Liver‐specific Sirtuin6 ablation impairs liver regeneration after 2/3 partial hepatectomy

Abstract

Sirtuin 6 (Sirt6) is an NAD+‐dependent deacetylase that regulates central metabolic functions such as glucose homeostasis, fat metabolism and cell apoptosis. However, the tissue‐specific function of Sirt6 in liver regeneration remains unknown. Here, we show that liver‐specific Sirt6 knockout (Sirt6 LKO) impaired liver reconstitution after 2/3 partial hepatectomy, which was attributed to an alteration of cell cycle progression. Sirt6 LKO delayed hepatocyte transition into S phase during liver regeneration, as shown by the analysis of cell cycle‐related proteins and the immunostaining of Ki‐67 and 5‐bromo‐2‐deoxyuridine (BrdU). The delayed cell cycle in Sirt6 LKO mice was attributed to the disruption of m‐TOR and Akt activity, which is an important pro‐proliferation pathway in liver regeneration. Sirt6 LKO also reduced carbon tetrachloride (CCl₄)‐induced liver damage. Our results suggest that Sirt6 LKO impaired liver regeneration via delayed cell cycle and impaired m‐TOR and Akt activity.

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How is Endodontics taught? A survey to evaluate undergraduate endodontic teaching in dental schools within the United Kingdom

Abstract

Aim

To evaluate the delivery of undergraduate endodontic education in UK dental schools using an online survey and to compare the results with those of a previous paper‐based survey (Qualtrough & Dummer 1997). Aspects of delivery were also evaluated in comparison with Undergraduate Curriculum Guidelines of the European Society of Endodontology (de Moor et al. 2013).

Methods

An online version of an earlier paper‐based survey on undergraduate Endodontic education (Qualtrough & Dummer 1997) was created. Invitations to take part were sent via e‐mail to the undergraduate endodontic programme leads in the sixteen UK dental schools.

Results

The response rate was 94%. The current survey revealed greater convergence among dental schools than previously (Qualtrough & Dummer 1997) on methods of canal preparation, disinfection and filling. Improvements were also noted in staff: student ratios, the involvement of teachers with advanced endodontic training and a greater diversity of teaching methods; developments which align with the recommendations of ESE Undergraduate Curriculum Guidelines (de Moor et al. 2013). The majority of schools appeared to be teaching contemporary instrumentation methods and were recommending the application of calcium silicate cements. The exposure of students to advanced topics included in the ESE Undergraduate Curriculum Guidelines (de Moor et al. 2013) such as surgical endodontic treatment, root canal re‐treatment and the management of complex cases was mixed.

Conclusion

Undergraduate endodontic training in the UK has advanced in the last 20 years with more consistency between schools and more contemporary methods adopted.

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Effects of triethylene glycol dimethacrylate and hydroxyethyl methacrylate on macrophage polarization

Abstract

Aim

To evaluate the effects of hydrophilic dental resin monomers, triethylene glycol dimethacrylate (TEGDMA) and hydroxyethyl methacrylate (HEMA), on the polarization of a human monocyte cell line (THP‐1).

Methodology

THP‐1 cells were treated with resin monomers at non‐cytotoxic concentrations for 48 h and were analyzed for CD86 and CD206 expressions using flow cytometry. The cells were stimulated for polarization in the presence of resin monomers (co‐treatment), or after treatment with monomers (pre‐treatment). CD86 and CD206 mRNA in co‐treated cells was evaluated using quantitative real‐time polymerase chain reaction. The release of TNF‐α and TGF‐β by pre‐treated and co‐treated cells was assessed using enzyme‐linked immunosorbent assay. Morphological changes of macrophages during polarization were observed using bright‐field microscopy. One‐way analysis of variance was used for statistical analysis.

Results

TEGDMA (1 mmol/L) and HEMA (2 mmol/L) did not induce CD86 and CD206 expressions in THP‐1 cells but rather inhibited their expressions in the co‐treated cells. The inhibitory effects also appeared at the transcription level. However, the expression of surface markers was not affected by pre‐treatment with resin monomers. The release of TNF‐α and TGF‐β by M1‐ and M2‐stimulated cells, respectively, was suppressed by co‐treatment (P<0.05). Microscopic studies revealed that co‐treatment with resin monomers suppressed polarization‐associated morphological changes such as cell volume increase.

Conclusions

TEGDMA and HEMA inhibited macrophage polarization to both M1 and M2 at the transcription level, and the inhibitory effects disappeared upon the removal of resin monomers from the cell culture.

