Tag: pubmed

Nat Commun. 2021 Nov 9;12(1):6365. doi: 10.1038/s41467-021-26576-2.

ABSTRACT

The nucleolus is the organelle for ribosome biogenesis and sensing various types of stress. However, its role in regulating stem cell fate remains unclear. Here, we present evidence that nucleolar stress induced by interfering rRNA biogenesis can drive the 2-cell stage embryo-like (2C-like) program and induce an expanded 2C-like cell population in mouse embryonic stem (mES) cells. Mechanistically, nucleolar integrity maintains normal liquid-liquid phase separation (LLPS) of the nucleolus and the formation of peri-nucleolar heterochromatin (PNH). Upon defects in rRNA biogenesis, the natural state of nucleolus LLPS is disrupted, causing dissociation of the NCL/TRIM28 complex from PNH and changes in epigenetic state and reorganization of the 3D structure of PNH, which leads to release of Dux, a 2C program transcription factor, from PNH to activate a 2C-like program. Correspondingly, embryos with rRNA biogenesis defect are unable to develop from 2-cell (2C) to 4-cell embryos, with delayed repression of 2C/ERV genes and a transcriptome skewed toward earlier cleavage embryo signatures. Our results highlight that rRNA-mediated nucleolar integrity and 3D structure reshaping of the PNH compartment regulates the fate transition of mES cells to 2C-like cells, and that rRNA biogenesis is a critical regulator during the 2-cell to 4-cell transition of murine pre-implantation embryo development.

PMID:34753899 | DOI:10.1038/s41467-021-26576-2

Appl Immunohistochem Mol Morphol. 2021 Nov 11. doi: 10.1097/PAI.0000000000000985. Online ahead of print.

ABSTRACT

The heterogeneity of programmed death-ligand 1 (PD-L1) status between core needle biopsies (CNBs) from one tumor was not well studied before. The current study attempts to find out the best index using multiple core biopsies from one tumor which can better reflect the actual PD-L1 status. Random CNB was performed in surgical specimens from 170 consecutive non-small cell lung cancer samples. Fifty-one cases (41 cases with PD-L1 positive and 10 cases with PD-L1 negative) and 216 matched CNBs were analyzed by DAKO 22C3 PharmDx Link 48 Autostainer. The PD-L1 status was compared between the surgical specimens and matched CNBs. Heterogeneity of PD-L1 status between CNBs from one tumor was observed in 56% of PD-L1 positive cases. Different tumor proportion score (TPS) statistical forms with regard to the highest, mean, median, weighted average TPS, as well as TPS showed by the longest biopsy specimen and the biopsy with most tumor volume were compared. At a cut-off of 1%, the concordance rates were 94.1%, 88.2%, 90.2%, 86.3%, 86.3%, and 86.3%; At a cut-off of 50%, the concordance rates were 92.2%, 86.3%, 84.3%, 82.4%, 82.4%, and 86.3%, respectively. The CNB with the highest TPS can best represent PD-L1 status estimated by whole surgical specimen. The highest TPS among the multiple biopsies is a robust evaluation of the PD-L1 status, but not mean TPS, at the 1% and 50% cut-offs.

PMID:34753887 | DOI:10.1097/PAI.0000000000000985

J Cardiopulm Rehabil Prev. 2021 Nov 9. doi: 10.1097/HCR.0000000000000615. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to investigate changes in exercise capacity (EC) and quality of life (QoL) of patients with ventricular assist devices (VADs) during cardiac rehabilitation (CR).

METHODS: Data from patients with VAD implantation and subsequent CR between 2007 and 2017 were analyzed retrospectively. Measures of the 6-min walk test [6MWT] distance, Functional Independence Measure [FIM], ergometry, MacNew Heart Disease Questionnaire [MNH], and Hospital Anxiety and Depression Scale [HADS] at entry and discharge were examined.

RESULTS: Data from 110 patients (age 53 ± 12 yr; male 82%) were analyzed. Patients improved during CR significantly in the 6MWT (114 ± 85 m, P < .001), ergometry (20 ± 17 W, P = .002), FIM (8 ± 7 points, P < .001), and MNH (0.8 ± 0.7 points, P < .001). Initial HADS levels were high with a mean value of 9 and did not improve during CR (-0.4 ± 5 points, P = .637). Significant differences of improvements in the 6MWT were observed between left and biventricular VAD (129 ± 90 m vs 85 ± 67 m, P = .043) as well as destination therapy and bridge-to-transplant (184 ± 88 m vs 102 ± 82 m, P = .005).

