Chronic acidosis rewires cancer cell metabolism through PPARα signaling.

The mechanisms linking tumor microenvironment acidosis to disease progression are not understood. Here, we used mammary, pancreatic, and colon cancer cells to show that adaptation to growth at an extracellular pH (pHe ) mimicking acidic tumor niches is associated with upregulated net acid extrusion capacity and elevated intracellular pH at physiological pHe , but not at acidic pHe . Using metabolic profiling, shotgun lipidomics, imaging and biochemical analyses, we show that the acid adaptation-induced phenotype is characterized by a shift toward oxidative metabolism, increased lipid droplet-, triacylglycerol-, peroxisome content and mitochondrial hyperfusion. Peroxisome proliferator-activated receptor-α (PPARA, PPARα) expression and activity are upregulated, at least in part by increased fatty acid uptake. PPARα upregulates genes driving increased mitochondrial and peroxisomal mass and ß-oxidation capacity, including mitochondrial lipid import proteins CPT1A, CPT2 and SLC25A20, electron transport chain components, peroxisomal proteins PEX11A and ACOX1, and thioredoxin-interacting protein (TXNIP), a negative regulator of glycolysis. This endows acid-adapted cancer cells with increased capacity for utilizing fatty acids for metabolic needs, while limiting glycolysis. As a consequence, the acid-adapted cells exhibit increased sensitivity to PPARα inhibition. We conclude that PPARα is a key upstream regulator of metabolic changes favoring cancer cell survival in acidic tumor niches.

Sealing Ability of Different Obturating Techniques in Apically Separated Rotary Files: An In Vitro Study.

Aim: Testing whether two sealant systems (cold laterally compacted gutta-percha and Obtura II) can be used with extraction across two apically separated rotational nickel-titanium files was the primary objective of this study (RACE and K3). Materials and Methods: Both the positive and negative control teeth were randomly distributed among 62 mandibular premolars to create two groups of 30 each. Following the RACE and K3 approaches, four subgroups were created from the roots. Subgroups A1, B1, and A2, B2 (n = 10 each) were formed in the apical thirds of the canal at 3 mm from the tip. There was no division of instruments between groups A3, B3, B4, and A4. When it came to obturation, the Obtura II method was used for A2, A4, B2, B4, and A1, A3. A dye extraction process was employed to determine whether the specimens had been obliterated. Analysis of variance (ANOVA), Student t test (two-tailed, independent), and Leven's test were used to ascertain the values for each of the study groups. Results: Group A1 had a substantially lower leakage rate than group B1. Groups A2, B2 and A3, B3 had no statistically significant differences. Group A4 had a substantially lower leakage rate than group B4. Conclusion: Even when the cracked NiTi rotary system was not present, Obtura II-obturated groups had less leakage than the lateral condensation approach.

Efficacy of topical application of autologous platelet-rich plasma in adult tonsillectomy patients: a randomised control study.

OBJECTIVE: Tonsillectomy is a painful surgery performed in cases of recurrent tonsillitis. Application of platelet-rich plasma to diminish the pain and morbidity post-tonsillectomy is gaining importance. This study evaluated post-operative pain and morbidity after autologous platelet-rich plasma application on the tonsil beds during tonsillectomy. METHOD: Participants were randomised into group 1 (n = 28, peri-operative platelet-rich plasma intervention) and group 2 (n = 28, control). Post-tonsillectomy, patients were assessed (day 0, 1, 2, 3, 7 and 14) for pain, healing and time taken to return to normal activity. Data were analysed by independent t-test and chi-square test with p ≤ 0.05 as the significance level. RESULTS: A significant decrease in the mean pain score up to day 7 (p < 0.05) and tonsillar fossae healing on days 2 and 3 (p < 0.05) post-tonsillectomy was noted. The majority of the patients returned to their routine activities after a week post-tonsillectomy. CONCLUSION: Platelet-rich plasma application was effective in accentuating healing and reducing post-tonsillectomy pain and morbidity.

Comparison of flow-independent parameters for grading severity of aortic stenosis using intraoperative transesophageal echocardiography - A prospective observational study.

Introduction: Discrepancies have been reported in grading of severity of aortic stenosis. We propose to compare Aortic valve area by continuity equation, Dimensionless Index and Acceleration time/Ejection time in patients with documented severe aortic stenosis with normal left ventricular function by TEE after induction of anesthesia. This might give use insight about the best parameter we can rely on intra-operatively for decision making. Methodology: 60 patients with severe AS undergoing elective cardiac surgery were enrolled in our study. Post intubation trans-thoracic echocardiography (TEE) was performed and above mentioned parameters was noted. Results: 96.7 % of patients continued in severe AS category when AS was measured using AVA as echo parameter. So there is 3.3 % disparity. There was disparity in 13.3% of cases when DI was considered. And there was 43.3% disparity when AT/ET was considered. Conclusion: Perioperative grading of aortic stenosis continues to be a challenge for cardiac anesthesiologists. Multiple echocardiographic parameters have to be considered. We have found AVA and DI to have less disparity compared to AT/ET.

An unusual case of Aspergillus endocarditis of native aortic valve following ECMO.

