN utilization.

Results

Eight out of ten of the rural residents utilized ITN (86.1%) compared with 74.1% among urban residents. Relative to urban pregnant women, those in rural Nigeria had higher odds of utilizing ITNs both in the crude [cOR = 2.17, CI = 1.66–2.84] and adjusted models [aOR = 1.18, CI = 1.05–1.24]. Pregnant women aged 40–44 had lower odds of ITN utilization compared to those aged 15–19 [aOR = 0.63, CI = 0.44–0.92]. Poorer pregnant women had higher odds of ITN utilization compared with poorest pregnant women [aOR = 1.09, CI = 1.04–1.32]. Across regions, those in the south [aOR = 0.26, CI = 0.14–0.49] and south-west [aOR = 0.29, CI = 0.16–0.54] had lower odds of ITN use compared to their counterparts in the north-west region.

Conclusion

The high use of ITNs among pregnant women in Nigeria may be due to the prioritization of rural communities by previous interventions. This is a dimension worth considering to enhance the attainment of the national anti-malarial initiatives. Since possession of ITN is not a guarantee for utilization, women in urban locations need constant reminder of ITN use through messages delivered at ANC and radio advertisements. Moreover, subsequent mass ITN campaigns ought to take cognizance of variations ITN use across regions and pragmatic steps be taken to increase the availability of ITN in households since there is a moderately high use in households with at least one ITN in Nigeria.
Twenty-four-hour real-time continuous monitoring of acute focal cerebral ischemia in rabbits based on magnetic inductive phase shift
Authors: Zhao Shuang-Lin , Jin Gui , Bai Ze-Lin , Chen Jing-Bo , Li Meng-Wei , Li Gen , Zhuang Wei , Liu Yue-Ning , Qin Ming-Xin
Published: November 2020

Background

As a serious clinical disease, ischemic stroke is usually detected through magnetic resonance imaging and computed tomography. In this study, a noninvasive, non-contact, real-time continuous monitoring system was constructed on the basis of magnetic induction phase shift (MIPS) technology. The “thrombin induction method”, which conformed to the clinical pathological development process of ischemic stroke, was used to construct an acute focal cerebral ischemia model of rabbits. In the MIPS measurement, a “symmetric cancellation-type” magnetic induction sensor was used to improve the sensitivity and antijamming capability of phase detection.

Methods

A 24-h MIPS monitoring experiment was carried out on 15 rabbits (10 in the experimental group and five in the control group). Brain tissues were taken from seven rabbits for the 2% triphenyl tetrazolium chloride staining and verification of the animal model.

Results

The nonparametric independent-sample Wilcoxon rank sum test showed significant differences (p < 0.05) between the experimental group and the control group in MIPS. Results showed that the rabbit MIPS presented a declining trend at first and then an increasing trend in the experimental group, which may reflect the pathological development process of cerebral ischemic stroke. Moreover, TTC staining results showed that the focal cerebral infarction area increased with the development of time

Conclusions

Our experimental study indicated that the MIPS technology has a potential ability of differentiating the development process of cytotoxic edema from that of vasogenic edema, both of which are caused by cerebral ischemia.
The effect of exercise on anxiety in the elderly worldwide: a systematic review and meta-analysis
Authors: Kazeminia Mohsen , Salari Nader , Vaisi-Raygani Aliakbar , Jalali Rostam , Abdi Alireza , Mohammadi Masoud , Daneshkhah Alireza , Hosseinian-Far Melika , Shohaimi Shamarina
Published: November 2020

Background

Physical activity and exercise are among the most important, simplest, and cheapest approaches to anxiety treatment, especially for the elderly. Their positive effects on improvement of mental disorders in the elderly have attracted a considerable level of attention. Therefore, the present study was conducted to determine the effect of sport on reducing anxiety in the elderly using meta-analysis.

Methods

In this study, national and international databases of SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, ScienceDirect, Scopus, PubMed, and Web of Science were searched to find studies published electronically from 1999 to 2019. Heterogeneity between the collected studies was determined using the Cochran's test (Q) and I2. Due to presence of heterogeneity, the random effects model was used to estimate the standardized mean difference of sport test scores obtained from the measurement of anxiety reduction among the elderly, between the intervention group before and after the test.

