Τρίτη 19 Ιουλίου 2022

Cancer cells corrupt normal epithelial cells through miR-let-7c-rich small extracellular vesicle-mediated downregulation of p53/PTEN

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International Journal of Oral Science, Published online: 19 July 2022; doi:10.1038/s41368-022-00192-2

Cancer cells corrupt normal epithelial cells through miR-let-7c-rich small extracellular vesicle-mediated downregulation of p53/PTEN
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Comparative study of DFAT cell and ADSC sheets for periodontal tissue regeneration:in vivo and in vitro evidence

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Abstract

Aim

To compare the efficacy of adipocyte-derived dedifferentiated fat (DFAT) cell and adipose-derived stromal cell (ADSC) sheets for regenerative treatment of intrabony periodontal defects.

Material and Methods

DFAT cells were obtained using the ceiling culture method and were compared with ADSCs using Cell Counting Kit-8 (CCK8), colony formation assay, surface antigen identification, and multilineage differentiation assays. DFAT and ADSC sheets were prepared in cell sheet culture medium. The biological characteristics of DFAT cell and ADSC sheets were compared using haematoxylin and eosin staining, quantitative reverse transcription PCR, and immunofluorescence staining. Micro-computed tomography and histological staining were used to compare the effects of the two cell sheets on the repair of periodontal intrabony defects in rats.

Results

DFAT cells and ADSCs demonstrated mesenchymal stem cell characteristics. Both cell type were CD29-, CD90-, and CD146-positive and CD31-, CD34-, and CD45-negative. DFAT cells and ADSCs exhibited similar osteogenic and adipogenic differentiation capabilities, and colony-formation ability. DFAT cells displayed stronger proliferation capabilities compared to ADSCs. Compared with the ADSC sheets, DFAT cell sheets exhibited a higher expression of periodontal-related genes and proteins and greater ability to regenerate periodontal tissue.

Conclusion

Our findings suggest that DFAT cell sheets are an ideal seed cell source and form of cell delivery for periodontal intrabony defects.

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The accuracies of three intraoral scanners with regards to shade determination: An in vitro study

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Abstract

Purpose

: To compare the accuracy of three intraoral scanners for shade determination function in vitro, and to preliminarily investigate the shade-matching characteristics of the three intraoral scanners.

Materials & Methods

The shade of the middle third region of each shade tab on the Vita Classical A1-D4 shade guide (VC) was measured by a spectrophotometer (Vita Easyshade V, VE) and three intraoral scanners, including CEREC Omnicam (OM), 3Shape TRIOS 3 (T3), and TRIOS 4 (T4). A conversion table between VC values and CIELAB values was established from the database of VE to analyze the trueness. The reproducibility of the instruments was then compared by repeating the measurements five times.

Results

: The mean color difference for each instrument was highest in the OM, followed by the T4, and lowest in the T3 and VE, repectively. The L* and a* value for OM, and the b* value for T4, were significantly different from those for VE (p <0.05). The reproducibility of the instrument was highest in the VE (Fleiss' kappa: 0.95), followed by the T3 (Fleiss' kappa: 0.89), T4 (Fleiss' kappa: 0.87), and OM (Fleiss' kappa: 0.78).

Conclusions

: Of the three intraoral scanners, the trueness was best on the T3. The reproducibility of all the instruments was excellent.

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TREM2‐induced activation of microglia contributes to synaptic integrity in cognitively intact aged individuals with Alzheimer's neuropathology

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TREM2-induced activation of microglia contributes to synaptic integrity in cognitively intact aged individuals with Alzheimer's neuropathology

Efficient TREM2-phagocytic microglia underlie synaptic resilience in NDAN, removing damaged synpases, contributing to synaptic integrity and protecting from memory deficits.


