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The decreased proportion of CD4+CD25+FOXP3+ regulatory T cells in peripheral blood of children with juvenile idiopathic arthritis and its negative correlation with cytokine level

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2022 Sep;38(9):831-836.

ABSTRACT

Objective To investigate the expression of CD4+CD25+FOXP3+regulatory T cells(Tregs), IL-6 and TNF-α in patients with juvenile idiopathic arthritis (JIA) and its clinical significance. Methods The percentages of CD4+CD25+FOXP3+ Tregs in 58 children with JIA and 40 healthy controls were detected by flow cytometry. Serum levels of IL-6 and TNF-α in each patient was detected by chemiluminescence. The correlations between the expression of CD4+CD25+FOXP3+ Tregs and IL-6, TNF-α were analyzed by pearson correlation analysis. We measured the expression level of CD4+CD25+FOXP3+regulatory T cells, IL-6 and TNF-α of 18 cases six weeks after the treatment of tocilizumab (TCZ) in order to figure out the dynamic changes using methods above. Results The percentages of CD4+CD25+FOXP3+Tregs in juvenile idiopathic arthritis were significantly lower than those in 40 healthy volunteers, while levels of IL-6 and TNF-α were significantly higher. However, no obvious difference in the levels of CD4+CD25+FOXP3+Tregs, IL-6 or TNF-α was observed between patients with systemic and poly-articular JIA. Pearson correlation analysis showed that the percentages of CD4+CD25+FOXP3+Tregs negatively correlated with the levels of IL-6 and TNF-α, while levels of IL-6 positively correlated with the levels of TNF-α. Compared with pre-treatment of TCZ, levels of CD4+CD25+FOXP3+Tregs in post-treatment markedly increased, which however were still lower than control group while the levels of IL-6 significantly decreased, yet remained higher than control group. There was no statistical difference between post and pre-treatment in the levels of TNF-α. Conclusion The percentages of CD4+CD25+FOXP3+ Tregs in peripheral blood of JIA children decreases, and it has a negative correlation with IL-6 and TNF-α. Furthermore, the levels of CD4+CD25+FOXP3+ Tregs and IL-6 are partially restored after treatment with TCZ, which may be helpful to assess the activity of systemic JIA and the efficacy of therapy.

PMID:36082714

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Can we have a second helping? A preregistered direct replication study on the neurobiological mechanisms underlying self-control

Hum Brain Mapp. 2022 Sep 9. doi: 10.1002/hbm.26065. Online ahead of print.

ABSTRACT

Self-control is of vital importance for human wellbeing. Hare et al. (2009) were among the first to provide empirical evidence on the neural correlates of self-control. This seminal study profoundly impacted theory and empirical work across multiple fields. To solidify the empirical evidence supporting self-control theory, we conducted a preregistered replication of this work. Further, we tested the robustness of the findings across analytic strategies. Participants underwent functional magnetic resonance imaging while rating 50 food items on healthiness and tastiness and making choices about food consumption. We closely replicated the original analysis pipeline and supplemented it with additional exploratory analyses to follow-up on unexpected findings and to test the sensitivity of results to key analytical choices. Our replication data provide support for the notion that decisions are associated with a value signal in ventromedial prefrontal cortex (vmPFC), which integrates relevant choice attributes to inform a final decision. We found that vmPFC activity was correlated with goal values regardless of the amount of self-control and it correlated with both taste and health in self-controllers but only taste in non-self-controllers. We did not find strong support for the hypothesized role of left dorsolateral prefrontal cortex (dlPFC) in self-control. The absence of statistically significant group differences in dlPFC activity during successful self-control in our sample contrasts with the notion that dlPFC involvement is required in order to effectively integrate longer-term goals into subjective value judgments. Exploratory analyses highlight the sensitivity of results (in terms of effect size) to the analytical strategy, for instance, concerning the approach to region-of-interest analysis.

PMID:36082693 | DOI:10.1002/hbm.26065

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Five-Year Results of Coronary Artery Bypass Grafting With or Without Carotid Endarterectomy in Patients With Asymptomatic Carotid Artery Stenosis: CABACS RCT

Stroke. 2022 Sep 9:101161STROKEAHA121037493. doi: 10.1161/STROKEAHA.121.037493. Online ahead of print.

ABSTRACT

BACKGROUND: In patients with coronary artery disease and concomitant asymptomatic severe carotid stenosis, combined simultaneous coronary artery bypass grafting (CABG) and carotid endarterectomy (CEA) has been widely performed despite lack of evidence from randomized trials. We recently showed that the risk of stroke or death within 30 days was higher following CABG+CEA compared with CABG alone. Here, we report long-term outcomes following CABG with versus without CEA.