Results

In this meta-analysis and systematic review, 19 papers finally met the inclusion criteria. The overall sample size of all collected studies for the meta-analysis was 841 s. Mean anxiety score before and after intervention were 38.7 ± 5.6 33.7 ± 3.4 respectively, denoting a decrease in anxiety score after intervention.

Conclusion

Results of this study indicates that Sport significantly reduces Anxiety in the Elderly. Therefore, a regular exercise program can be considered as a part of the elderly care program.
Conformational changes in myeloperoxidase induced by ubiquitin and NETs containing free ISG15 from systemic lupus erythematosus patients promote a pro-inflammatory cytokine response in CD4+ T cells
Authors: Carrillo-Vázquez Daniel Alberto , Jardón-Valadez Eduardo , Torres-Ruiz Jiram , Juárez-Vega Guillermo , Maravillas-Montero José Luis , Meza-Sánchez David Eduardo , Domínguez-López María Lilia , Varela Jorge Carlos Alcocer , Gómez-Martín Diana
Published: November 2020

Background

Neutrophil extracellular traps (NETs) from patients with systemic lupus erythematosus (SLE) are characterized by lower ubiquitylation and myeloperoxidase (MPO) as a substrate. The structural and functional effect of such modification and if there are additional post-translational modifications (PTMs) are unknown.

Methods

To assess the expression and functional role of PTMs in NETs of patients with SLE; reactivation, proliferation and cytokine production was evaluated by flow cytometry using co-cultures with dendritic cells (DC) and CD4+ from SLE patients and healthy controls. The impact of ubiquitylation on MPO was assessed by molecular dynamics. The expression of ISG15 in NETs was evaluated by immunofluorescence and Western Blot.

Results

Fifteen patients with SLE and ten healthy controls were included. In the co-cultures of CD4+ lymphocytes with DC stimulated with ubiquitylated MPO or recombinant MPO, a higher expression of IFNγ and IL-17A was found in CD4+ from SLE patients (p < 0.05). Furthermore, with DC stimulated with ubiquitylated MPO a trend towards increased expression of CD25 and Ki67 was found in lupus CD4+ lymphocytes, while the opposite was documented in controls (p < 0.05). Through molecular dynamics we found the K129-K488-K505 residues of MPO as susceptible to ubiquitylation. Ubiquitylation affects the hydration status of the HEME group depending on the residue to which it is conjugated. R239 was found near by the HEME group when the ubiquitin was in K488-K505. In addition, we found greater expression of ISG15 in the SLE NETs vs controls (p < 0.05), colocalization with H2B (r = 0.81) only in SLE samples and increased production of IFNγ in PBMCs stimulated with lupus NETs compared to healthy controls NETs.

Conclusion

The ubiquitylated MPO has a differential effect on the induction of reactivation of CD4+ lymphocytes in patients with SLE, which may be related to structural changes by ubiquitylation at the catalytic site of MPO. Besides a lower ubiquitylation pattern, NETs of patients with SLE are characterized by the expression of ISG15, and the induction of IFNγ by Th1 cells.
Complement peptide C3a receptor 1 promotes optic nerve degeneration in DBA/2J mice
Authors: Harder Jeffrey M. , Williams Pete A. , Braine Catherine E. , Yang Hongtian S. , Thomas Jocelyn M. , Foxworth Nicole E. , John Simon W. M. , Howell Gareth R.
Published: November 2020

Background

The risk of glaucoma increases significantly with age and exposure to elevated intraocular pressure, two factors linked with neuroinflammation. The complement cascade is a complex immune process with many bioactive end-products, including mediators of inflammation. Complement cascade activation has been shown in glaucoma patients and models of glaucoma. However, the function of complement-mediated inflammation in glaucoma is largely untested. Here, the complement peptide C3a receptor 1 was genetically disrupted in DBA/2J mice, an ocular hypertensive model of glaucoma, to test its contribution to neurodegeneration.

Methods

A null allele of C3ar1 was backcrossed into DBA/2J mice. Development of iris disease, ocular hypertension, optic nerve degeneration, retinal ganglion cell activity, loss of RGCs, and myeloid cell infiltration in C3ar1-deficient and sufficient DBA/2J mice were compared across multiple ages. RNA sequencing was performed on microglia from primary culture to determine global effects of C3ar1 on microglia gene expression.