CONCLUSIONS: Patients with VAD implantation had statistically and clinically significant improvements in EC and QoL as assessed with the MNH during CR. Patients on destination therapy showed a larger benefit from CR than bridge-to-transplant patients and patients with left VAD improved more than biventricular VAD patients.

PMID:34753874 | DOI:10.1097/HCR.0000000000000615

Am J Clin Oncol. 2021 Nov 10. doi: 10.1097/COC.0000000000000874. Online ahead of print.

ABSTRACT

OBJECTIVE: Compared with radical resection alone, perioperative radiation therapy (RT) combined with neurovascular preserving surgery is the standard for the management of virgin soft-tissue sarcomas. Yet, the optimal management of a local recurrence remains unclear. We report outcomes of patients with locally recurrent soft-tissue sarcoma treated with resection and reirradiation at the University of Florida.

MATERIALS AND METHODS: We reviewed the records of patients treated with primary conservative surgery and radiation for soft-tissue sarcoma followed by salvage resection and reirradiation for a local recurrence at our institution.

RESULTS: We analyzed 23 patients treated between 1976 and 2014 (median follow-up, 46 mo). Tumor sites included: proximal extremity, 11 patients; trunk, 6; distal extremity, 5; and head and neck, 1. All patients had conservative gross total resection of their recurrent tumor, without amputation. For reirradiation, 16 patients received external-beam RT alone, 6 received external-beam RT and brachytherapy, and 1 received brachytherapy alone. Two patients received chemotherapy. After retreatment, the 5-year overall survival, cause-specific survival, local control, and distant control rates were 39%, 42%, 46%, and 60%, respectively. Ten patients experienced local recurrences, 1 experienced regional recurrence, and 9 developed distant metastases. Retreatment-related complications ranged from delayed wound healing to limb amputation; 8 patients required amputation. Only 3 patients remained disease-free at last follow-up. No statistically significant associations were found between treatment factors (eg, RT dose) and local control.

CONCLUSIONS: Achieving local control of recurrent soft-tissue sarcoma is challenging. Treatment with reoperation and reirradiation can lead to debilitating complications affecting function and quality of life.

PMID:34753882 | DOI:10.1097/COC.0000000000000874

J Craniofac Surg. 2021 Nov 9. doi: 10.1097/SCS.0000000000008373. Online ahead of print.

ABSTRACT

The purpose of this study was to investigate the type and frequency of use of treatment modalities (Tx-Mods) in patients with syndromic craniosynostosis (SC) using longitudinal follow-up data. A total of 28 patients with SC (24 Crouzon, 2 Apert, and 2 Antley-Bixler syndromes), who were treated at the Department of Orthodontics, Seoul National University Dental Hospital, Seoul, South Korea between 1998 and 2020, was included. According to the degree of midface hypoplasia (MH) at the initial visit (T1), the patients were divided into the mild-MH (78°≤SNA < 80°, n = 8), moderate-MH (76°≤SNA < 78°, n = 7), and severe-MH (SNA < 76°, n = 13) groups. T1-age and Tx-Mods, including calvarial surgery (CALS), orthopedic treatment (OPT), fixed orthodontic treatment, and midface advancement surgery in childhood (MAS-child) and adulthood (MAS-adult), were investigated. Complexity of MAS-adult was graded as follows: 0, no surgery; 1, orthognathic surgery; 2, distraction osteogenesis (DOG); 3, combination of distraction osteogenesis and orthognathic surgery. Then, statistical analysis was performed. Percentage distribution of Tx-Mods was 71.4% in CALS, 21.4% in MAS-child, 42.9% in OPT, 100% in fixed orthodontic treatment, and 89.3% in MAS-adult. 92.9% of patients underwent MAS more than once. The number of MAS increased according to the severity of MH (P < 0.05). The complexity of MAS-adult increased as T1-age and severity of MH increased (all P < 0.05); whereas it decreased when CALS and OPT were performed (all P < 0.05). However, MAS in childhood did not guarantee the avoidance of additional MAS in adulthood (P > 0.05). These findings may be used as basic guidelines for successful treatment planning and prognosis prediction in patients with SC.