METHODS: The CABACS (Coronary Artery Bypass Graft Surgery in Patients With Asymptomatic Carotid Stenosis Study) is a randomized, controlled, multicenter, open trial. Patients with asymptomatic severe (≥70%) carotid stenosis undergoing CABG were allocated either CABG+CEA or CABG alone, and follow-up was 5 years. Major secondary end points included nonfatal stroke or death, any death and any nonfatal stroke. Due to low recruitment, the study was stopped prematurely after randomization of 127 patients in 17 centers.

RESULTS: By 5 years, the rate of stroke or death did not significantly differ between groups (CABG+CEA 40.6% [95% CI, 0.285-0.536], CABG alone 35.0% [95% CI, 0.231-0.484]; P=0.58). Higher albeit statistically nonsignificant rates of nonfatal strokes occurred at any time following CABG+CEA versus CABG alone (1 year: 19.3% versus 7.1%, P=0.09; 5 years: 29.4% versus 18.8%, P=0.25). All-cause mortality up to 5 years was similar in both groups (CABG+CEA: 25.4% versus CABG alone: 23.3%, hazard ratio, 1.148 [95% CI, 0.560-2.353]; P=0.71). Subgroup analyses did not reveal any significant effect of age, sex, preoperative modified Rankin Scale and center on outcome events.

CONCLUSIONS: During 5-years follow-up, combined simultaneous CABG+CEA was associated with a higher albeit statistically nonsignificant rate of stroke or death compared with CABG alone. This was mainly due to a nonsignificantly higher perioperative risk following CABG+CEA. Since the power of our study was not sufficient, no significant effect of either procedure could be observed at any time during follow-up.

REGISTRATION: http://www.controlled-trials.com; ISRCTN13486906.

PMID:36082667 | DOI:10.1161/STROKEAHA.121.037493

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Development of preschool refugee children living under temporary protection status

Turk J Pediatr. 2022;64(4):683-693. doi: 10.24953/turkjped.2021.1309.

ABSTRACT

BACKGROUND: The conflict in Syria following the anti-regime demonstrations that started in March 2011 created one of the greatest humanitarian crises. The United Nations High Commissioner for Refugees (UNHCR) reports that refugee and resettlement experiences can influence the critical stages of intellectual, social, emotional and physical development of children. There is a lack of sufficient information about the prevalence of developmental delay in forcibly displaced children. In this study, we aimed to describe the impact of the Syrian crisis on the development of children after resettlement, factors that are associated with developmental problems and domains in which developmental delays are more likely to occur.

METHODS: Refugee children (n=60) between the ages of 18-72 months admitted to the Yenimahalle Community Health Center Immigrant Health Unit to receive primary health care services between 1 November 2018- 1 March 2019 were included in this study. The control group included 60 Turkish children between 18-72 months admitted to the İsmail Ulucan Family Health Center which is in the same building. Developmental assessments were conducted by the researchers using the Denver II Developmental Screening Test (DDST-II). Sociodemographic characteristics of the child, family and caregivers as well as risk factors related to development were collected using a questionnaire. The interviews with refugee families were conducted with an interpreter.

RESULTS: Developmental delay was more frequent in refugee children compared to Turkish children. The DDST-II were normal in 82.1%, questionable in 10.7% and abnormal in 7.1% of Turkish children; in the study group, 22.2% of the patients were found to be normal, 33.3% were questionable and 44.4% were abnormal. The differences were statistically significant (p < 0.05). Multiple logistic regression analysis revealed that, being a forcibly displaced refugee was the single significant risk factor for developmental delay alone. In the DDST II subdomain analysis, it was seen that high monthly income reduces the risk of caution-delay in personal-social domain. It was found that birth weight below 2500 g increased the risk of caution-delay in the fine-motor and gross-motor domain and being a forcibly displaced refugee and consanguinity increased the risk of caution -delay in the language domain.

CONCLUSIONS: This study showed that being a forcibly displaced refugee was the most important risk factor for developmental delay. We emphasized the importance of surveillance and screening development in these highrisk children as well as early intervention services.

PMID:36082642 | DOI:10.24953/turkjped.2021.1309

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Evaluation of the predictability of clinical and radiological findings in the diagnosis of malrotation

Turk J Pediatr. 2022;64(4):640-647. doi: 10.24953/turkjped.2021.5019.

ABSTRACT

BACKGROUND: To evaluate the predictability of clinical and radiological findings in the diagnosis of malrotation.