Results

Deficiency in C3ar1 lowered the risk of degeneration in ocular hypertensive mice without affecting intraocular pressure elevation at 10.5 months of age. Differences were found in the percentage of mice affected, but not in individual characteristics of disease progression. The protective effect of C3ar1 deficiency was then overcome by additional aging and ocular hypertensive injury. Microglia and other myeloid-derived cells were the primary cells identified that express C3ar1. In the absence of C3ar1, microglial expression of genes associated with neuroinflammation and other immune functions were differentially expressed compared to WT. A network analysis of these data suggested that the IL10 signaling pathway is a major interaction partner of C3AR1 signaling in microglia.

Conclusions

C3AR1 was identified as a damaging neuroinflammatory factor. These data help suggest complement activation causes glaucomatous neurodegeneration through multiple mechanisms, including inflammation. Microglia and infiltrating myeloid cells expressed high levels of C3ar1 and are the primary candidates to mediate its effects. C3AR1 appeared to be a major regulator of microglia reactivity and neuroinflammatory function due to its interaction with IL10 signaling and other immune related pathways. Targeting myeloid-derived cells and C3AR1 signaling with therapies is expected to add to or improve neuroprotective therapeutic strategies.
Cryopreserved, Thin, Laser-Etched Osteochondral Allograft maintains the functional components of articular cartilage after 2 years of storage
Authors: Rorick Carolyn B. , Mitchell Jordyn A. , Bledsoe Ruth H. , Floren Michael L. , Wilkins Ross M.
Published: November 2020

Background

Despite improvements in treatment options and techniques, articular cartilage repair continues to be a challenge for orthopedic surgeons. This study provides data to support that the 2-year Cryopreserved, Thin, Laser-Etched Osteochondral Allograft (T-LE Allograft) embodies the necessary viable cells, protein signaling, and extracellular matrix (ECM) scaffold found in fresh cartilage in order to facilitate a positive clinical outcome for cartilage defect replacement and repair.

Methods

Viability testing was performed by digestion of the graft, and cells were counted using a trypan blue assay. Growth factor and ECM protein content was quantified using biochemical assays. A fixation model was introduced to assess tissue outgrowth capability and cellular metabolic activity in vitro. Histological and immunofluorescence staining were employed to confirm tissue architecture, cellular outgrowth, and presence of ECM. The effects of the T-LE Allograft to signal bone marrow-derived mesenchymal stem cell (BM-MSC) migration and chondrogenic differentiation were evaluated using in vitro co-culture assays. Immunogenicity testing was completed using flow cytometry analysis of cells obtained from digested T-LE Allografts and fresh articular cartilage.

Results

Average viability of the T-LE Allograft post-thaw was found to be 94.97 ± 3.38%, compared to 98.83 ± 0.43% for fresh articular cartilage. Explant studies from the in vitro fixation model confirmed the long-term viability and proliferative capacity of these chondrocytes. Growth factor and ECM proteins were quantified for the T-LE Allograft revealing similar profiles to fresh articular cartilage. Cellular signaling of the T-LE Allograft and fresh articular cartilage both exhibited similar outcomes in co-culture for migration and differentiation of BM-MSCs. Flow cytometry testing confirmed the T-LE Allograft is immune-privileged as it is negative for immunogenic markers and positive for chondrogenic markers.

Conclusions

Using our novel, proprietary cryopreservation method, the T-LE Allograft, retains excellent cellular viability, with native-like growth factor and ECM composition of healthy cartilage after 2 years of storage at − 80 °C. The successful cryopreservation of the T-LE Allograft alleviates the limited availably of conventionally used fresh osteochondral allograft (OCA), by providing a readily available and simple to use allograft solution. The results presented in this paper supports clinical data that the T-LE Allograft can be a successful option for repairing chondral defects.
Highly variable effect of sonication to dislodge biofilm-embedded Staphylococcus epidermidis directly quantified by epifluorescence microscopy: an in vitro model study
Authors: Sandbakken Erik T. , Witsø Eivind , Sporsheim Bjørnar , Egeberg Kjartan W. , Foss Olav A. , Hoang Linh , Bjerkan Geir , Løseth Kirsti , Bergh Kåre
Published: November 2020