Abstract

The existence of individuals who remain cognitively intact despite presenting histopathological signs of Alzheimer's disease (AD), here referred to as "Nondemented with AD neuropathology" (NDAN), suggests that some mechanisms are triggered to resist cognitive impairment. Exposed phosphatidylserine (ePS) represents a neuronal "eat-me" signal involved in microglial-mediated phagocytosis of damaged synapses. A possible mediator of this process is TREM2, a microglial surface receptor activated by ligands including PS. Based on TREM2 role in the scavenging function of microglia, we hypothesize that an efficient microglial phagocytosis of damaged synapses underlies synaptic resilience in NDAN, thus protecting from memory deficits. Using immunofluorescence microscopy, we performed a comparative study of human post-mortem frontal cortices of aged-matched, AD and NDAN individuals. We studied the distribution of activated microglia (IBA1, IBA1+/CD68+ cells) and phagocytic microglia-related proteins (TREM2, DAP12), demonstrating higher microglial activation and TREM2 expression in NDAN versus AD. A study of the preservation of synapses around plaques, assessed using MAP2 and βIII tubulin as dendritic and axonal markers, respectively, and PSD95 as a postsynaptic marker, revealed preserved axonal/dendritic structure around plaques in NDAN versus AD. Moreover, high levels of PSD95 around NDAN plaques and the colocalization of PSD95 with CD68 indicated a prompt removal of damaged synapses by phagocytic microglia. Furthermore, Annexin V assay on aged-matched, AD and NDAN individuals synaptosomes revealed increased levels of ePS in NDAN, confirming damaged synapses engulfment. Our results suggest a higher efficiency of TREM2-induced phagocytic microglia in removing damaged synapses, underlying synaptic resilience in NDAN individuals.

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A higher tumor volume and undernutrition at diagnosis adversely affect the survival of children with Wilms tumor: A study of 200 patients

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Abstract

Background

Distinct prognostic factors for Wilms tumor (WT) in low- and middle-income countries need identification.

Methods

Retrospective study of patients with WT managed by the International Society of Pediatric Oncology (SIOP) approach for over 11 years (2005–2016) at a single center in Chandigarh, India.

Results

The study included 200 patients (median age: 33.5 months). The tumor stage (SIOP) distribution included stage I (30%), II (36%), III (14%), IV (17%), and V (3%). The histology-risk groups were low (8%), intermediate (84%), and high risk (9%). At diagnosis, 68 out of 190 (36%) patients were underweight. The median tumor volume at diagnosis was 481 ml (interquartile ratio [IQR]: 306.9, 686.8, n = 146). Following neoadjuvant chemotherapy, it reduced to 110 ml (IQR: 151.2, 222, n = 77). Treatment was abandoned in 20.5% of the patients. Treatment-related mortality occurred in 13 of 179 (7.2%) patients. Relapse occurred in 26 of 158 (16.5%) patients. The 3-year overall survival (OS) and event-free survival (EFS) of patients who completed therapy were 78.3 and 72%, respectively. The stage (p = .013) and histology (p = .023) influenced OS. A lower OS in stage II (75.4%) versus stage III disease (83.7%) suggested understaging. Patients with a higher tumor volume at diagnosis (p = .005; odds ratio [OR]: 0.99; 95% confidence interval [CI]: 0.99–1.00) or a lower weight-for-age z-score (p = .002; OR: 1.68; 95% CI: 1.21–2.33) had an increased risk of death or relapse.

Conclusions

The 3-year OS and EFS of children who completed therapy were 78.3 and 72%, respectively. A higher tumor volume and lower weight-for-age z-score at diagnosis were identified as distinct adverse prognostic factors. A likely suboptimal lymph node assessment (intraoperative and histopathology) contributed to the understaging of stage III to II disease and reduced survival.

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Ridge augmentation using autologous concentrated growth factors enriched bone graft matrix versus guided bone regeneration using native collagen membrane in horizontally deficient maxilla: A randomized clinical trial

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Abstract

Background

Facial resorption of maxillary alveolar ridges is a challenging situation for implant rehabilitation, which mandates a preparatory surgery of bone augmentation. Guided bone regeneration using a 1:1 mixture of autogenous particulate and anorganic bovine bone mineral (ABBM) showed reliable outcomes in treating horizontally deficient ridges.

Methods

Twenty-eight patients were randomly assigned into two groups; in the control group, the 1:1 mixture of particulate autogenous bone and ABBM was covered with native collagen membrane, while in the study group, it was mixed with autologous fibrin glue (AFG) to make a sticky bone that was covered by concentrated growth factor (CGF) membrane. For each proposed implant site, the average bone width gain was calculated preoperatively, immediately after augmentation and after 6 months. Implants were placed after 6 months and the implant stability quotient (ISQ) was measured after insertion and after 6 more months.