METHODS: Between 2010 and 2020, children with presumptive diagnosis of malrotation were included. The demographic features, clinical and radiological findings, operative findings and outcome were recorded. The upper gastrointestinal series (UGIS) were evaluated by two radiologists. All parameters were correlated with surgical findings to evaluate the predictability.

RESULTS: Seventy patients were included. The presenting symptom was bilious vomiting in 29 cases (41.4%), and atypical symptoms (non-bilious vomiting, food refusal, etc.) in 40 cases (57%). One of the cases (1.6%) was asymptomatic and diagnosed incidentally during UGIS. 52 cases had abdominal X-ray and 14 (26.9%) of them were normal. Doppler ultrasonography (US) (n=20) revealed evidence of malrotation in 13 cases (65%). The location of duodenojejunal junction (DJJ) in UGIS was compatible with malrotation in 33 cases. 48 (61%) cases underwent surgical exploration; 35 cases had malrotation and seven cases had midgut volvulus. Median followup time was one year (0.5-7 years). Volvulus has recurred in one case and another case operated for volvulus died because of short bowel syndrome. The statistical analysis for predictability revealed that bilious vomiting (sensitivity: 57.1%, specificity: 82.1%), Doppler US (sensitivity: 92.3%, specificity: 75%) and right-sided DJJ in UGIS (sensitivity: 96.8%, specificity: 75%) have highest predictability.

CONCLUSIONS: The bilious vomiting, Doppler US findings and right-sided DJJ have the highest predictability to confirm the diagnosis. However, presenting with atypical symptoms and having atypical or normal findings in UGIS do not rule out malrotation.

PMID:36082638 | DOI:10.24953/turkjped.2021.5019

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Imaging manifestations of neonatal necrotizing enterocolitis to predict timing of surgery

Turk J Pediatr. 2022;64(4):632-639. doi: 10.24953/turkjped.2021.5048.

ABSTRACT

BACKGROUND: To find the predictor of optimal surgical timing for neonatal necrotizing enterocolitis (NEC) patients by analyzing the risk factors of conservative treatment and surgical therapy.

METHODS: Data were collected from 184 NEC patients (Surgery, n=41; conservative treatment, n=143) between the years 2015 and 2019. Data were analyzed by univariate analysis, and multivariate binary logistic regression analysis.

RESULTS: Univariate analysis showed that statistically significant differences between the surgery and conservative treatment groups. The results of multivariate Logistic regression analysis indicated intestinal wall thickening by B-ultrasound and gestational age were independent factors to predict early surgical indications of NEC (p < 0.05). The true positive rate, false positive rate, true negative rate and false negative rate in the diagnosis of necrotic bowel perforation guided by DAAS (Duke abdominal X-ray score) ≥7 and MD7 (seven clinical metrics of metabolic derangement) ≥3 were 12.8%, 0.0%, 100.0% and 87.2%, respectively.

CONCLUSIONS: In summary, the ultrasound examination in NEC children showing thickening intestinal wall and poor intestinal peristalsis indicated for early operation.

PMID:36082637 | DOI:10.24953/turkjped.2021.5048

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Benefits and Limitations of Virtual Recruitment: Perspectives From Subspeciality Directors

Pediatrics. 2022 Sep 9:e2022056735. doi: 10.1542/peds.2022-056735. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Because of the coronavirus disease 2019 pandemic and recommendations from a range of leaders and organizations, the pediatrics subspecialty 2020 recruitment season was entirely virtual. Minimal data exist on the effect of this change to guide future strategies. The aim of this study was to understand the effects of virtual recruitment on pediatric subspecialty programs as perceived by program leaders.

METHODS: This concurrent, triangulation, mixed-methods study used a survey that was developed through an iterative (3 cycles), consensus-building, modified Delphi process and sent to all pediatric subspecialty program directors (PSPDs) between April and May 2021. Descriptive statistics and thematic analysis were used, and a conceptual framework was developed.

RESULTS: Forty-two percent (352 of 840) of PSPDs responded from 16 of the 17 pediatric (94%) subspecialties; 60% felt the virtual interview process was beneficial to their training program. A majority of respondents (72%) reported cost savings were a benefit; additional benefits included greater efficiency of time, more applicants per day, greater faculty involvement, and perceived less time away from residency for applicants. PSPDs reported a more diverse applicant pool. Without an in-person component, PSPDs worried about programs and applicants missing informative, in-person interactions and applicants missing hospital tours and visiting the city. A model based upon theory of change was developed to aid program considerations for future application cycles.

CONCLUSIONS: PSPDs identified several benefits to virtual recruitment, including ease of accommodating increased applicants with a diverse applicant pool and enhanced faculty involvement. Identified limitations included reduced interaction between the applicant and the larger institution/city.