Background

In cases of prosthetic joint infections, culture of sonication fluid can supplement culture of harvested tissue samples for correct microbial diagnosis. However, discrepant results regarding the increased sensitivity of sonication have been reported in several studies. To what degree bacteria embedded in biofilm are dislodged during the sonication process has to our knowledge not been fully elucidated. In the present in vitro study, we have evaluated the effect of sonication as a method to dislodge biofilm by quantitative microscopy.

Methods

We used a standard biofilm method to cover small steel plates with biofilm forming Staphylococcus epidermidis ATCC 35984 and carried out the sonication procedure according to clinical practice. By comparing area covered with biofilm before and after sonication with epifluorescence microscopy, the effect of sonication on biofilm removal was quantified. Two series of experiments were made, one with 24-h biofilm formation and another with 72-h biofilm formation.

Confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) were used to confirm whether bacteria were present after sonication. In addition, quantitative bacteriology of sonication fluid was performed.

Results

Epifluorescence microscopy enabled visualization of biofilm before and after sonication. CLSM and SEM confirmed coccoid cells on the surface after sonication. Biofilm was dislodged in a highly variable manner.

Conclusion

There is an unexpected high variation seen in the ability of sonication to dislodge biofilm-embedded S. epidermidis in this in vitro model.
Emergent surgical removal of a migrated atrial septal defect occluder: case report
Authors: Wen Bi , He Juan
Published: November 2020

Background

Atrial septal defect (ASD) closure has been widely accepted and is now routinely performed using a percutaneous approach under especially echocardiographic guidance Transesophageal echocardiography (TEE). One major complication is dislocation of occluder device during or after the device implantation. Surgical removal may be required, especially when the device stuck in the left ventricular outflow tract (LVOT).

Case introduction

A 21-year-old female was admitted to our department for percutaneous closure of secundum ASD. Percutaneous closure under the guidance of TEE was recommended for the patients. During device implantation, the TEE showed dislocation of the 22 mm ASD occluder device, stucked into the LVOT and behind the anterior mitral leaflet, producing severe LVOT obstruction Fig. 1). We herein present a safe and quick technique for surgical removal of an ASD occlude device located in the LVOT.

Conclusion

This technique provides a safe method for surgical removal of malposition and migration ASD occluder device.
The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects
Authors: Kim Yoo-Mi , Choi Jin-Ho , Kim Gu-Hwan , Sohn Young Bae , Ko Jung Min , Lee Beom Hee , Cheon Chong Kun , Lim Han Hyuk , Heo Sun-Hee , Yoo Han-Wook
Published: November 2020

Background

Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients.

Results

The study cohort included 62 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harbored the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (9%). The median age at diagnosis of the 18 patients harboring the p.G85E mutation was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3075 years.

Conclusion

The GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.
Clinical and genetic characteristics and prenatal diagnosis of patients presented GDD/ID with rare monogenic causes
Authors: Lin Liling , Zhang Ying , Pan Hong , Wang Jingmin , Qi Yu , Ma Yinan
Published: November 2020

Background

Global developmental delay/intellectual disability (GDD/ID), used to be named as mental retardation (MR), is one of the most common phenotypes in neurogenetic diseases. In this study, we described the diagnostic courses, clinical and genetic characteristics and prenatal diagnosis of a cohort with patients presented GDD/ID with monogenic causes, from the perspective of a tertiary genetic counseling and prenatal diagnostic center.

Method

We retrospectively analyzed the diagnostic courses, clinical characteristics, and genetic spectrum of patients presented GDD/ID with rare monogenic causes. We also conducted a follow-up study on prenatal diagnosis in these families. Pathogenicity of variants was interpreted by molecular geneticists and clinicians according to the guidelines of the American College of Medical Genetics and Genomics (ACMG).