PMID:34753869 | DOI:10.1097/SCS.0000000000008373

J Clin Gastroenterol. 2021 Nov 10. doi: 10.1097/MCG.0000000000001636. Online ahead of print.

ABSTRACT

BACKGROUND AND GOALS: The role of early proactive therapeutic drug level monitoring for anti-tumor necrosis factor therapies is unclear. We aimed to determine whether a week 2 serum trough level in patients with inflammatory bowel disease (IBD) using adalimumab may predict clinical outcomes.

MATERIALS AND METHODS: This was a retrospective study of consecutive IBD patients with a week 2 serum adalimumab level available. Receiver operating characteristic curve analysis was conducted to determine an optimal week 2 threshold level for adalimumab. Patients above the threshold were compared for the primary outcome of week 12 clinical remission (CR) and the secondary outcome of short-term endoscopic healing. Multivariate logistic regression analysis was performed to evaluate the relationship between week 2 adalimumab level and CR.

RESULTS: Forty-six patients had a week 2 adalimumab level performed. Receiver operating characteristic curve analysis suggested an optimal adalimumab level of 11.9 mcg/mL based on the area under the curve. Patients with week 2 adalimumab levels >11.9 mcg/mL had higher odds of week 12 CR than those with levels below or equal to this threshold (odds ratio=3.34, 95% confidence interval: 1.01-12.11, P=0.04). Other covariates were not found to have a significant association with the primary outcome. The rate of short-term endoscopic healing was numerically higher in patients with adalimumab week 2 levels above 11.9 mcg/mL; however, was not statistically significant (71.4% vs. 28.5%, P=0.11).

CONCLUSIONS: Serum adalimumab levels at week 2 appears to be a predictor of short-term CR. Further research should explore whether patients with a week 2 adalimumab level equal to or below 11.9 mcg/mL benefit from early dose optimization.

PMID:34753872 | DOI:10.1097/MCG.0000000000001636

J Craniofac Surg. 2021 Nov 9. doi: 10.1097/SCS.0000000000008344. Online ahead of print.

ABSTRACT

INTRODUCTION: Maxillofacial (MF) giant cell lesions (GCLs) are benign, often locally aggressive lesions with potential for recurrence. Systemic treatments have included interferon alpha, calcitonin, bisphosphonates, and denosumab. Sclerostin (SOST) is typically thought to be a negative regulator of bone metabolism and anti-SOST agents have been used to treat osteoporosis; however, its role in central giant cell granuloma is unknown. The purpose of this study was to evaluate the expression of SOST in MF GCLs.

MATERIALS AND METHODS: This was a retrospective study of patients with MF GCLs treated at a single institution between 1993 and 2008 with a minimum follow-up of 6 months. Representative tissue was used to create a tissue microarray and SOST immunohistochemical (IHC) staining and grading was performed. The primary outcomes were IHC staining of the stromal cells and giant cells. The secondary outcomes included correlation of IHC staining and patient predictor variables including clinically benign and aggressive lesions. All analyses were completed using univariate statistical tests.

RESULTS: A total of 37 subjects were included (29 clinically aggressive and 8 clinically benign). Sclerostin staining was present in 30 of 37 subjects (81%). Of these, 22 (60%) had stromal cell staining and 28 (76%) had giant cell staining. The presence or absence of staining, of either cell type, was not associated with aggressiveness, presence of clinical symptoms, tumor size, previous interferon therapy, previous surgery, or the race or age of the patient.

DISCUSSION: Maxillofacial GCLs have an overall high level of SOST staining; however, the role of SOST in treatment and prognosis is unknown and warrants further study.

PMID:34753866 | DOI:10.1097/SCS.0000000000008344

J Contemp Dent Pract. 2021 Aug 1;22(8):939-942.

ABSTRACT

AIM: Aim of this research was to evaluate the remineralizing potential of three different remineralizing pastes on enamel that has been demineralized.

MATERIALS AND METHODS: Sixty healthy mandibular single-rooted human premolars extracted for orthodontic reasons from subjects between 18 and 25 years of age were included in this research. An area of 4 mm × 4 mm (window) was marked on the buccal surfaces of teeth samples, coated with nail varnish except for the window, which was scrutinized for changes in the values subsequent to demineralization as well as remineralization. Samples were kept in demineralizing solution for 96 hours to produce the artificial lesion in the enamel. Consequent to this process of demineralization, the 60 premolar teeth were randomly allocated to the following three groups (20 in each group) depending on the remineralizing paste used for application as group I: bioactive glass constituting remineralizing paste; group II: tricalcium phosphate (TCP) comprising remineralizing paste; and group III: calcium sucrose phosphate (CaSP) remineralizing paste. Following the pH-cycling process, the confocal laser scanning microscope was used to assess the area of demineralization and remineralization.