PMID:36082609 | DOI:10.1542/peds.2022-056735

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Aging is associated with increased chromatin accessibility and reduced polymerase pausing in liver

Mol Syst Biol. 2022 Sep;18(9):e11002. doi: 10.15252/msb.202211002.

ABSTRACT

Regulation of gene expression is linked to the organization of the genome. With age, chromatin alterations occur on all levels of genome organization, accompanied by changes in the gene expression profile. However, little is known about the changes in the level of transcriptional regulation. Here, we used a multi-omics approach and integrated ATAC-, RNA- and NET-seq to identify age-related changes in the chromatin landscape of murine liver and to investigate how these are linked to transcriptional regulation. We provide the first systematic inventory of the connection between aging, chromatin accessibility, and transcriptional regulation in a whole tissue. Aging in murine liver is characterized by an increase in chromatin accessibility at promoter regions, but not in an increase in transcriptional output. Instead, aging is accompanied by a decrease in promoter-proximal pausing of RNA polymerase II (Pol II), while initiation of transcription is not decreased as assessed by RNA polymerase mapping using CUT&RUN. Based on the data reported, we propose that these age-related changes in transcriptional regulation are due to a reduced stability of the pausing complex.

PMID:36082605 | DOI:10.15252/msb.202211002

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Novel 3-phenyl-1- (alkylphenyl)-9-oxa-4-azaphenanthren-10-ones as inhibitors of some enzymes: synthesis, characterization, biological evaluation and molecular docking studies

J Biomol Struct Dyn. 2022 Sep 9:1-17. doi: 10.1080/07391102.2022.2114938. Online ahead of print.

ABSTRACT

A series of novel 3-phenyl-1-(alkylphenyl)-9-oxa-4-azaphenanthren-10-ones and (E)-1-phenyl-3-(aryl)prop-2-en-1-ones were synthesized and characterized by IR, 1H NMR, 13C spectroscopy and elemental analysis. The synthesized Compounds 5a-f were subjected to molecular docking simulation with three proteins, namely, tyrosyl-tRNA synthetase, heme oxygenase 1 and acetylcholinesterase to evaluate the antibacterial, antioxidant and acetylcholinesterase inhibition, respectively. Moreover, the docked poses of all compounds inside the proteins were subjected to further dynamic simulation through the calculation of the binding free energy using MM-GBSA analysis. Compound 5d exhibits high potential inhibition against antibacterial, antioxidant and acetylcholinesterase activities. Compounds 3d, 3f, 5a and 5d recorded an important scavenging activity in DPPH and ABTS assays. Investigation of the anti-acetylcholinesterase activity of the synthesized compounds showed that Compounds 5a and 3d are the most potent inhibitors against AchE, with percent inhibition values of 38 and 30%, respectively.Communicated by Ramaswamy H. Sarma.

PMID:36082583 | DOI:10.1080/07391102.2022.2114938

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Patients’ Attitudes Towards Medical Student Presence in Psychiatric Consultations

Ir J Psychol Med. 2022 Sep 9:1-8. doi: 10.1017/ipm.2022.40. Online ahead of print.

ABSTRACT

OBJECTIVES: Studies on patient-student relationships have to date largely focused on student attitudes. This study explores attitudes of patients with psychiatric illness in Ireland, towards medical students. Patients’ experience of consent for student involvement is an area of concern in previous studies and is also quantified here.

METHODS: This was a mixed-methods cross-sectional survey of Irish adult psychiatric patients. Quantitative analysis was carried out using SPSS 22 (Statistical Product and Service Solutions, Version 22, IBM). Differences on Likert score between groups (male/female, hospital site, past experience with students/ no experience) were analysed using ordinal logistic regression with a p-value below 0.05 being significant. Qualitative data were analysed by thematic analysis using OpenCode 4.03.

RESULTS: A total of 340 patients completed the survey. The mean age (sd) was 44.8 (16.3). 52.8% were female, 75.2% were outpatients. 24.3% had never met a medical student. Most patients were comfortable seeing students, but preferred students being passive observers. Patients with previous student experience had higher comfort levels and more positive attitudes. Although most patients (63.7%) strongly agreed they had been asked for consent, only 49.3% felt they had been given sufficient information. Qualitative data revealed preference for adequate information and notice of involvement. Patients felt pressured by student presence in certain circumstances.

CONCLUSIONS: Psychiatric patients are comfortable with students but many feel inadequately informed. Patients recognise the benefits of interacting with students. More information is needed regarding circumstances in which patients give consent to involvement with students.

PMID:36082526 | DOI:10.1017/ipm.2022.40