Results

Among 81 patients with GDD/ID caused by rare monogenic variants it often took 0.5–4.5 years and 2–8 referrals to obtain genetic diagnoses. Devlopmental delay typically occurred before 3 years of age, and patients usually presented severe to profound GDD/ID. The most common co-existing conditions were epilepsy (58%), microcephaly (21%) and facial anomalies (17%). In total, 111 pathogenic variants were found in 62 different genes among the 81 pedigrees, and 56 variants were novel. The most common inheritance patterns in this outbred Chinese population were autosomal dominant (AD; 47%), following autosomal recessive (AR; 37%), and X-linked (XL; 16%). SCN2A, SHANK3 and STXBP1 were important causal genes. Hot-spot variants were rarely found. By the follow-up, 33 affected families, including 15, 13 and 5 families inherited in AR, AD and XL modes respectively, had undergone prenatal diagnosis. And the recurrence rates are 26.7%, 15.4% and 20% for families inherited in AR, AD, and XL patterns.

Conclusion

Patients presented with GDD/ID caused by rare single gene variants are characterized by early onset, relatively severe symptoms and great clinical variability and genetic heterogeneity. Timely referrals to genetic counseling and prenatal diagnostic laboratories are important for affected families planning to have additional children.
Responding to mental health needs of Syrian refugees in Turkey: mhGAP training impact assessment
Authors: Karaoğlan Kahiloğulları Akfer , Alataş Esra , Ertuğrul Fatmagül , Malaj Altin
Published: November 2020

Background

About 1468 Syrian and Turkish doctors, serving in primary health care, have received the mhGAP training during 2016–2019. As additional training needs were identified, MoH and WHO wanted to understand the usefulness of the training and its impact in responding to the mental health needs of Syrian refugees in Turkey.

Methods

A five component assessment was done in 2019, consisting of feedback of trainees, assessment of increase in knowledge; utilization of service; compliance to treatment guidelines and service user satisfaction. The purpose was to understand the perception of participants on the training; estimate the knowledge gained—attributable to the training; estimate the increase in mental health cases identified and treated; compliance with treatment guidelines; as well as perception of the services received by end-beneficiaries.

Results

Results indicate that most of the respondents were happy with the training, but preferred additional mhGAP training as a refresher course in the future. There was knowledge gained due to the training, 9% for the Syrian and 5% for Turkish doctors. The knowledge gained has helped the practicing doctors to be more attentive and increase the numbers of cases diagnosed after the training for almost all groups of diagnoses. Most doctors, observed during practice, comply with the guidelines shared during the training, but improvement is still needed when it comes to prescription and treatment of certain conditions. The average number of mental health cases identified increased by 38 (%27) cases in the year following the training. We observed over 70% compliance with guidelines for 9 out of 12 criteria in question. The results of the patient exit interviews indicate a high level of satisfaction with the MHPSS services provided. About 95% of beneficiaries were happy with the quality of the service, and 92% having their needs met.

Conclusions

The mhGAP training was found useful. More training should be conducted to fill in the gap in service provision and meet the mental needs of Syrian refugees in Turkey.
Functional identification of potential non-canonical N-glycosylation sites within Cav3.2 T-type calcium channels
Authors: Ficelova Vendula , Souza Ivana A. , Cmarko Leos , Gandini Maria A. , Stringer Robin N. , Zamponi Gerald W. , Weiss Norbert
Published: November 2020

Low-voltage-activated T-type calcium channels are important contributors to nervous system function. Post-translational modification of these channels has emerged as an important mechanism to control channel activity. Previous studies have documented the importance of asparagine (N)-linked glycosylation and identified several asparagine residues within the canonical consensus sequence N-X-S/T that is essential for the expression and function of Cav3.2 channels. Here, we explored the functional role of non-canonical N-glycosylation motifs in the conformation N-X-C based on site directed mutagenesis. Using a combination of electrophysiological recordings and surface biotinylation assays, we show that asparagines N345 and N1780 located in the motifs NVC and NPC, respectively, are essential for the expression of the human Cav3.2 channel in the plasma membrane. Therefore, these newly identified asparagine residues within non-canonical motifs add to those previously reported in canonical sites and suggest that N-glycosylation of Cav3.2 may also occur at non-canonical motifs to control expression of the channel in the plasma membrane. It is also the first study to report the functional importance of non-canonical N-glycosylation motifs in an ion channel.