Fungal endocarditis following Extracorporeal membrane oxygenation (ECMO) is rare and very rarely reported. Though rare it has a high mortality rate. A 49-year-old male patient who had venovenous ECMO presented with aortic valve endocarditis after 40 days. He underwent sutureless bioprosthehtic valve placement and debridement of abscess. Abscess fluid grew aspergillus species and was started on dual antifungal intravenous amphotericin and variconazole. He was discharged after 1 month with oral variconazole. Incidence of aseptic endocarditis (AE) has been on rise due to increase in invasive procedures. Blood culture is mostly sterile, and fever may be absent. Abscess debridement and aggressive dual antifungal treatment helped our patient in his road to recovery. In current era with increasing use of ECMO, newer rarer complications should be kept in mind. High index of suspicion is required for diagnosing fungal endocarditis after ECMO.

Comparison of grading of aortic stenosis between transthoracic and transesophageal echocardiography in adult patients undergoing elective aortic valve replacement surgeries: A prospective observational study.

Introduction: Intraoperative trans-esophageal echocardiography (TEE) has been found to underestimate severity of aortic stenosis (AS) compared to trans-thoracic echo (TTE). We conducted a prospective study comparing pre induction TTE and intra operative TEE grading of AS in patients posted for aortic valve replacement surgeries. Methods: Sixty patients with isolated AS who were undergoing aortic valve replacement were enrolled in our study. Baseline TTE was done and after induction of anesthesia, TEE was done. Mean gradient across aortic valve, peak jet velocity, aortic valve area (AVA) by continuity equation and dimensionless index (DI) were assessed in both. Results: Mean gradient decreased from 56.4 in TTE to 39.8 mm Hg in TEE leading to underestimation of AS in 74.5% of patients (P < 0.0). Mean of peak jet velocity also decreased from 500 in TTE to 386cm/s in TEE (P < 0.01). In 76 % of patients this led to reduction of AS grade from severe to moderate. Mean AVA was 0.67 cm2 in TTE and 0.69 cm2 in TEE. Though there was 0.02 cm2 increase, it was not statistically significant (P = 0.07). All the patients remained as severe AS in TEE. DI mean was 0.19 in both TTE and TEE (P = 0.14).It led to underestimation of severity in 6% of patients in TEE. Conclusion: Our study shows that AVA measurement by continuity equation and DI are reliable in grading aortic stenosis while performing intraoperative TEE. Mean gradient and jet velocity can be significantly reduced.

Apprising the diverse facets of Platelet rich fibrin in surgery through a systematic review.

CONTEXT: Comprehensive reviews on clinical applications of Platelet rich fibrin (PRF) in surgery are limited despite its extensive utilization resulting in a dearth of knowledge on its effectiveness. Hence this article focuses on shedding light to the various applications of PRF pertaining to surgery through a systematic review. OBJECTIVE: The systematic review is aimed at evaluating the value of PRF in different areas of surgery. DATA SOURCES: A systematic review of articles sourced from MEDLINE-pubmed (2008-2017(July)) was done. Additional articles were searched through GOOGLE SCHOLAR and SCIENCE DIRECT. Search terms such as Platelet rich fibrin; Platelet rich fibrin, surgery; Platelet concentrate; second generation concentrate; Applications of PRF in surgery were used. STUDY SELECTION: Systematic reviews, Randomized control trials, Pilot studies and Case reports were included. Non English articles, in-vitro and animal studies were excluded. DATA EXTRACTION: Independent sourcing of articles by 3 authors using a set of predefined criteria. DATA SYNTHESIS: Out of the 25 articles covering various surgical procedures that met the inclusion criteria, positive outcomes were noted in most. Although categorization into one specific type of study was not done, the overall success rate with PRF usage was 78%.No differences between test and control groups were observed in 2 studies and 3 studies showed no significant improvements with the usage of PRF. LIMITATIONS: The systematic review did not categorize the study designs while evaluating success rates which might be considered as a shortcoming as case reports were also included. CONCLUSIONS: The future propositions are vast and point towards innovative applications of this bio-material possibly in transplant and burn cases if a method of obtaining large amounts can be devised. However since we rely on evidence-based results, further long term studies are needed in distinct areas of applications to decisively prove its effectiveness.

Clinical evaluation of the efficacy of a GTR membrane (HEALIGUIDE) and demineralised bone matrix (OSSEOGRAFT) as a space maintainer in the treatment of Miller's Class I gingival recession.

BACKGROUND: Periodontal plastic surgical procedures aimed at coverage of exposed root surface have evolved into routine treatment modalities. The present study was designed to evaluate the effectiveness and predictability of using a collagen barrier along with a demineralized bone matrix in the treatment of recession defects in a single surgical procedure. MATERIALS AND METHODS: Seventeen patients with Miller's class I recession were treated with a combination of a collagen barrier used along with a bone graft and coronally advanced flap technique. Clinical parameters were recorded at baseline, 3 months, 6 months, and 9 months. RESULTS: The study showed a highly significant reduction in the recession depth (70.29 ± 21.96%) at the end of the study. This study showed that the use of this technique for recession coverage is highly predictable and highly esthetic root coverage can be obtained.