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Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for BrafV600E‐mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (TyrCreERT2/+; BrafLSLV600E/+; Ptenflox/flox) to Sirt5?/? knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5?/? mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for BrafV600E‐mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor.  相似文献   
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Purpose

This study examined whether hyperspectral stimulated Raman scattering (hsSRS) microscopy can detect differences in meibum lipid to protein composition of normal and evaporative dry eye subjects with meibomian gland dysfunction.

Methods

Subjects were evaluated for tear breakup time (TBUT), staining, meibum expression and gland dropout. Expressed meibum was analyzed using SRS vibrational signatures in the CH stretching region (2800–3050?cm?1). Vertex component analysis and K-means clustering were used to group the spectral signatures into four fractions containing high lipid (G1) to high protein (G4).

Results

Thirty-three subjects could be statistically analyzed using pooled meibum (13 with stable tear films (TBUTs?>?10?s) and 20 with unstable tear films (TBUTs?≤?10?s). Significant differences in meibum from subjects with unstable vs. stable TBUTs were found for the G1 fraction (medians 0.164 and 0.020, respectively; p?=?0.012) and the G2 fraction (medians 0.244 and 0.272, respectively; p?=?0.045). No differences were observed for the G3 and G4 fractions. Single orifice samples were not significantly different vs. pooled samples from the fellow eye, and eyelid sector samples (nasal, central and temporal) G2:G3 fractional components were not significantly different (p?=?0.449). Spearman analysis suggested a significant inverse correlation between G1 fraction and TBUT (R?=??0.351; p?=?0.045).

Conclusions

hsSRS microscopy allows compositional analysis of expressed meibum from humans which correlated to changes in TBUT. These findings support the hypothesis that hsSRS may be useful in classifying meibum quality and evaluating the effects of therapy.  相似文献   
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BackgroundComplications arising from laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are not insignificant and can necessitate additional invasive interventions or reoperations.ObjectivesIn this study, we identify early complications that result in nonoperative and operative interventions after LSG and LRYGB, the timeframe within which to expect them, and factors that influence the likelihood of their occurrence.SettingMulti-institutional database from across North America.MethodsData for this study were obtained from Metabolic and Bariatric Accreditation and Quality Improvement Program participant use files for 2015 and 2016. Statistical analysis was performed using STATA 15. Univariate analysis using Χ2 for categoric data and independent t test for continuous data was performed to determine between group differences. Multivariable logistic regression analysis was used to identify predictors of operative and nonoperative reinterventions.ResultsIn 2015 and 2016, 243,747 underwent LRYGB or LSG, of which 3013 (1.24%) required a second operative procedure and 1536 (0.63%) required an invasive but nonoperative intervention. Complications occurred in 5.48% of LRYGB patients and 2.28% of LSG patients, the most common of which was bleeding. LSG was associated with far fewer nonoperative and operative interventions (.85% versus 2.2%, respectively) than LRYGB (.67% versus 2.5%). Renal insufficiency, including dialysis dependency, was an important predictor of reoperations among bariatric surgery patients. This was also true of nonoperative interventions; however, history of pulmonary embolism, and use of therapeutic anticoagulation were marginally stronger predictors.ConclusionsIn a representative, multinational sample, operative and nonoperative interventions were half as likely among LSG patients compared with LRYGB; however, overall rates still remained low. These findings, in conjunction with new efficacy data demonstrating comparable long-term weight loss between LRYGB and LSG, provide further support for the safety, effectiveness, and cost efficiency of LSG.  相似文献   
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