Results

The graft consolidation period went uneventful in both groups; however, two cases in the sticky bone group showed total resorption of the graft upon re-entry. The mean horizontal bone width after 6 months was 9 mm ± 0.71 in the guided bone regeneration (GBR) group which was higher than 7.9 mm ± 0.92 for the sticky bone group. The mean primary stability was higher in the GBR group; 67.19 ± 2.23 compared to 66.7 ± 3.22 for the sticky bone group, while the mean secondary stability was higher in the sticky bone group; 72 ± 2.15 compared to 71.7 ± 2.27 for the GBR group. Results of Shapiro–Wilk's for bone width data and model residuals were both statistically not significant (p > 0.05).

Conclusion

Comparing CGF membrane versus native collagen membrane as barriers for GBR showed no statistically significant difference regarding bone gain. However, from a clinical point of view, CGF membrane is not a predictable barrier for guided bone regeneration.

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Camrelizumab plus chemotherapy in advanced non‐squamous non‐small cell lung cancer: Treatment response, survival pattern, and safety

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Camrelizumab plus chemotherapy in advanced non-squamous non-small cell lung cancer: Treatment response, survival pattern, and safety

This study retrospectively analysed 31 driver-gene-negative advanced non-squamous non-small cell lung cancer (NSCLC) patients who received a 21-day therapy cycle for four cycles of camrelizumab (intravenous injection, 200 mg/cycle) plus carboplatin and pemetrexed (CP) chemotherapy, followed by maintenance therapy using camrelizumab or pemetrexed or camrelizumab plus pemetrexed. Another 40 patients who underwent CP chemotherapy were retrieved as control group. Interestingly, objective response rate (ORR) was elevated in camrelizumab plus CP group compared to CP group (58.1% vs. 32.5%), while disease control rate (DCR) was of no difference between those two groups (83.9% vs. 72.5%). Camrelizumab plus CP achieved a prolonged progression-free survival (PFS) compared with CP alone (11.0 (95% CI: 9.1–12.9) months versus 7.2 (95% CI: 5.1–9.3) months), also realized an increasing overall survival (OS) trend (without statistical significance; 19.3 (95% CI: 15.4–23.2) months versu s 15.1 (95% CI: 13.9–16.3) months). Further multivariate Cox's regression analysis exhibited that camrelizumab plus CP (vs. CP) independently related to prolonged PFS and OS. Moreover, the most common adverse events related to camrelizumab plus CP were fatigue (45.2%), peripheral neuropathy (35.5%), nausea and vomiting (35.5%); furthermore, most adverse events were controllable. Collectively, camrelizumab plus chemotherapy exhibits good efficacy and manageable adverse events in treating advanced non-squamous NSCLC patients.


Abstract

What is known and objective

Camrelizumab, a humanized monoclonal programmed cell death protein-1 antibody independently developed by China, is introduced as a treatment selection for non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and safety of camrelizumab plus chemotherapy in treating advanced non-squamous NSCLC patients.

Methods

This study retrospectively analysed 31 driver-gene-negative advanced non-squamous NSCLC patients who received a 21-day therapy cycle for four cycles of camrelizumab (intravenous injection, 200 mg/cycle) plus carboplatin and pemetrexed (CP) chemotherapy, followed by maintenance therapy using camrelizumab or pemetrexed or camrelizumab plus pemetrexed. Another 40 patients who underwent CP chemotherapy were retrieved as control group.

Results and discussion

The objective response rate (ORR) was elevated in camrelizumab plus CP group compared to CP group (58.1% vs. 32.5%, p = 0.031), while disease control rate (DCR) was of no difference between those two groups (83.9% vs. 72.5%, p = 0.255). Camrelizumab plus CP achieved a prolonged PFS compared with CP alone (median: 11.0 (95% CI: 9.1–12.9) months versus 7.2 (95% CI: 5.1–9.3) months, p = 0.026), also realized an increasing OS trend (without statistical significance; 19.3 (95% CI: 15.4–23.2) months versus 15.1 (95% CI: 13.9–16.3) months, p = 0.093). Further multivariate Cox's regression analysis exhibited that camrelizumab plus CP (vs. CP) independently related to prolonged PFS (p < 0.001) and OS (p = 0.027). Moreover, the most common adverse events related to camrelizumab plus CP were fatigue (45.2%), peripheral neuropathy (35.5%), nausea and vomiting (35.5%); furthermore, most a dverse events were controllable.