RESULTS: The mean areas of demineralization were slightly more (133.24 ± 0.09) in the remineralization paste comprising bioactive glass seconded by the remineralization paste having CaSP (131.39 ± 0.18), and lastly the remineralizing paste constituting TCP (129.59 ± 0.14). Maximum areas of remineralization were found in the pastes that had CaSP group (96.14 ± 0.04), next by the paste having bioactive glass group (102.18 ± 0.17), and then the remineralization paste constituting TCP (118.37 ± 0.21). The difference was statistically significant among the three remineralization pastes used.

CONCLUSION: Amid the confines of this in vitro research, a conclusion that the remineralization pastes comprising CaSP exhibited enhanced remineralization capacity in comparison to the group having bioactive glass and TCP was established.

CLINICAL SIGNIFICANCE: Caries is a highly prevalent multifactorial disease, but its progression can be prevented in the initial stage of demineralization through remineralization. Significantly increasing attention to the treatment of carious lesions that are not cavitated by employing noninvasive remineralization methods to achieve restoration of enamel has been rendered in the field of research.

PMID:34753848

J Contemp Dent Pract. 2021 Aug 1;22(8):922-927.

ABSTRACT

AIM: To analyze the clinical effectiveness of three new gingival retraction systems: knitted retraction cord, expanding polyvinyl siloxane, and aluminium chloride containing paste.

MATERIALS AND METHODS: Twenty patients were enrolled with age-group of more than 18 years and who required fixed prosthesis with minimum of two abutments. A preliminary impression of the arch was made with a stock metal tray and irreversible hydrocolloid impression material. Group WR-impression without retraction, Group A-impression after retraction with gingival retraction cord, Group B-impression after retraction with expanding polyvinyl siloxane, and Group C-impression after retraction with aluminium chloride containing paste. A total of four impressions were made for each abutment tooth. Each impression was given a label 1WR, 1A, 1B, 1C-20WR, 20A, 20B, 20C: where 1 denoted the sample number. Comparison of the stereomicroscopic images was done using image analysis software. Time required from start of placement of gingival displacement agents till completion was recorded in seconds with the help of a stop clock.

RESULTS: The mean gingival retraction was found to be the highest for subjects of Group C followed by Group A, Group B, and Group WR. This difference was found to be statistically significant. Highly significant mean difference in time of placement was observed between Group A and Group B, between Group B and Group C, and between Group C and Group A.

CONCLUSION: The aluminium chloride containing paste was found effective in almost all the variables considered.

CLINICAL SIGNIFICANCE: The choice of particular gingival retraction system/technique is dependent upon the clinical variables and on operator’s preference.

PMID:34753845

J Contemp Dent Pract. 2021 Aug 1;22(8):933-938.

ABSTRACT

AIM AND OBJECTIVE: This study aims to investigate the association between parity and dental caries among US women.

MATERIALS AND METHODS: National Health and Nutrition Examination Survey (NHANES 2001-2004) data for parous women aged 20-45 years were used for our analysis (n = 1,914). The association between parity (number of pregnancies resulted in live births) and caries experience [the decayed, missing, and filling teeth (DMFT) index] was analyzed using bivariate and multivariate regression analyses. SAS software version 9.1 was used for the statistical analyses. We used survey procedures (e.g., SURVEYFREQ, SURVEYMEANS, and SURVEYREG) that incorporate information on the appropriate weights to account for NHANES’s complex sampling design.

RESULTS: The bivariate analysis showed a trend of increase in dental caries experience among parous women as the number of live births increased (p = 0.007). After adjusting for confounders, such as age, socioeconomic status (SES), dental care coverage, and utilization, a significant association was still observed between parity level and dental caries experience (p = 0.009).

CONCLUSION: Our results suggest that higher parity can be associated with dental caries experience among US women of reproductive age.

CLINICAL SIGNIFICANCE: Clinicians should be aware of this finding to promote better oral health care and education among women with increased parity.

PMID:34753847