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Survival impact of treatment‐related time intervals in nasopharyngeal carcinoma in the United States

Objective

To determine if delayed or prolonged treatment‐related time intervals (TRTIs) was associated with survival in patients with nasopharyngeal carcinoma (NPC) undergoing curative‐intent concurrent chemoradiation (CCRT). The TRTIs investigated were duration of radiation treatment (RTd), time to radiation start (TTR), and time to chemotherapy start (TTC).

Methods

Observational cohort study using the National Cancer Database (NCDB). In this observational cohort study, 3,893 eligible patients with NPC were identified from the NCDB. Patients received CCRT of at least 66 grays and radiation treatment time of at least 40 days. Separate univariable Cox regression model was used to analyze overall survival (OS) as a function of TRTIs, as well as for Charlson/Deyo Score, tumor classification, node classification, histological type, ethnicity, age, sex, and facility type. Upon finding significance at P < 0.05, the multivariable Cox regression analysis with backward elimination was performed to yield the final prediction model. Results were considered statistically significant when P < 0.05.

Results

Radiation treatment was significantly associated with OS in the univariable analysis (hazard ratio: 1.006, 95% confidence interval = 1.004–1.008, P < 0.001). However, RTd was not related to OS in the multivariable analysis (P = 0.19). The TTR and TTC variables were not associated with OS in the univariable analysis (P = 0.88 and P = 0.88, respectively).

Conclusion

TRTIs were not independently associated with OS in this cohort of NPC patients in the NCDB. Future research into the association of TRTI with other disease outcomes, such as disease‐free survival and locoregional control, is needed.

Level of Evidence

NA. Laryngoscope, 2019

http://bit.ly/2DPZU9l

The evidence‐based preoperative assessment for the otolaryngologist

There is a narrow window of opportunity between surgical scheduling and the operative date to optimize patients for an elective surgical procedure. Traditionally, preoperative care has involved extended routine testing batteries with intermittent referrals for medical clearance. These traditions are costly, inefficient, and yield no clear reduction in perioperative morbidity and mortality. Evidence, which has evolved over the past decade, suggests that optimal preoperative care requires a patient‐centric, personalized, and often multidisciplinary approach. We present an up‐to‐date overview of this literature with a focus on the otolaryngologic surgical population. An algorithmic approach to preoperative patient assessment is also proposed in hopes of both optimizing patient outcome and streamlining routine clinical workflow. Laryngoscope, 2019

http://bit.ly/2MI7C8o

Survival impact of treatment‐related time intervals in nasopharyngeal carcinoma in the United States

Objective

To determine if delayed or prolonged treatment‐related time intervals (TRTIs) was associated with survival in patients with nasopharyngeal carcinoma (NPC) undergoing curative‐intent concurrent chemoradiation (CCRT). The TRTIs investigated were duration of radiation treatment (RTd), time to radiation start (TTR), and time to chemotherapy start (TTC).

Methods

Observational cohort study using the National Cancer Database (NCDB). In this observational cohort study, 3,893 eligible patients with NPC were identified from the NCDB. Patients received CCRT of at least 66 grays and radiation treatment time of at least 40 days. Separate univariable Cox regression model was used to analyze overall survival (OS) as a function of TRTIs, as well as for Charlson/Deyo Score, tumor classification, node classification, histological type, ethnicity, age, sex, and facility type. Upon finding significance at P < 0.05, the multivariable Cox regression analysis with backward elimination was performed to yield the final prediction model. Results were considered statistically significant when P < 0.05.

Results

Radiation treatment was significantly associated with OS in the univariable analysis (hazard ratio: 1.006, 95% confidence interval = 1.004–1.008, P < 0.001). However, RTd was not related to OS in the multivariable analysis (P = 0.19). The TTR and TTC variables were not associated with OS in the univariable analysis (P = 0.88 and P = 0.88, respectively).

Conclusion

TRTIs were not independently associated with OS in this cohort of NPC patients in the NCDB. Future research into the association of TRTI with other disease outcomes, such as disease‐free survival and locoregional control, is needed.

Level of Evidence

NA. Laryngoscope, 2019

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The evidence‐based preoperative assessment for the otolaryngologist

There is a narrow window of opportunity between surgical scheduling and the operative date to optimize patients for an elective surgical procedure. Traditionally, preoperative care has involved extended routine testing batteries with intermittent referrals for medical clearance. These traditions are costly, inefficient, and yield no clear reduction in perioperative morbidity and mortality. Evidence, which has evolved over the past decade, suggests that optimal preoperative care requires a patient‐centric, personalized, and often multidisciplinary approach. We present an up‐to‐date overview of this literature with a focus on the otolaryngologic surgical population. An algorithmic approach to preoperative patient assessment is also proposed in hopes of both optimizing patient outcome and streamlining routine clinical workflow. Laryngoscope, 2019

from #ORL via a.lsfakia on Inoreader http://bit.ly/2MI7C8o
via IFTTT