What is new and conclusion

Camrelizumab plus chemotherapy exhibits good efficacy and manageable adverse events in treating advanced non-squamous NSCLC patients.

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Documentation in Pediatric Microlaryngoscopy/Bronchoscopy: International Modified Delphi Consensus

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Documentation in Pediatric Microlaryngoscopy/Bronchoscopy: International Modified Delphi Consensus

Pediatric microlaryngoscopy and bronchoscopy is a common procedure where adequate documentation is crucial for patient care and medicolegal purposes. There is significant variability in operative reports. We sought to develop an expert consensus of the key components for operative documentation, to improve patient care, communication and research.


Background

Complete and accurate documentation of surgical procedures is essential for optimizing patient care, yet significant variation in operative notes persists within and across institutions. We sought to reach consensus on the most important components of an operative note for pediatric microlaryngoscopy and bronchoscopy.

Methods

A modified Delphi consensus process was used. A checklist for operative documentation, created by fellowship-trained pediatric otolaryngologists-head and neck surgeons, was sent to surgeons identified as experts in pediatric laryngoscopy and bronchoscopy. In the first round, items were rated as "keep" or "remove". In the second round, each item was rated on a 7-point Likert scale for importance. The mean score of each item was calculated to determine if consensus was reached.

Results

Overall, 43/74 (58.1%) surgeons responded to our survey. After two rounds of editing, 28 components reached consensus, 24 were near consensus, and 26 did not reach consensus. Items that reached final consensus had mean (SD) ratings of 6.12 (0.94) (range, 5.31–6.72).

Conclusion

Pediatric otolaryngologists identified as bronchoscopy experts were able to create a checklist of essential components of an operative note for pediatric laryngoscopy and bronchoscopy using a Delphi method. Items reaching consensus included procedure name, description of breathing, grade of airway view, description of normal anatomic structures, grade of subglottic stenosis if present, presence and description of tracheobronchomalacia, presence of fistulae, cleft and rings, and several special cases including foreign body and tracheostomy management, as well as end of procedure disposition and complications.

Level of Evidence

5 Laryngoscope, 2022

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Proximal Scar Progression in Idiopathic Subglottic Stenosis After Wedge Excision: Does it Happen?

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Proximal Scar Progression in Idiopathic Subglottic Stenosis After Wedge Excision: Does it Happen?

The first study to evaluate proximal scar progression in idiopathic subglottic stenosis (iSGS) patients who have undergone CO2 laser wedge excision demonstrates a baseline glottic involvement rate of 4.5% in iSGS and low risk of glottic involvement resulting from the procedure.


Objective

To compare the incidence of glottic stenosis in idiopathic subglottic stenosis (iSGS) patients with no prior surgical intervention to those with a history of endoscopic dilation and characterize the incidence of glottic involvement, changes in scar length, and progression of scar toward glottis following laser wedge excision (LWE).

Methods

A retrospective review of iSGS patients who underwent LWE between 2002 and 2021 was performed. Patients without prior airway surgery were labeled LWE primary (LWEP) and operative findings for LWEP patients were reviewed for glottic involvement, scar length (DL), and distance from the glottis to superior-most aspect of scar (DGS). Rates (in mm/procedure) of DΔL, reflecting an increase in length, and D−ΔGS, reflecting proximal migration, were calculated by dividing DΔL and D−ΔGS by the number of LWE procedures.

Results

213 iSGS patients underwent LWE, with 132 being LWEP patients. LWEP had a lower incidence of baseline glottic involvement (n = 6, 4.5%) than LWE secondary (LWES; n = 6, 7.5%). Four new cases of glottic involvement were noted in LWEP patients following LWE, with only one being clinically significant resulting in permanently decreased vocal fold mobility. With each procedure, scar length increased by 1.0 mm and DGS decreased by 0.7 mm, reflecting a migration or decrease in DGS of 9.5% with each procedure with respect to initial DGS. Overall rates of glottic stenosis following operations were similar between LWEP and LWES cohorts, 7.6% and 7.5% respectively.

Conclusion

There appears to be a low risk of glottic involvement resulting from the LWE procedure in iSGS patients.

Level of Evidence

4 Laryngoscope, 2022

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